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- Main article: Neural plasticity
Metaplasticity is a term originally coined by W.C. Abraham and M.F. Bear to refer to the plasticity of synaptic plasticity. Until that time synaptic plasticity had referred to the plastic nature of individual synapses. However this new form referred to the plasticity of the plasticity itself, thus the term meta-plasticity. The idea is that the synapse's previous history of activity determines its current plasticity. This may play a role in some of the underlying mechanisms thought to be important in memory and learning such as Long-term potentiation (LTP), Long-term Depression (LTD) and so forth. These mechanisms depend on current synaptic "state", as set by ongoing extrinsic influences such as the level of synaptic inhibition, the activity of modulatory afferents such as catecholamines, and the pool of hormones affecting the synapses under study. Recently, it has become clear that the prior history of synaptic activity is an additional variable that influences the synaptic state, and thereby the degree, of LTP or LTD produced by a given experimental protocol. In a sense, then, synaptic plasticity is governed by an activity-dependent plasticity of the synaptic state; such plasticity of synaptic plasticity has been termed metaplasticity. There is little known about metaplasticity, and there is much research currently underway on the subject, despite its difficulty of study, because of its theoretical importance in brain and cognitive science. Most research of this type is done via cultured hippocampus cells or hippocampal slices.
Historical discoveries
Hebbian Plasticity
The brain is "plastic", meaning it can be moulded and formed. This plasticity is what allows you to learn throughout your lifetime (Thiagarajan et al. 2007, p. 156); your synapses change based on your experience. New synapses can be made, old ones destroyed, or existing ones can be strengthened or weakened. The original theory of plasticity is called "Hebbian plasticity", named after Donald Hebb in 1949. A quick but effective summary of Hebbian theory is that "cells that fire together, wire together", together being the key word here which will be explained shortly. Hebb described an early concept of the theory, not the actual mechanics themselves. Hebbian plasticity involves two mechanisms: LTP and LTD, discovered by Bliss and Lomo in 1973. LTP, or long-term potentiation, is the increase of synapse sensitivity due to a prolonged period of activity in both the presynaptic and postsynaptic neuron. This prolonged period of activity is normally concentrated electric impulses, usually around 100 Hz. It is called "coincidence" detection in that it only strengthens the synapse if there was sufficient activity in both the presynaptic and postsynaptic cells. If the postsynaptic cell does not become sufficiently depolarized then there is no coincidence detection and LTP/LTD do not occur. LTD, or long-term depression, works the same way however it focuses on a lack of depolarization coincidence. LTD can be induced by electrical impulses at around 5 Hz. These changes are synapse specific. A neuron can have many different synapses all controlled via the same mechanisms defined here.
The earliest proposed mechanism for plastic activity is based around glutamate receptors and their ability to change in number and strength based on synapse activity. Glutamate has two main receptor types: AMPA and NMDA. These are named after drugs that bind to the receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate, respectively) however they all bind glutamate. When a glutamatergic synapse releases glutamate it binds to both the AMPA and the NMDA receptors. The AMPA receptors are ionotropic receptors that are responsible for fast synaptic transmission. In a nutshell the NMDA receptors evoke a response in the cell only when sufficient glutamate has been transmitted to cause that cell to depolarize enough to unblock the NMDA receptor. Sufficient depolarization in the membrane will cause the magnesium cation blockade in the NMDA receptors to vacate, thus allowing calcium influx into the cell. NMDA receptors are "coincidence" detectors. They determine when the presynaptic and postsynaptic neuron are linked in time via activity. When this occurs, NMDA receptors become the control mechanism that dictates how the AMPA and NMDA receptors are to be rearranged. The rearrangement of AMPA and NMDA receptors has become the central focus of current studies of metaplasticity as it directly determines LTP and LTD thresholds. There is large amounts of research focused on finding the specific enzymes and intracellular pathways involved in the NMDAR-mediated modulation of membrane AMPA receptors. Recent biochemical research has shown that a deficiency in the protein tenascin-R (TNR) leads to a metaplastic increase in the threshold for LTP induction. TNR is an extracellular-matrix protein expressed by oligodendrocytes during myelination (Bukalo, Schachner & Dityatev 2007, p. 6019).
In 1973, Terje Lømo and Tim Bliss first described the now widely studied phenomenon of long-term potentiation (LTP) in a publication in the Journal of Physiology. The experiment described was conducted on the synapse between the perforant path and dentate gyrus in the hippocampi of anaesthetised rabbits. They were able to show a burst of tetanic (100 Hz) stimulus on perforant path fibres led to a dramatic and long-lasting augmentation in the post-synaptic response of cells onto which these fibres synapse in the dendate gyrus. In the same year, the pair published very similar data recorded from awake rabbits. This discovery was of particular interest due to the proposed role of the hippocampus in certain forms of memory.
Synaptic States
Research in 2004 has shown that synapses do not strengthen or weaken on a sliding scale. There are discrete states that synapses move between. These states are active, silent, recently-silent, potentiated, and depressed. The states which they can move to are dependent on the state that they are in at the moment. Thus, the future state is determined by the state gained by previous activity. For instance, silent (but not recently-silent) synapses can be converted to active via the insertion of AMPARs in the postsynaptic membrane. Active synapses can move to either potentiated or depressed via LTP or LTD respectively. Prolonged low-frequency stimulation (5 Hz, the method used to induce LTD) can move an active synapse to depressed and then silent. However, synapses that have just become active cannot be depressed or silenced. Thus there is state-machine-like behavior at the synapse when it comes to transitions. However, the states themselves can have varying degrees of intensity. One active-state synapse can be stronger than another active-state synapse. This is, in theory, how you can have a strong memory vs. a weak memory. The strong memories are the ones with very heavily populated active synapses, while weak memories may still be active but poorly populated with AMPARs. The same research has shown that NMDA receptors themselves, once thought to be the control mechanism behind AMPA receptor organization, can be regulated by synaptic activity (Montgomery & Madison 2004, p. 744). This regulation of the regulation mechanism itself adds another layer of complexity to the biology of the brain.
Biochemical mechanisms
Two molecular mechanisms for synaptic plasticity (researched by the Eric Kandel laboratories) involve the NMDA and AMPA glutamate receptors. Opening of NMDA channels (which relates to the level of cellular depolarization) leads to a rise in post-synaptic Ca2+ concentration and this has been linked to long term potentiation, LTP (as well as to protein kinase activation); strong depolarization of the post-synaptic cell completely displaces the magnesium ions that block NMDA ion channels and allows calcium ions to enter a cell – probably causing LTP, while weaker depolarization only partially displaces the Mg2+ ions, resulting in less Ca2+ entering the post-synaptic neuron and lower intracellular Ca2+ concentrations (which activate protein phosphatases and induce long-term depression, LTD).[1]
