996,Copyright F1936 Celpress Neuron; Val: 529-539, March_ Expression of Constitutively Active CaMKII in Target Tissue Modifies Presynaptic Axon Arbor Growth Cat- Ca"" channels ligand-gated channels CTre @use Dong-Jing Zou and Hollis Cline Ilresult in autophosphory Irom Intracellular stores can Cold Spring Harbor Laboratory CaMKII (Hanson and Iation and prolonged activation Cold Spring Harbor, New York 11724 Schulman, 1992; Scott and Sodcrling; 1992; Schulman, intracellular Ca?' 1993). In this way, brief changes CaMkII relatively long-lasting incrcasas can leao Summary Goldring; activity (Millcr and Kennedy, 1986; Lisman ara 1988) . (Ca- Calcium/calmodulin-dependent protein kinase CaMKI has Leen snown j0 impontant several be regulated by synaptic activity could Mkii) Drosopnila; inhibition ot fors synaptic plast city: activity-dopendent contro therefore be involved activity by the induction Inhicitory peptide CaMkI nouronal growth: We tested whether increased Cam- modifies impairs learning Griffith et al ,1993,19941 postsynaptic optic tectal nourons can KII activity the neuromuscular juncticn synaptic transmission Xeno modify the development of rotinotecta axons (Wang 1994). CaMkII required tor iona-term presynaptic retinal pus. The elaboration of individua synaptic transmission the hippocam- potcntiation vivo belore and up to days axons was observed Malinow ct al  19891, pus (Malenka al , 1989; vaccinia - infecting the tectal cells with Lnrus Car uner CaMKII activity postsynaplic neurons Increased rying tha gene for constitutively active truncated Cam- 1994). synaptic (Peltit tranemissicn tCntialcs KII (tCaMKII}  Elevated postsynaptic CaMKII activity lacking u-CaMKII also dclicient in Knockout mice from developing the complexity prevented the arons some types of learnirg (Silva al , 15922, 1992b) and increasing arbors norma normai Plasticity Chapman 1995}. prosynaptic forms Some effects of tCaMKII on arbor branch retractions promote Fresynaptic CaMKII activity nburotans day after infection, but they morphology were Unas se8n 1990; ctal , 1991)- CaMKII mitterreleacclnetal became more dramatic by the third day: The results major constituent ot the postsynaptic density (Ken- suggest that postsynaptic CaMKI rolu in the plays al , 1983) and may inlluenco synaplic plasticity nedy presynaptic arbor structure development phosphorylating 3-nydroxy-S-methyl 4 -amino IAMPA} (McGlade" isoxazclepropionate [Ccepions cytoskeletal proteins (Jelter- Introduction al , 1992}, McCulloh by regulating nitric oxide and Schulman 1991}. circuits requires the coordinated The Iormation synthase acuvity (Nakane al , 1991). Davnl presynaptic postsynaptic Tne [ development CaMKIIin stnuctural plasticity Jxons cedn CaMKII activity correlato with peaks dendrites_Activity-dependent mechanisms thal operate High levels both antcrograde and retrograde directions JCi0ss growth and synaptogenosis severai neuron? ccntrolling the synapse aro likely tems, including tho visual system (Scholz et al , 1988; Umoonant studies growth and synaptogenesis (Coodman and Jensen etal,, 1991;Jlaotal,, 1932}. Same Vitto ncuronb Shatz; 1993; Jessell ana Kandel, 1933; Davis and Mur- Indicate that increased CaMKI activily Increases neurite such coordinaled control 19931 arid that decreased oulgrowth (Goshima phey; 1994). Evidence tor stong CaMMKII decreasas neurite growrth (Cabell and Audesirk, growth ad circuit formation in the neuranal 1593}. However, Jian et al. (1994) reparted that blocking changing  tectal Ahara visual  system frogs, N-methyi-D-aspartic acid (NMDA) receptor activity dis CaMKII has no effect on rolinal axon oulgrawth vitro. rupts tne topographic organization afferent inputs Manipulating