Striatum interneurons

Cerebral cortex (layer I-VI, selected interneurons and principal cells) hippocampus (selected interneurons and principal cells) pallidum striatum (interneurons) thalamic relay nuclei olfactory bulb (mitral cells and interneurons) cerebellum (Purkinje cells and granule cells) deep cerebellar nuclei amygdala basal forebrain substantia nigra pars reticulata inferior colliculus brainstem... 

Berlanga, M.L., Olsen, C.M., Chen, V. et al. Cholinergic interneurons of the nucleus accumbens and dorsal striatum are activated by the self-administration of cocaine. Neuroscience. 120 1149, 2003. 

NGF also has actions within the CNS, although it is not particularly abundant in the CNS. Its synthesis appears to be largely restricted to the hippocampus and neocortex, and even in these regions it is present at relatively low concentrations relative to the other neurotrophins. The most prominent population of NGF-responsive neurons expressing TrkA are the basal forebrain cholinergic neurons. The principal projections of these neurons are to the hippocampus and cortex, which conforms with the concept that NGF acts as a target-derived trophic factor in the CNS, just as it does in the peripheral nervous system (PNS). NGF also acts on a subpopulation of cholinergic neurons within the striatum. These interneurons express the NGF receptor, TrkA, and respond to NGF. However, they do not appear to rely entirely on NGF for their survival, and the specific actions of NGF on this neuronal population have not been clearly defined. NGF may also have autocrine actions in the CNS, as some neuronal populations have been identified that express both TrkA and NGF. 

GABA is the predominant intrinsic transmitter of the basal ganglia. Inhibition and disinhibition are considered to be the most important modes of information transfer in the basal ganglia. Ninety-five percent of all neurons in the striatum are GABAergic medium spiny neurons. These neurons are the striatal output neurons. The medium spiny neurons which give rise to the direct pathway also contain substance P or dynorphin as a co-transmitter, while those striatal output neurons that give rise to the indirect pathway contain enkephalin as a co-transmitter. Most striatal interneurons, as well as neurons in GPe, GPi and SNr are also GABAergic. Because striatal and GPe... 

Acetylcholine. Most of the acetylcholine in the basal ganglia is found in the striatum, as the neurotransmitter of the large spiny interneurons, which account for about 3% of all striatal neurons. Both muscarinic and nicotinic cholinergic receptors are found in the striatum. Postsynaptic muscarinic receptors may inhibit transmitter release from... 

Dopamine acts on G-protein-coupled receptors belonging to the D1 -family of receptors (so-called D1-like receptors , or DlLRs, comprised of Dl- and D5-receptors), and the D2-family of receptors ( D2-like receptors , or D2LRs comprised of D2-, D3- and D4-receptors). Dl LRs stimulate adenylate cyclase activity and, possibly, also phosphoinosit-ide hydrolysis, while D2LRs reduce adenylate cyclase activity. In the striatum, DlLRs are predominately associated with medium spiny neurons of the direct pathway, while D2LRs have been found as autoreceptors on dopaminergic terminals, as heteroreceptors on cholinergic interneurons, and on indirect pathway neurons. In the SNr, DlLRs are located on terminals of the direct pathway projection, while D2LRs appear to function as autoreceptors. 

Somatostatin inhibits secretion of growth hormone and other hormones such as prolactin from the anterior pituitary and is widely distributed in the brain in interneurons and projection pathways. All parts of the cortex contain local circuit somatostatin positive neurons, concentrated in layers V and VI, as does the amygdala and striatum. The nucleus accumbens and adjacent ventral putamen and caudate—designated limbic striatum—have particularly high concentrations of fibres. By contrast, TRH which regulates release of thyroid stimulating hormone and prolactin by the pituitary is generally confined to nuclei in and around the hypothalamus. 