These activated protein kinases serve to phosphorylate post-synaptic excitatory receptors (e.g. AMPA receptors), improving cation conduction, and thereby potentiating the synapse. Also, this signals recruitment of additional receptors into the post-synaptic membrane, and stimulates the production of a modified receptor type, thereby facilitating an influx of calcium. This in turn increases post-synaptic excitation by a given pre-synaptic stimulus. This process can be reversed via the activity of protein phosphatases, which act to dephosphorylate these cation channels.[2]
The second mechanism depends on a second messenger cascade regulating gene transcription and changes in the levels of key proteins at synapses such as CaMKII and PKAII. Activation of the second messenger pathway leads to increased levels of CaMKII and PKAII within the dendritic spine. These protein kinases have been linked to growth in dendritic spine volume and LTP processes such as the addition of AMPA receptors to the plasma membrane and phosphorylation of ion channels for enhanced permeability.[3] Localization or compartmentalization of activated proteins occurs in the presence of their given stimulus which creates local effects in the dendritic spine. Calcium influx from NMDA receptors is necessary for the activation of CaMKII. This activation is localized to spines with focal stimulation and is inactivated before spreading to adjacent spines or the shaft, indicating an important mechanism of LTP in that particular changes in protein activation can be localized or compartmentalized to enhance the responsivity of single dendritic spines. Individual dendritic spines are capable of forming unique responses to presynaptic cells.[4] This second mechanism can be triggered by protein phosphorylation but takes longer and lasts longer, providing the mechanism for long-lasting memory storage. The duration of the LTP can be regulated by breakdown of these second messengers. Phosphodiesterase, for example, breaks down the secondary messenger cAMP, which has been implicated in increased AMPA receptor synthesis in the post-synaptic neuron [citation needed].
Long-lasting changes in the efficacy of synaptic connections (long-term potentiation, or LTP) between two neurons can involve the making and breaking of synaptic contacts. Genes such as activin ß-A, which encodes a subunit of activin A, are up-regulated during early stage LTP. The activin molecule modulates the actin dynamics in dendritic spines through the MAP kinase pathway. By changing the F-actin cytoskeletal structure of dendritic spines, spines are lengthened and the chance that they make synaptic contacts with the axonal terminals of the presynaptic cell is increased. The end result is long term maintenance of LTP.[5]
The number of ion channels on the post-synaptic membrane affects the strength of the synapse.[6] Research suggests that the density of receptors on post-synaptic membranes changes, affecting the neuron's excitability in response to stimuli. In a dynamic process that is maintained in equilibrium, N-methyl D-aspartate receptor (NMDA receptor) and AMPA receptors are added to the membrane by exocytosis and removed by endocytosis.[7][8][9] These processes, and by extension the number of receptors on the membrane, can be altered by synaptic activity.[7][9] Experiments have shown that AMPA receptors are delivered to the synapse through vesicular membrane fusion with the postsynaptic membrane via the protein kinase CaMKII, which is activated by the influx of calcium through NMDA receptors. CaMKII also improves AMPA ionic conductance through phosphorylation.[10] When there is high-frequency NMDA receptor activation, there is an increase in the expression of a protein PSD-95 that increases synaptic capacity for AMPA receptors. This is what leads to a long-term increase in AMPA receptors and thus synaptic strength and plasticity.
If the strength of a synapse is only reinforced by stimulation or weakened by its lack, a positive feedback loop will develop, causing some cells never to fire and some to fire too much. But two regulatory forms of plasticity, called scaling and metaplasticity, also exist to provide negative feedback.[9] Synaptic scaling is a primary mechanism by which a neuron is able to stabilize firing rates up or down.[11]
Synaptic scaling serves to maintain the strengths of synapses relative to each other, lowering amplitudes of small excitatory postsynaptic potentials in response to continual excitation and raising them after prolonged blockage or inhibition.[9] This effect occurs gradually over hours or days, by changing the numbers of NMDA receptors at the synapse (Pérez-Otaño and Ehlers, 2005). Metaplasticity varies the threshold level at which plasticity occurs, allowing integrated responses to synaptic activity spaced over time and preventing saturated states of LTP and LTD. Since LTP and LTD (long-term depression) rely on the influx of Ca2+ through NMDA channels, metaplasticity may be due to changes in NMDA receptors, altered calcium buffering, altered states of kinases or phosphatases and a priming of protein synthesis machinery.[12] Synaptic scaling is a primary mechanism by which a neuron to be selective to its varying inputs.[13] The neuronal circuitry affected by LTP/LTD and modified by scaling and metaplasticity leads to reverberatory neural circuit development and regulation in a Hebbian manner which is manifested as memory, whereas the changes in neural circuitry, which begin at the level of the synapse, are an integral part in the ability of an organism to learn.[14]
There is also a specificity element of biochemical interactions to create synaptic plasticity, namely the importance of location. Processes occur at microdomains – such as exocytosis of AMPA receptors is spatially regulated by the t-SNARE Stx4.[15] Specificity is also an important aspect of CAMKII signaling involving nanodomain calcium.[16] The spatial gradient of PKA between dendritic spines and shafts is also important for the strength and regulation of synaptic plasticity.[3] It is important to remember that the biochemical mechanisms altering synaptic plasticity occur at the level of individual synapses of a neuron. Since the biochemical mechanisms are confined to these "microdomains," the resulting synaptic plasticity affects only the specific synapse at which it took place.
Theoretical mechanisms
A bidirectional model, describing both LTP and LTD, of synaptic plasticity has proved necessary for a number of different learning mechanisms in computational neuroscience, neural networks, and biophysics. Three major hypotheses for the molecular nature of this plasticity have been well-studied, and none are required to be the exclusive mechanism:
- Change in the probability of glutamate release.
- Insertion or removal of post-synaptic AMPA receptors.
- Phosphorylation and de-phosphorylation inducing a change in AMPA receptor conductance.
Of these, the first two hypotheses have been recently mathematically examined to have identical calcium-dependent dynamics which provides strong theoretical evidence for a calcium-based model of plasticity, which in a linear model where the total number of receptors are conserved looks like
where is the synaptic weight of the th input axon, is a time constant dependent on the insertion and removal rates of neurotransmitter receptors, which is dependent on , the concentration of calcium. is also a function of the concentration of calcium that depends linearly on the number of receptors on the membrane of the neuron at some fixed point. Both and are found experimentally and agree on results from both hypotheses. The model makes important simplifications that make it unsuited for actual experimental predictions, but provides a significant basis for the hypothesis of a calcium-based synaptic plasticity dependence.[17]
Short-term plasticity
Plasticity can be categorized as short-term, lasting a few seconds or less, or long-term, which lasts from minutes to hours. Short-term synaptic enhancement results from an increase in the probability that synaptic terminals will release transmitters in response to pre-synaptic action potentials. Synapses will strengthen for a short time because of either an increase in size of the readily releasable pool of packaged transmitter or an increase in the amount of packaged transmitter released in response to each action potential.[18] Types of short term plasticity include synaptic augmentation, depression, facilitation, or neural facilitation, and post-tetanic potentiation.