kinase aclivity in vivo permits onc (Cline et al , 1987; Cline and Constanting-Paton; 1989; kinase activity the coordinatod the effect 5055 alters retinal axon morphologY the pre postsynaptc parlners. Scherer and Ucin; 19891 develanineni (Cline and Ccnstantine-Paton; 1990a) and presynaptic Drosophila, blocking kinase aclivity in vivo writh an inhib- grawth at the neuro 995]andchangesaxcnarbor neurona structure (Yen ctal,1993, pcptido increases 1994). The growth muscular Rourke 9941. However, the (Wang wunctan branch dynamics regulatcd vivo by the chronic signal transductlon pathways withn the postsynaptic retinal ons kinase inhibitors tadpoles (Cline and underlie such activity-dependcnt changes application nelrom -Paton , 199Cb}. In these Iast experiments Cne possibility is that in ncuronal structure are not clear. Cansiantinc growth; CaMKII activity probably intracellular Ca? following synaptic activity retina aron the rise activates tho multifunctional both - Postsynaptic neurons_= Ca-' Icalmodulin-ccpen- moditied pastsynaptic thatitis diflicult to define the rolc of pre - (CaMKII) in tectal cells. CaM- dent protein kinaso type development implicated in the controlof ncuronal growth retinal axons and kinase aclivity Kllhas bcen Targeted manipulation of kinase activity Soderling; 1992; tectal plasticity (Scott nemrons TCurona reveal Ihe possible role Post- tectal neurons could Schulran, 4931 cocrdinated control synaptic CaMKII aclivity activated by Ca? Icalmodulin bindlng CaMKII i This neuronal growth Tesul protein: domain regulatony Vaccinia has been we charctcnco Vecnar tat the enzyme incepon Knnus autophosphcrylation makas fcr use in cell culture (Moss, 1991}and has more ecenlly 993}. Increases Ca?- {calmodulin Ischuiman dent targeted populations votqe nicci neurons following aclivation ~gated Nsed Dcen intracellular Car"
529-539, March_ 996,Copyright F1936 Celpress Neuron; Val: Expression of Constitutively Active CaMKII in Target Tissue Modifies Presynaptic Axon Arbor Growth Ca"" channels ligand-gated channels CTre @use Cat- Irom Intracellular stores can Ilresult in autophosphory Iation and prolonged activation CaMKII (Hanson and Schulman, 1992; Scott and Sodcrling; 1992; Schulman, 1993). In this way, brief changes intracellular Ca?' can leao relatively long-lasting incrcasas CaMkII activity (Millcr and Kennedy, 1986; Lisman ara Goldring; 1988) . CaMKI has Leen snown j0 impontant several fors synaptic plast city: Drosopnila; inhibition ot CaMkI activity by the induction Inhicitory peptide impairs learning Griffith et al ,1993,19941 modifies synaptic transmission the neuromuscular juncticn (Wang 1994). CaMkII required tor iona-term potcntiation synaptic transmission the hippocam- pus (Malenka al , 1989; Malinow ct al  19891, Increased CaMKII activity postsynaplic neurons tCntialcs synaptic tranemissicn (Peltit 1994). Knockout mice lacking u-CaMKII also dclicient in some types of learnirg (Silva al , 15922, 1992b) and prosynaptic forms Plasticity Chapman 1995}. Fresynaptic CaMKII activity promote nburotans mitterreleacclnetal 1990; Unas ctal , 1991)- CaMKII major constituent ot the postsynaptic density (Ken- nedy al , 1983) and may inlluenco synaplic plasticity phosphorylating -amino 3-nydroxy-S-methyl 4 isoxazclepropionate IAMPA} [Ccepions (McGlade" McCulloh al , 1992}, cytoskeletal proteins (Jelter- and Schulman 1991}. by regulating nitric oxide synthase acuvity (Nakane al , 1991). Tne [ CaMKIIin stnuctural plasticity cedn High levels CaMKII activity correlato with peaks neuron? growth and synaptogenosis severai tems, including tho visual system (Scholz et al , 1988; Jensen etal,, 1991;Jlaotal,, 1932}. Same Vitto studies Indicate that increased