Dopamine is a catecholamine (see Chapter 10 and Fig. 31.2) whose actions are mediated by dopamine receptors that are classified as Dj-like (Dj, D5) or D2-like (D2, D3, D4). Dopamine actions on Dj receptors exert an excitatory effect, whereas the actions of dopamine on D2 receptors inhibit neuronal activity. The loss of striatal dopamine produces an imbalance in information processing in the neostriatum that modifies transmission in other basal ganglia regions. Also important in neural transmission are the striatal interneurons that are found within the confines of the striatum, that use the excitatory neurotransmitter acetylcholine, and that modulate the activity of striatal output neurons. 

The efficacy of anticholinergic drugs in parkinsonism is likely due to the ability to block muscarinic receptors in the striatum. In the absence of the inhibitory action of dopamine, the actions of the intrastriatal cholinergic interneurons are unopposed, yielding enhanced stimulation of muscarinic receptors. Blockade of these receptors reduces striatal activity. The muscarinic antagonists exert only modest antiparkinsonian actions and thus are most commonly used during the early stages of the disease or as an adjunct to levodopa therapy. 

The brain stem cholinergic neurons are essential for the regulation of sleep-wake cycles via projections to the thalamus. The cholinergic interneurons in the striatum modulate striatal GABAergic neurons by opposing the effects of dopamine. Increased cholinergic tone in Parkinson s disease and decreased cholinergic tone in patients treated with neuroleptics are examples of an imbalance of these two systems in the striatum (Cala-bresi et al., 2000). 

Neuropeptide Y [NPY] is a 36-amino acid peptide. The function of NPY, one of the most abundant peptide transmitters of the mammalian brain, remains unclear because of a lack of specific receptor antagonists. NPY meets many of the criteria of a neurotransmitter itself. NPY is costored and interacts with several monoaminergic neurons within the CNS [Lundberg et al. 1982], for example, noradrenergic afferents from the nucleus solitary tract to the amygdala. Both somatostatin and NPY colocalize at GABA interneurons within the amygdala, neocortex, and striatum. NPY also selectively modulates N-methyl-D-aspartate-induced hippocampal activation (pyramidal neurons] via oreceptors [Debonnel et al. 1994]. 

Landwehrmeyer GB, Standaert DG, Testa CM, Penney JB, Jr., Young AB (1995) NMDA receptor subunit mRNA expression by projection neurons and interneurons in rat striatum. J Neurosci 15 5297-5307. 

Dayer AG, Cleaver KM, Abouantoun T, Cameron HA (2005) GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. J Cell Biol 168 415-427... 

Kreitzer AC, Malenka RC (2005) Dopamine modulation of state-dependent endocannabinoid release and long-term depression in the striatum. J Neurosci 25(45) 10537—45 Kreitzer AC, Regehr WG (2001) Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto purkinje cells. Neuron 29 717-27 Kreitzer AC, Carter AG, Regehr WG (2002) Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. Neuron 34 787-96... 

Both cholinergic interneurons and cholinergic projection neurons can be found in the CNS. Cholinergic intemeurons are mainly located in the striatum and nucleus accumbens. Most cholinergic projection neurons originate from the basal forebrain (projections to the cerebral cortex and hippocampus) and the brainstem (projections to mid-brain and brainstem) (Mesulam, 2004 Smythies, 2005). 

The interactions between the muscarinic acetylcholine system and the dopaminergic system are bidirectional and dopamine also has a modulatory effect on the release of acetylcholine (Di Chiara et al., 1994). Dopamine D2 receptors (Alcantara et al., 2003) and dopamine D5 receptors (Berlanga et al., 2005) are localized on cholinergic neurons and interneurons in the striatum, nucleus accumbens, forebrain, and diencephalon. 

Alcantara AA, Chen V, Herring BE, Mendenhall JM, Berlanga ML. 2003. Localization of dopamine D2 receptors on cholinergic interneurons of the dorsal striatum and nucleus accumbens of the rat. Brain Res 986 22-29. 

Reduced density of cholinergic interneurons in the ventral striatum in schizophrenia An in situ hybridization study. Biol Psychiatry 58 408-416. 

Holt DJ, Herman MM, Hyde TM, Kleinman JE, Sinton CM, et al. 1999. Evidence for a deficit in cholinergic interneurons in the striatum in schizophrenia. Neuroscience 94 21-31. 

---