Synaptic augmentation
Synaptic augmentation is the increased efficacy of synapse lasting in the order of seconds (7 s often quoted). It has been found to be associated with increased efficiency with which action potentials cause release of vesicles containing transmitters.
Synaptic depression
Synaptic fatigue or depression is usually attributed to the depletion of the readily releasable vesicles. Depression can also arise from post-synaptic processes and from feedback activation of presynaptic receptors.[19] Heterosynaptic depression is thought to be linked to the release of adenosine triphosphate (ATP) from astrocytes.[20]
Long-term plasticity
Long-term depression and long-term potentiation are two forms of long-term plasticity, lasting minutes or more, that occur at excitatory synapses.[21] NMDA-dependent LTD and LTP have been extensively researched, and are found to require the binding of glutamate, and glycine or D-serine for activation of NMDA receptors.[20]
Long-term depression
Brief activation of an excitatory pathway can produce what is known as long-term depression (LTD) of synaptic transmission in many areas of the brain. LTD is induced by a minimum level of postsynaptic depolarization and simultaneous increase in the intracellular calcium concentration at the postsynaptic neuron. LTD can be initiated at inactive synapses if the calcium concentration is raised to the minimum required level by heterosynaptic activation, or if the extracellular concentration is raised. These alternative conditions capable of causing LTD differ from the Hebb rule, and instead depend on synaptic activity modifications. D-serine release by astrocytes has been found to lead to a significant reduction of LTD in the hippocampus.[20] A LTD was evidenced in 2011 for the electrical synapses (modification of Gap Junctions efficacy through their activity).[22]
Long-term potentiation
Long-term potentiation, commonly referred to as LTP, is an increase in synaptic response following potentiating pulses of electrical stimuli that sustains at a level above the baseline response for hours or longer. LTP involves interactions between postsynaptic neurons and the specific presynaptic inputs that form a synaptic association, and is specific to the stimulated pathway of synaptic transmission. Modification of astrocyte coverage at the synapses in the hippocampus has been found to result from the induction of LTP, which has been found to be linked to the release of D-serine, nitric oxide, and the chemokine, s100B by astrocytes.[20] LTP is also a model for studying the synaptic basis of Hebbian plasticity. Induction conditions resemble those described for the initiation of long-term depression (LTD), but a stronger depolarization and a greater increase of calcium are necessary to achieve LTP.[23]
Synaptic strength
The modification of synaptic strength is referred to as functional plasticity. Changes in synaptic strength involve distinct mechanisms of particular types of glial cells, the most researched type being astrocytes.[20]
Synaptic Tagging
Recent research (Young et al. 2006, p. 1784) has found a mechanism known as "synaptic tagging". When new receptor proteins are being expressed and synthesized they must also be transported to the synaptic membrane, and some sort of chemical messaging is required for this. Their research has shown that activation of cAMP/PKA signaling pathways is required for LTP induction due to its "tagging" nature. It was even shown that simple pharmacological activation of cAMP/PKA pathways was sufficient for the synapse to be tagged, completely independent of any sort of activity.
NMDA Receptors
The NMDA receptor is made up of three subunits: NR1, a variable NR2 subunit, and a variable NR3 subunit. Two NR2 subunits in particular have been the subject of intense study: NR2A and NR2B. The NR2B subunit not only is more sensitive to glutamate and takes longer to desensitize, but also allows more calcium entrance into the cell when it opens. A low NR2A/NR2B ratio is generally correlated with a decreased threshold of activation caused by rearing animals in light-deprived environments. This has been shown experimentally via light deprivation studies in which it was shown that the NR2A/B ratio declined. The threshold can be increased in some situations via light exposure. Studies of this nature were used to find the critical period for formation of the visual system in cats. This shifting ratio is a measurement of LTD/LTP threshold and thus has been posited as a metaplasticity mechanism (Philpot, Cho & Bear 2007, p. 495).
Glial cells not only provide structural and nutritional support for neurons, but also provide processing support via chemicals known as gliotransmitters. Gliotransmitters include glutamate, ATP, and, more recently, the amino acid D-serine. Once thought to be glycine itself, D-serine serves as a ligand in the glycine site of NMDARs. D-serine is synthesized by astrocytes and is heavily co-localized with NMDARs. Without D-serine there can be no NMDA-induced neurotoxicity, or almost any NMDA response of any kind. Due to this evidence it is clear that D-serine is an essential ligand for the NMDA receptors. An essential factor in this research is the fact that astrocytes will vary their coverage of neurons based on the physiological processes of the body. Oxytocin and vasopressin neurons will have more NMDA receptors exposed due to astrocyte activity during lactation than during normal functioning. This research took place mostly in cells from the hypothalamic supraoptic nucleus, or SON. Due to synaptic plasticity being almost completely dependent on NMDAR processing, dynamic astrocyte NMDAR coverage is by nature a metaplasticity parameter (Panatier 2006, p. 775).
Synaptic Homeostasis
Homeostatic plasticity manages synaptic connections across the entire cell in an attempt to keep them at manageable connection levels. Hebbian methods tend to drive networks into either a maximized state or a minimized state of firing, thus limiting the potential activity and growth of the network. With homeostatic mechanisms in place there is now a sort of "gain control" which allows these Hebbian methods to be checked in order to maintain their information processing abilities (Thiagarajan et al. 2007, p. 156). This kind of modulation is important to combat intense lack of neural activity, such as prolonged sensory deprivation (in this study in particular it is light-deprivation affecting visual cortex neurons) or damage caused by stroke. Synaptic scaling is a mechanism in place to hold synapse sensitivity at normalized levels. Prolonged periods of inactivity increase the sensitivity of the synapses so that their overall activity level can remain useful. Chronic activity causes desensitization of the receptors, lowering overall activity to a more biologically manageable level. Both AMPA and NMDA receptor levels are affected by this process and so the overall "weight" of each synaptic connection (refined by Hebbian methods) is maintained while still increasing the overall level of activity over the entire neuron. It has been shown that both the presynaptic and the postsynaptic neuron are involved in the process, changing the vesicle turnover rate and AMPA receptor composition respectively (Perez-Ontano & Ehlers 2005).
Recent research has found that the calcium-dependent enzyme CaMKII, which exists in an alpha and beta isoform, is key in inactivity-dependent modulation. A low alpha/beta ratio causes an increased threshold for cellular excitation via calcium influx and thus favors LTP (Thiagarajan et al. 2007, p. 156).
Endocannabinoid Metaplasticity
Research in 2004 has shown that endocannabinoid release from the postsynaptic neuron can inhibit activation of the presynaptic neuron. Type 1 canabbinioid receptors (CB1Rs) are the receptors on the presynaptic neuron responsible for this effect. The specific ligand is thought to be 2-arachidonyl glycerol, or 2-AG. This has mainly been found in GABAergic synapses and thus has been termed inihibitory long term depression (I-LTD). This effect has been found to be extremely localized and accurate, meaning the cannabinoids do not diffuse far from their intended target. This inhibition primes the synapses for future LTP induction and is thus metaplastic in nature (Chevaleyre & Castillo 2004, p. 871).