CaMKI activily Increases neurite oulgrowth (Goshima 19931 arid that decreased CaMMKII decreasas neurite growrth (Cabell and Audesirk, 1593}. However, Jian et al. (1994) reparted that blocking CaMKII has no effect on rolinal axon oulgrawth vitro. Manipulating kinase aclivity in vivo permits onc 5055 the effect kinase activity the coordinatod develanineni the pre postsynaptc parlners. Drosophila, blocking kinase aclivity in vivo writh an inhib- pcptido increases neurona grawth at the neuro muscular wunctan (Wang 1994). The growth retinal ons regulatcd vivo by the chronic application kinase inhibitors tadpoles (Cline and Cansiantinc -Paton , 199Cb}. In these Iast experiments retina aron growth; CaMKII activity probably moditied both - Postsynaptic neurons_= thatitis diflicult to define the rolc of pre - pastsynaptic kinase aclivity development retinal axons and tectal nemrons Targeted manipulation of kinase activity tectal neurons could reveal Ihe possible role Post- synaptic CaMKII aclivity cocrdinated control neuronal growth Vaccinia Knnus has been we charctcnco Vecnar fcr use in cell culture (Moss, 1991}and has more ecenlly Dcen Nsed nicci targeted populations neurons Dong-Jing Zou and Hollis Cline Cold Spring Harbor Laboratory Cold Spring Harbor, New York 11724 Summary Calcium/calmodulin-dependent protein kinase (Ca- Mkii) be regulated by synaptic activity could therefore be involved activity-dopendent contro nouronal growth: We tested whether increased Cam- KII activity postsynaptic optic tectal nourons can modify the development of rotinotecta axons Xeno pus. The elaboration of individua presynaptic retinal axons was observed vivo belore and up to days uner infecting the tectal cells with vaccinia - Lnrus Car rying tha gene for constitutively active truncated Cam- KII (tCaMKII}  Elevated postsynaptic CaMKII activity prevented the arons from developing the complexity normai arbors increasing norma branch retractions Some effects of tCaMKII on arbor morphology were se8n day after infection, but they became more dramatic by the third day: The results suggest that postsynaptic CaMKI plays rolu in the development presynaptic arbor structure Introduction The Iormation Davnl circuits requires the coordinated development presynaptic Jxons postsynaptic dendrites_Activity-dependent mechanisms thal operate both antcrograde and retrograde directions JCi0ss the synapse aro likely Umoonant ccntrolling ncuronb growth and synaptogenesis (Coodman and Shatz; 1993; Jessell ana Kandel, 1933; Davis and Mur- phey; 1994). Evidence tor such coordinaled control neuranal growth ad circuit formation stong in the visual  system frogs, Ahara changing  tectal N-methyi-D-aspartic acid (NMDA) receptor activity dis rupts tne topographic organization afferent inputs (Cline et al , 1987; Cline and Constanting-Paton; 1989; Scherer and Ucin; 19891 alters retinal axon morphologY (Cline and Ccnstantine-Paton; 1990a) and presynaptic structure (Yen ctal,1993, 995]andchangesaxcnarbor branch dynamics Rourke 9941. However, the signal transductlon pathways withn the postsynaptic nelrom underlie such activity-dependcnt changes in ncuronal structure are not clear. Cne possibility is that the rise intracellular Ca? following synaptic activity activates tho multifunctional Ca-' Icalmodulin-ccpen- dent protein kinaso type (CaMKII) in tectal cells. CaM- Kllhas bcen implicated in the controlof ncuronal growth TCurona plasticity (Scott Soderling; 1992; Schulran, 4931 CaMKII i activated by Ca? Icalmodulin bindlng regulatony domain protein: This Tesul autophosphcrylation tat makas the enzyme incepon dent Ca?- {calmodulin Ischuiman 993}. Increases intracellular Car" following aclivation votqe ~gated