Cell types Types of cells in the striatum include: Medium spiny neurons (MSNs), which are the principal neurons of the striatum. They are GABAergic and, thus, are classified as inhibitory neurons. Medium spiny projection neurons comprise 95% of the total neuronal population of the human striatum. Medium spiny neurons have two characteristic types: D1-type MSNs and D2-type MSNs. A subpopulation of MSNs contain both D1-type and D2-type receptors, with approximately 40% of striatal MSNs expressing both DRD1 and DRD2 mRNA. Cholinergic interneurons release acetylcholine, which has a variety of important effects in the striatum. In humans, other primates, and rodents, these interneurons respond to salient environmental stimuli with stereotyped responses that are temporally aligned with the responses of dopaminergic neurons of the substantia nigra. The large aspiny cholinergic interneurons themselves are affected by dopamine through D5 dopamine receptors. Dopamine also directly controls communication between cholinergic interneurons. There are many types of GABAergic interneurons. The best known are parvalbumin expressing interneurons, also known as fast-spiking interneurons, which participate in powerful feedforward inhibition of principal neurons. Also, there are GABAergic interneurons that express tyrosine hydroxylase, somatostatin, nitric oxide synthase and neuropeptide-y. Recently, two types of neuropeptide-y expressing GABAergic interneurons have been described in detail, one of which translates synchronous activity of cholinergic interneurons into inhibition of principal neurons. These neurons of the striatum are not distributed evenly. There are two regions of neurogenesis in the brain – the subventricular zone in the lateral ventricles, and the dentate gyrus in the hippocampal formation. Neuroblasts that form in the lateral ventricle adjacent to the striatum, integrate in the striatum. This has been noted in the human striatum following an ischemic stroke. Injury caused to the striatum stimulates the migration of neuroblasts from the subventricular zone, to the striatum, where they differentiate into adult neurons. The normal passage of SVZ neuroblasts is to the olfactory bulb but this traffic is diverted to the striatum after an ischemic stroke. However, few of the new developed neurons survive. Inputs The largest connection is from the cortex, in terms of cell axons. Many parts of the neocortex innervate the dorsal striatum. The cortical pyramidal neurons projecting to the striatum are located in layers II-VI, with the most dense projections come from layer V. They end mainly on the dendritic spines of the spiny neurons. They are glutamatergic, exciting striatal neurons. The striatum is seen as having its own