Neuronal adaptation mechanism
A new mechanism has been proposed that concerns the innate excitability of a neuron. It is quantified by the size of the hyperpolarization in mV due to K+ channels re-opening during an action potential. After any sort of learning task, particularly a classical or operant conditioning task, the amplitude of the K+ hyperpolarization, or "after hyperpolarization (AHP)", is greatly reduced. Over time this AHP will return to normal levels. This normalization does not correlate with a loss of memory but instead a loss of learning potential. (Zelcer et al. Grossberger, p. 460)
See also
- Activity-dependent plasticity
- BCM theory
- Hebbian theory
- Homeostatic plasticity
- Long-term potentiation (LTP)
- Metaplasticity
- Neural facilitation (Short-term plasticity)
- Non-synaptic plasticity
- Postsynaptic potential
- Spike timing dependent plasticity (STDP)
- Debanne D., Daoudal G., Sourdet V., and Russier M. 2003. Brain plasticity and ion channels. Journal of Physiology-Paris, 97(4-6), 403-414.
- Gaiarsa J.L., Caillard O., and Ben-Ari Y. 2002. Long-term plasticity at GABAergic and glycinergic synapses: mechanisms and functional significance. Trends in Neurosciences, 25(11), 564-570.
- Martin, S. J., Grimwood, S. J. and Morris, R. G. M., Synaptic plasticity and memory: and evaluation of the hypothesis , Annual Review of Neuroscience 23 (2000), 649-711.
- Pérez-Otaño I., Ehlers M.D. 2005. Homeostatic plasticity and NMDA receptor trafficking. Trends in Neurosciences, 28(5) 229-238. <http://www.psychiatry.wustl.edu/zorumski/journal%20club/Perez-Otano%20and%20Ehlers%209_23.pdf>
- Shi S.H., Hayashi Y., Petralia R.S., Zaman S.H., Wenthold R., Svoboda K., Malinow R. 1999. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science, 284(5421), 1811-1816. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10364548&dopt=Citation>
- Song, I., Huganir R.L. 2002. Regulation of AMPA receptors during synaptic plasticity. Trends in Neurosciences, 25(11), 578-589. <http://www.ingentaconnect.com/content/els/01662236/2002/00000025/00000011/art02270>
- ↑ Bear MF, Connors BW, and Paradisio MA. 2007. Neuroscience: Exploring the Brain, 3rd ed. Lippincott, Williams & Wilkins
- ↑ (2000). Postsynaptic protein phosphorylation and LTP. Trends in Neurosciences 23 (2): 75–80.
- ↑ 3.0 3.1 Haining, Z., Sia G., Sato T., Gray N., Mao T., Khuchia Z., Huganir R., Svodoba K. (2009). Subcellular Dynamics of Type II PKA in Neurons. Cell Press 62: 363–374.
- ↑ Seok-Jin, R., Escobedo-Lozoya Y., Szatmari E., Yasuda R. (2009). Activation of CaMKII in single dendritic spines during long-term potentiation. Nature 458 (19): 299–306.
- ↑ Shoji-Kasai, Yoko, Hiroshi Ageta, Yoshihisa Hasegawa, Kunihiro Tsuchida, Hiromu Sugino, Kaoru Inokuchi (2007). Activin increases the number of synaptic contacts and the length of dendritic spine necks by modulating spinal actin dynamics. Journal of Cell Science 120 (Pt 21): 3830–3837.
- ↑ Debanne, D., Daoudal G., Sourdet V., and Russier M. (2003). Brain plasticity and ion channels. Journal of Physiology, Paris 97 (4-6): 403–414.
- ↑ 7.0 7.1 Shi, S.H., Hayashi Y., Petralia R.S., Zaman S.H., Wenthold R., Svoboda K., Malinow R. (1999). Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284 (5421): 1811–1816.
- ↑ Song, I., Huganir R.L. (2002). Regulation of AMPA receptors during synaptic plasticity. Trends in Neurosciences 25 (11): 578–589.
- ↑ 9.0 9.1 9.2 9.3 Pérez-Otaño, I., Ehlers M.D. (2005). Homeostatic plasticity and NMDA receptor trafficking. Trends in Neurosciences 28 (5): 229–238. [dead link]
- ↑ Bear, M.F. (2007). Neuroscience: Exploring the Brain, 779, Lippincott Williams & Wilkins.
- ↑ Desai, Niraj S., Robert H. Cudmore, Sacha B. Nelson & Gina G. Turrigiano (2002). Critical periods for experience-dependent synaptic scaling in visual cortex. Nature Neuroscience 5 (8): 783–789.
- ↑ Abraham, Wickliffe, Warren P. Tate (1997). Metaplasticity: A new vista across the field of synaptic plasticity. Progress in Neurobiology 52 (4): 303–323.
- ↑ Abbott, L., Sacha B. Nelson (2000). Synaptic plasticity: taming the beast. Nature Neuroscience 3: 1178–1183.
- ↑ Cooper, Stephen J. (2005). Donald O. Hebb's synapse and learning rule: a history and commentary. Neuroscience and Biobehavioral Reviews 28 (8): 851–874.
- ↑ Kennedy, Matthew J., Ian G. Davison, Camenzind G. Robinson, and Michael D. Ehlers (2010). Syntaxin-4 Defines a Domain for Activity-Dependent Exocytosis in Dendritic Spines. Cell 141 (3): 1–12.
- ↑ Lee, Seok-Jin R., Yasmin Escobedo-Lozoya, Erzsebet M. Szatmari, and Ryohei Yasuda (2009). Activation of CaMKII in single dendritic spines during long-term potentiation. Nature 458 (7236): 299–304.
- ↑ Shouval, Harel Z., Gastone C. Castellani, Brian S. Blais, Luk C. Yeung, Leon N. Cooper (2002). Converging evidence for a simplified biophysical model of synaptic plasticity. Biological Cybernetics 87 (5-6): 383–391.
- ↑ Stephens, Charles S. (Jan 1999). Augmentation Is a Potentiation of the Exocytotic Process. Neuron 22 (1): 139–146.
- ↑ Zucker, Robert S. (Mar 2002). Short-term Synaptic Plasticity. Annual Review of Physiology 64: 355–405.
- ↑ 20.0 20.1 20.2 20.3 20.4 Achour, S. Ben (Mar 2010). Glia: The many ways to modulate synaptic plasticity. Neurochemistry International 57 (4): 440–445.
- ↑ Cite error: Invalid
<ref>tag; no text was provided for refs named
- ↑ J. S. Haas, B. Zavala, C. E. Landisman, Activity-dependent long-term depression of electrical synapses. Science 334, 389–393 (2011). [Abstract] [Full Text]
- ↑ Artola, Alain (1993). Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation. Trends in Neuroscience 16 (11): 480–487.
- Zelcer I, Cohen H, Richter-Levin G, Lebiosn T, Grossberger T, Barkai E (April 2006). A cellular correlate of learning-induced metaplasticity in the hippocampus. Cereb. Cortex 16 (4): 460–8..
- Abraham WC, Bear MF (April 1996). Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci. 19 (4): 126–30..
- Montgomery JM, Madison DV (December 2004). Discrete synaptic states define a major mechanism of synapse plasticity. Trends Neurosci. 27 (12): 744–50..
- Pérez-Otaño I, Ehlers MD (May 2005). Homeostatic plasticity and NMDA receptor trafficking. Trends Neurosci. 28 (5): 229–38..
- Chevaleyre V, Castillo PE (September 2004). Endocannabinoid-mediated metaplasticity in the hippocampus. Neuron 43 (6): 871–81..
- Philpot BD, Cho KK, Bear MF (February 2007). Obligatory role of NR2A for metaplasticity in visual cortex. Neuron 53 (4): 495–502..
- Thiagarajan TC, Lindskog M, Malgaroli A, Tsien RW (January 2007). LTP and adaptation to inactivity: overlapping mechanisms and implications for metaplasticity. Neuropharmacology 52 (1): 156–75..
- Young JZ, Isiegas C, Abel T, Nguyen PV (April 2006). Metaplasticity of the late-phase of long-term potentiation: a critical role for protein kinase A in synaptic tagging. Eur. J. Neurosci. 23 (7): 1784–94..
- Bukalo O, Schachner M, Dityatev A (May 2007). Hippocampal metaplasticity induced by deficiency in the extracellular matrix glycoprotein tenascin-R. J. Neurosci. 27 (22): 6019–28..
- MacDonald JF, Jackson MF, Beazely MA (April 2007). G protein-coupled receptors control NMDARs and metaplasticity in the hippocampus. Biochim. Biophys. Acta 1768 (4): 941–51..
- Panatier A, Theodosis DT, Mothet JP, et al. (May 2006). Glia-derived D-serine controls NMDA receptor activity and synaptic memory. Cell 125 (4): 775–84..
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text:
I'm making the maps for an module a poster on the Steve Jackson Games GURPS forum is making, and I decided to post them here, so I could learn a little from the masters.
Basically, it was made in GIMP via the Dungeon Map Maker script, but I also used the Fractalize path (for the cave). I've made 3 versions, one gridless for Virtual tabletop programs, one with a square grid (1 square=1 yard) and one with an hex grid (1 hex=1 yard). There are 6 more levels though...
Distributed under Creative Commons Attribution-Share Alike 3.0 Unported
Also, not it needs furniture/doors/porticulises. Does anyone know about a set of map symbols under a license compatible with CC-BY-SA?

subset: commoncrawl


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There are several types of bachelor's degree programs awarded by universities, and an accredited online bachelor's degree is no different. By far the most common are the Bachelor of Arts (BA) and Bachelor of Science (BS) degrees, though which you receive depends partly upon your field of study and partly upon your particular educational institution.


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The Foreign Affairs Committee of the Norwegian Parliament is visiting Tanzania. The tour, which began on September 20, this year, is expected to end tomorrow.
According to a statement issued by the Norwegian Embassy in Dar es Salaam recently, the visiting lawmakers would discuss how Norway could become a better partner in promoting economic growth and development of Tanzania in a way that avoids further pressure on the environment, as well as in supporting efforts to deal with climatic changes.
"Tanzania is already experiencing visible effects of climate change such as prolonged drought, desertification, flooding and changing rainfall pattern which is affecting farming and pastoral activities," read the statement in part.
It said the country's future economic growth and development depended on finding a way to mitigate and adapt to the effects of climate change.
"I am very pleased to welcome the MPs to Tanzania. Climate change threatens future economic growth and development. Norway can be a partner in finding solutions, including access to sustainable energy sources, combating deforestation and improving sustainable agriculture," said Ambassador Ingunn Klepsvik.
The envoy said Tanzania's carbon dioxide emissions were estimated at 100 million tonnes every year.
"Deforestation is the largest contributing factor to this. Norway has agreed to supports efforts to Reduce Emissions from Deforestation and Forest Degradation (REDD) in Tanzania with USD 100 million over five years. The programme recognises services provided by living forests," she said, adding:
"Such services are at global level emission reductions and at local level improved water resources management and livelihood for communities."
The Norwegian legislators would among others meet villagers from Kolo Hills in Kondoa district who benefit from the programme.
In addition to official meetings in Dar es Salaam, the seven Norwegian parliamentarians would visit the power plant at Kihansi (which was built with support from Norway and other partners), forest plantations in Mufindi and spend one day in Arusha National Park.
"The group of seven parliamentarians has members from four different Norwegian political parties. They are all members of the Standing Committee on Foreign Affairs and Defence. Three of the parliamentarians represent the coalition government in Norway, while four come from the opposition parties. The visit to Tanzania is part of a mission to Ghana and Tanzania," said the embassy statement.


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Frequently Asked Questions
Along with academic training, another important aspect of your education is hands-on career development. It is our mission to assist you with these career-building opportunities. Therefore, the Office of Career Services offers a wide range of services for students including:
- referrals to cooperative education opportunities;
- career fair events;
- internet resources; and
- assistance with job search strategies for graduates.
We hope that you will take a few moments to review the services we offer to Volunteer State Community College students. If you have questions, or would like to visit us, we are located in the Annex 100 Building, Room 102.
- What does the Office of Career Services and Community Engagement have to offer?
The Office of Career Services and Community Engagement offers a wide range of services for students including referrals to cooperative education opportunities; part-time, ; career fair events; internet resources; and assistance with job search strategies for graduates.
- When should I start visiting the Office of Career Services and Community Engagement?
The Office of Career Services and Community Engagement welcomes students from their first days on campus. Even though the first few months of college can be quite busy and Career Services is not the first office students think to visit, students seeking part-time positions will need to register with the office as soon as possible.
- I am confused about what I should major in, where can I go to receive assistance?
The Testing Center is actually a separate office. Students who have not yet declared an academic major or who have second thoughts about the one they have initially chosen should schedule an appointment for interest testing and/or follow-up activities.
- Should I work while I'm in school?
A part-time job is an excellent way for students to build their resume and work on their transferable skills, such as organization, communication, time-management, and leadership.
- Is a part-time job like a cooperative work experience and how important is it?
Part-time jobs and co-ops do vary in some ways. Typically, part-time jobs include positions such as wait staff, administrative help and retail sales. Both part-time jobs and co-ops are ways that work experience can be obtained, although a co-op typically offers a student experience that is more closely related to full-time jobs after graduation.
In addition, co-ops tend to be much more structured, include more supervision and training, and are designed specifically for college students. With their structured professional environment, co-ops assist students in determining if they want to continue long term in that field. In some cases a full-time job offer may be extended after completing a cooperative work experience.
Remember both part-time employment and cooperative work experiences can provide valuable learning experiences. They both allow students to gauge their interest in a particular field. In addition they offer opportunities to build transferable skills. A student who has gained related work experience is going to be much more marketable and valuable to employers, compared to those students who have not gained related work experience. Participating in a co-op or finding a part-time related job will benefit you as you prepare to graduate and seek full-time employment.
- When is the best time to look for a cooperative work experience?
Students must be 70 percent complete with their degree program in order to complete a cooperative work experience. The co-op search is a process that requires pre-planning on the part of the student.
- How can I meet potential employers for full-time job opportunities?
There are many ways that students can meet potential employers. The Office of Career Placement and Cooperative Education holds two career fairs each year: a Fall Job Career Fair and a Spring Job Career Fair. In addition to the career fairs, the office hosts a career week during the spring semester, and a number of employers participate in on-campus recruiting. Students are encouraged to view the on-campus recruiting schedule. All full-time jobs received by the Office of Career Placement and Cooperative Education are listed for students to view on the Job Listings link.
- What do employers look for in potential employees?
Employers look for employees that have a number of skills. The most important skills are communication (verbal and written), honesty/integrity, teamwork, interpersonal, and motivation/initiative. In addition, they look at the student's academic background (major and GPA), appearance, their comfort level during the interview and their previous experiences (part-time job/co-op).


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Clatsop and Tillamook County
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Benton CountyMarion CountyPolk County
Benton CountyMarion CountyPolk County
Statewide SPIS Maps (Includes sites both On-State and Off-State Highways)
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Oregon has made a major effort to emphasize safety in all projects. The Safety Investment Program (SIP) of the Statewide Transportation Improvement Program (STIP) provides separate funding to address safety issues on preservation projects. In addition, safety considerations are identified in all projects involving the governor and the legislature.
NOTE: The SIP Program was discontinued after 2012.
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Heidelberg University kicked off its annual observance of Martin Luther King Jr. Day with an outstanding representation of King's philosophy of service to others. On Monday, more than 200 students and about 25 faculty and staff members fanned out into the community to perform service at 28 locations.
"We did a lot of good, but not enough. It was a great day but there are more great days needed," said HU President Rob Huntington in his welcoming remarks on Tuesday as the university came together to formally celebrate the work and words of MLK.
The president posed the question, "Why are we here?"
"Because we're not satisfied," he answered.
Because 45 years after King's assassination, civil rights progress has been made, but not enough.
"In Dr. King's life, I believe in essence, what he was trying to get us to grasp is that however we move forward, we still have a way to go."
Citing King's words, he added, "No, no, we are not satisfied, and we will not be satisfied until justice rolls down like waters and righteousness like a mighty stream."
"That's why we're here."
Heidelberg reached out across town to Tiffin University's Dr. Sharon Perry-Nause to give a call to action during the celebration. Perry-Nause is the director of institutional diversity and assistant professor of management.
Perry-Nause focused on the topics of humanity and the humanities as they related to King and her own personal journey. As a child in a single-parent home, a college education seemed unreachable.
"I'm all about education. I totally believe it can change your life because it changed mine," she said. People in her life showed her the path to meet her educational goals. She went on to earn her Ph.D. degree, and said she feels a sense of responsibility to give back.
"No matter what type of college or university or community college, I have an obligation to help individuals reach their goals," she said. "If we can help individuals get through college, allow college to be more accessible, then actually, we are helping society as a whole."
Returning to her theme of the humanities, Perry-Nause said the stories, words and experiences within connect our lives in ways that King would desire.
As part of the ceremony, HU presented the annual President's Service Award to Joe Worthy, '08 (in absentia). As a student, Worthy was active with Black Student Union and other causes such as encouraging students to vote. He has mentored youth in the Boston area and currently is the Ohio director of youth leadership and organizing for the Children's Defense Fund in Cleveland.
As is customary, the Heidelberg Concert Choir, under the direction of Dr. Greg Ramsdell provided a stirring performance of "The King of Love My Shepherd Is." The program concluded with those in attendance joining to sing "Lift Every Voice and Sing" a sending forth by Campus Minister Paul Sittason Stark.


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this wiki
Palkia (Japanese: パルキア Parukia) is a Water/Dragon-type Legendary Pokémon. Palkia is the Spatial Pokémon, and serves a the Version Mascot for Generation IV's Pokémon Pearl. Palkia is among two Pokémon to have only a weakness to Dragon-type moves. It is the rival of Dialga and Giratina.
Palkia is a very large, bipedal Water/Dragon Pokémon. The majority of its body has a light pink-grey-white coloring with linear sections on its body being purple. Its arms and shoulders are covered by large armour plates, and each hand holds five nails. The round plates on its shoulders each have a large pearl in the center, representing its affiliation to Pokémon Pearl. On Palkia's back are wings, which are seemingly not used for flight as Palkia appears to levitate.
Special Abilities
Palkia has the ability Pressure, which causes opponents PP usage to be doubled for every successful hit. In addition to this, Palkia has been described as having the ability to warp space creating ways for it to live and travel in a different dimension. When Palkia appears in Pokémon Pearl, it bends space and changes the looks of things around it. This effect is similar to Giratina's effect in Pokémon Platinum. It is said that Palkia and Dialga were never supposed to meet.
In the Manga
In the Pokémon Adventures Manga, Cyrus was controlling Palkia.
In the Anime
Palkia's first appearances were in the Diamond & Pearl series's Dragon Trilogy. It was first shown, along with Dialga and Darkrai, in The Rise of Darkrai, where it fought with Dialga and nearly destroyed Alamos Town. It was shown in a flashback in Giratina and the Sky Warrior, and finally, in Arceus and the Jewel of Life, alongside Dialga and Giratina, started a battle which awoke an ancient power. The Dragon Trio (Palkia, Dialga, and Giratina) seem to have equal power. Although Palkia fought Dialga in The Rise of Darkrai, they now seem to understand and accept each other, like when Palkia saved Dialga from the waterspout Arceus made, or when they fought alongside each other against Arceus.
Statues of Palkia have appeared in A Secret Sphere of Influence!, Journey to the Unown!, Losing Its Lustrous!, Double Team Turnover!, Steeling Peace of Mind!, Saving the World From Ruins!, and Bagged Then Tagged!. Palkia made its anime debut in The Battle Finale of Legend!, although a silhouette of Palkia appeared in All Dressed up with Somewhere to Go. This could possibly be the one from the dragon trio movies since there's only one Palkia in existence.
Palkia also makes a cameo in the Together and Diamond and Pearl openings.
Palkia does not evolve.
Game Info
Palkia is described as a deity/god in Sinnoh-region creation mythology, and is said to live in a gap in a parallel spatial dimension. Referred to as the Spatial Pokémon, Palkia has the ability to distort space. Palkia also has the power to create new dimensions. In Rise of Darkrai, he was shown to be able to trap dimensions into another one. In Mystery Dungeon, Palkia is referred as a male.
Main Series
In Pokémon Pearl
- After chasing and battling Team Galactic countless times through Mt. Coronet, the player ends up on the summit of the mountain, where lies a place known as Spear Pillar. When there, you see Cyrus, who uses the Red Chain he crafted from the powers of legendary Pokémon Uxie, Azelf, and Mesprit to call up and control Palkia, in order to change the world to Cyrus's liking. After defeating Cyrus, the Palkia seemingly awaits to battle the player. When the player battles is it, the player has the chance to catch the Palkia. If the Palkia is defeated before caught, there is another chance to encounter the Pokémon; after defeating the elite four and Cynthia.
In Pokémon Diamond
Palkia is not encountered in Pokémon Diamond, but can be registered into the PokéDex, and/or traded from Pokémon Pearl.
In Pokémon Platinum
Palkia, along with Dialga can be encountered both at level 70 after the player defeats the game. To encounter these two powerful Pokémon, the player must possess the Lustrous Orb for Palkia, and the Adamant Orb for Dialga. These items can be obtained from an old lady after beating the game. When the items are in possession, the player can go to Spear Pillar, where s/he can use the orbs to summon the legendaries for battle.
In Pokémon Mystery Dungeon
In Pokémon Mystery Dungeon: Explorers of Time & Explorers of Darkness
You and your partner are having a good night sleep. Suddenly, the ground starts to shake. A blinding light appears for a split second, then clears, revealing Palkia. Palkia takes you to Spacial Rift and pushes you off a cliff of 40,000 ft. but you and your partner somehow survive the fall.
- At the end you will face Palkia. Palkia is a nasty encounter if your a Fire type Pokémon. When you defeat him he will get trapped in nightmare (Exactly the same way Azurill does.). You enter it and as soon as Cresselia prepares to destroy you, another Cresselia (which the other is completely unaware of.) appears. You, your partner and Palkia look back and forth a few times, confused. Creselia 2 blasts light at the other one, revealing Darkrai underneath. After the final battle, Darkrai tries to escape. Fortunately, Palkia appears and shatters the dimensional hole while Darkrai was half way through as revenge for using him.
In Super Smash Bros. Brawl
Palkia along with the chance of two other Pokémon, Dialga and Cresselia, will appear in the Spear Pillar stage. When Palkia appears on the stage, it will distort the level in a variety of ways. In addition, it will also fire a number of beams causing damage to hit players.
- Palkia will appear when the sky becomes purplish pink.
|Spear Pillar (Pearl only)
|Spear Pillar(Get the Lustrous Orb)
|Shinto Ruins (requires event Arceus)
|One (Event)
Side Game Locations
|Explorers of Time & Explorers of Darkness
|Spacial Rift (Bottom)
|Pokémon Ranger: Shadows of Almia
|Hippowdon Temple (during mission)
|Pokémon Rumble
|Ticket for releasing Blastoise, Gyarados, Empoleon, Dragonite and Garchomp
Pokédex Entries
By Level-Up
|Gen. IV
|Scary Face
|Water Pulse
|Dragon Claw
|Spacial Rend
|Heal Block
|Earth Power
|Aqua Tail
|Aura Sphere
By Move Tutor
Draco Meteor. Lower's user's SP. Attack two stage.
Fury Cutter
Aqua Tail
Ancient Power
Earth Power
|Platinum, HeartGold and SoulSilver
|File:P sprite.png
|File:Spr 4p 484.png
|File:Shiny Pearl.png
|File:Spr 4p 484 s.png
- In the anime, Palkia's roar is a mix of Godzilla and King Ghidorah's (both monsters from the Godzilla franchise) roars, plus Boga from Star Wars Episode III: Revenge of the Sith.
- Palkia is the only member of the creation trio that does not have a unique type combination, because Kingdra is also Water/Dragon.
Name Origin
- The name "Palkia" is partly derived from the word "Paru", meaning pearl in Japanese. Since the Japanese language possesses only one liquid consonant, which is the equivalent of the English language /l/ and /r/, the "r" in paru can be used as an "l", creating Palkia when romanized.
- Pokémon.com Pokédex
- Serebii.net Pokédex data
- Legendary Pokémon data
- The Pokémon Database
- Pokémon Dream Pokédex data
- Psypokes Psydex data


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On the upside
Shares of sporting goods retailer Cabela's (NYSE: CAB) soared after President Obama detailed proposals for stricter gun control.
Opko Health (NYSE: OPK) chief executive Phillip Gamma Frost, M.D. purchased 20,000 shares of company stock.
On the downside
Motley Fool noted that Celsion (Nasdaq: CLSN) will likely use all of its cash in 2013. UBS downgraded Ironwood Pharmaceuticals (Nasdaq: IRWD) to a Sell rating.
Shares of Hovnanian Enterprises (NYSE: HOV) fell as homebuilder confidence held steady in January.
In the broad market, declining issues outpaced advancers by a margin of nearly 5 to 4 on the NYSE and by nearly 3 to 2 on Nasdaq. The broader S&P 500 index held steady at 1472.


text: Everyday chopping, slicing and mincing are faster and more efficient when you use this classic Japanese-style knife. Echoing the shape of a traditional cleaver, the wide, ultra-sharp blade is ideal for prepping everything from fresh vegetables, fruits and herbs to meats and poultry. Hollow-ground indentations on the blade reduce friction and minimize sticking. The wide blade is also great for scooping prepped ingredients into your soup pot or salad bowl.


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Need Help? Call 877.812.6235
Chef'n Butter Maker
- Summary
Make your own butter at home in minutes with just cream and salt—it's easy with this simple jar-style "churn." Homemade butter lets you use the quality ingredients of your choice and ensures the freshest, clearest flavor. Add herbs or garlic to make delicious flavored butters, too.
- Simply pour in cream, bring to room temperature, shake for several minutes, then strain.
- BPA-free plastic and silicone construction.
- Jar bottom doubles as a ramekin for serving.
- One cup heavy cream yields 8 oz. butter.
- Make lemon herb butter for fish or vegetables, honey butter for homemade rolls or roasted garlic butter for topping a steak.
- Dimensions & More Info
- 5" high; 1-cup cap.
- Made in China.
- Use & Care
- Dishwasher safe (top rack).
- Shipping
Shipping Information
This item is shipped from our warehouse by UPS to arrive within five business days of our receiving your order.
Shipping Rates
The shipping rate varies depending on your order total and shipping destination. View Shipping Options and Charges.
Next Day Delivery
For an additional charge of $17.50 per address, we can expedite delivery to most destinations. This service is not available for some oversize items, items shipped directly from the supplier (including perishable and custom-manufactured items), out-of-stock items and items to be shipped outside the contiguous 48 states.
Orders received by 9:00 p.m., Eastern time, Monday through Thursday will arrive the next business day; orders placed Friday through Sunday will arrive on the following Tuesday.
Return Policy
At Williams-Sonoma, we take great pride in the quality and craftsmanship of our products. Attention to design, materials, safety and construction are our priority. Upon receipt, please inspect your purchase and notify us of any damage; we will arrange for a prompt replacement.
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For all cutlery returns (knife sets, single knives, cutting boards, knife sharpeners, and knife storage) please contact us at 888.922.4108 to initiate the return.
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For returns of items purchased from your Williams-Sonoma Gift Registry, we will gladly provide a refund or exchange for the merchandise within 90 days of your event or within 90 days of purchase, whichever date is later. View Full Return Policy.


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Authorities say a 23-year-old Durango man was killed and another was injured when their backcountry skiing group was caught in an avalanche near Silverton.
The Durango Herald reports Peter Carver died Saturday afternoon while skiing north of Gladstone outside the boundaries of Silverton Mountain Ski Area. One member of the group suffered a possible broken femur, while a third escaped the slide without serious injuries.
Forecasters with the Colorado Avalanche Information Center are expected to visit the scene to determine what triggered the avalanche, which occurred on land owned by the Bureau of Land Management.
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London 2012 - Rigoberto Uran of Colombia keeps a wary eye on Alexandr Vinokurov. The veteran cyclist from Kazakhstan and the Colombian surprise those who expected a bunch sprint finish.
London 2012 - The peloton fly past the Victoria Memorial and Buckingham Palace during the men's cycling road race.
London 2012 - The official referee car for the women's cycling road race zooms past Buckingham Palace.
London 2012 - A group of three riders charge hard under a partly cloudy London sky.


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Kenny G started playing saxophone when he was 10 years old, and today he is one of the most widely recognized jazz musicians in the world. In addition to his arsenal of solo albums, the GRAMMY Award winner has collaborated with numerous music legends, including Whitney Houston, Frank Sinatra, and Andrea Bocelli. When this celebrated performer brings his talents to a venue near you, be sure to secure your Kenny G tickets through Vivid Seats. You can reach our talented customer service team seven days a week by calling 866.848.8499 or clicking on the Live Chat link.
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Also known as slow cooker lasagna as crock pot is a registered trademark. I do have a Rival Crock pot so I guess I can use the word.
Crock Pot Lasagna
28 ounces of sauce- I used my roasted tomatoes to make a meat sauce (recipe follows)
1 box of lasagna noodles- uncooked and broken to fit the crock
2 cups bechamel sauce (recipe follows)
1 1/2 cups ricotta cheese- full fat please!
1 egg-beaten
2 cups shredded mozzarella cheese
1/2 cup grated parmesan cheese
Spray crock pot with non-stick spray.
Mix ricotta cheese with egg and 1 teaspoon parsley.
Have all ingredients ready and begin by layering sauce then noodles, breaking to fit as needed.
Spread a little of the ricotta mixture on each noodle, cover with a ladle or so of bechamel sauce, then the meat sauce and a sprinkling of mozzarella.
You can also sprinkle some grated parmesan at this point too. Layer until you have only a little of the sauces left and finish the top layer with noodles, sauces and cheese. Cook on low 4-5 hours. Turn off and let sit for 15 minutes or so. If you want the top to crisp up and you have a removable crock, you can put the crock under the broiler for about 5-10 minutes or until browned.
Here it is after 2 hours of cooking on low. I have to leave and cook it the rest of the time at the party I am taking it to.
So the verdict is in, this was a huge hit at the fall party today. I barely got a serving and it was one of the first dishes to be emptied. Many who tried it said it was delicious and my boys ate it as well. So it cooked a total of 4 hours on low, which is like high in my crock pot. Enjoy!
**I made this ahead of time the night before.**
Here are the two sauces:
Bechamel sauce
2 1/2 tablespoons butter
2 tablespoons flour
2 cups of milk
1 teaspoon nutmeg
salt and pepper
1/4 cup grated Parmesan can omit if you want
Melt butter on medium heat. Whisk in flour and cook for 2 min. or so whisking the whole time. Slowly add in the milk, stirring or whisking entire time. Bring to a boil, lower heat and add in seasonings. Let cook a few more minutes, stirring occasionally. Cool a bit.
Roasted tomato meat sauce
1 recipe of roasted tomatoes with onions and garlic ( I added a quartered onion in the pan of tomatoes. I also roasted for 30 minutes on 425 to make it faster)
1-2 cups water
1 pound browned ground meat-I used turkey because that is what I had on hand
1 teaspoon each of dried oregano, basil and parsley
salt and pepper to taste
After the tomatoes have cooled, add the water into the food processor as you pulse.
I did not strain the sauce.Add tomatoes to the pot of browned meat and add seasonings. Let simmer for 30 minutes or so. Let cool a bit before using in the lasagna.


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RIP-IT Bat Backpack (Equipment Not Included)
|Eligible for Free Shipping on Orders $39 or More! (see promotion details)
|Members of The League get 5% back when you spend $100! (see promotion details)
Product Details
The RIP-IT bat backpack can hold up to two bats; this means you can carry your game bat and your cage bat all the time! They're held in the back (not on the side), making them easier to carry. It also features enough room for a helmet with face guard, fielder's mask, fielding glove, batting gloves, cleats, bats, and more. Keep all your stuff together in one place so you always have it when you need it.
- 600D nylon construction
- Holds up to two bats
- Boasts enough room for a helmet with a face guard, a fielder's mask, fielding glove, batting gloves, cleats, bats, and more
- Padded shoulder straps
Product Recommendations
Product Reviews
Reviewed by 1 customer
- Comfortable
- Holds A Lot
- Holds Gear Well
- Protective
- Stylish
- Heavy
- none
Best Uses
- Baseball
- Games
- Practice
Comments about RIP-IT Bat Backpack (Equipment Not Included):
I use this on a daily basis for baseball games and practices.
- Was this a gift?:
- No


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Fire crews responded to a mobile home fire late Wednesday night in the Cimarron Hills area. Nobody was hurt, but the entire home is destroyed.
We're told the call came in around 11:30 p.m. One person was living in the mobile home, but was able to escape the fire without injuries.
The fire was on Western Drive. near Peterson Road. Several neighbors say fire and smoke was billowing out of the windows when firefighters arrived.
Fire crews say they knocked down the fire quickly, but remained on scene all night long until Fire investigators arrived on the scene after 7a.m. this morning.
The cause of the fire is still under investigation, but neighbors do believe it is suspicious. 11 News is working with fire investigators to bring you the newest information as they gather it.
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A Dual Shipping Container Home
Posted by Erin | Filed under Design Tips, House Tours, Inspiration, Musings, Solutions
Sure, you've seen shipping containers as homes before, but have you seen two shipping containers inside one home?
San Francisco-based couple Jeff Wardall and Claudia Sagan tackled their industrial loft by adding two shipping containers to the interior – nearly doubling the function of the space.
Lofts are rarely blessed with the promise of privacy, so adding in a designated shipping container for both a guest bedroom and home office was a genius move.
The pair can now live, work and host in peace, while still maintaining the industrial aesthetic of their beloved loft. So smart, yes?
Tell me, would you install shipping containers inside your home? Or is the look a bit too modular for your taste? Spill it in the comments below!
Image Credits: Drew Kelly via Inthralld
Tags: home storage, industrial loft, shipping container home, shipping containers


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Date(s) - 04/09/2013–04/13/2013
All Day
Event Description
Memphis College of Art juniors and seniors in Assistant Professor Elizabeth Brown's Sustainable Sculpture: Works in Cardboard class will showcase their outdoor creations at the Dixon Gallery and Gardens April 9–13, 2013. The pieces, made completely or mostly out of cardboard, draw on the students' inspiration from the link between nature and culture.
The students displaying work are Nick Darmstaedter, Ric Evans, Alex Lee, Olivia Logan, Robbie McElhaney, Adra Maner, Melinda Parra, Jonathan Rodriguez, Nicole Trimble, Austin Williams, Lisa Williamson and Sean Winfrey.
"While all relating to the show's theme of nature and culture, individual works also touch on ideas of life and death, transformation, transience of time and objects, gender, beauty, history, competition, animal nature of humans, the relationship of the insect world with the human world, and music," explained Brown. "The exhibition will make a statement even as it disintegrates over time and with the elements."
The works will be displayed at the Dixon Gallery and Gardens throughout the grounds behind the museum. Artists have used a variety of both traditional sculpting/woodworking techniques such as laminating and carving, papermaking techniques, along with tabbing, bending and folding as well as non-traditional techniques such as knitting with cardboard "yarn."
This project was made possible by a generous gift of corrugated from International Paper.


text: Since 1996 Lynx has been crafting outdoor grills with the same premium quality and performance as commercial kitchens. The entry-level Sedona series offers the innovative features that Lynx is known for, including blue LED-lit knobs, halogen lights inside the grill, and the unique ProSear infrared burner with variable temperature control for everything from high-heat searing to low slow cooking. Made in the USA, Lynx grills boast seamless welded construction, so cleanup is fast and easy.