Cholinergic system striatum

This laboratory, as well as others, has shown unequivocally that PCP affects a variety of parameters related to neurotransmission in several neuronal systems. This paper has focused on evidence for the involvement of dopaminergic, cholinergic, and glutama-tergic pathways, and evidence of their interactions in the rat striatum. However, the effects of PCP undoubtedly involve other neuronal systems in other brain areas. Thus, it must be borne in mind that the data discussed in this paper cannot possibly account for the more complex behavioral effects of PCP. 

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. 

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). 

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. 

Northern blots and in situ hybridization data showed that BDNF mRNA is mainly present in the brain and suggested a putative trophic effect for neurotrophins not only on PNS neurons but also on intrinsic neurons of the central nervous system (CNS). In fact, both NGF and BDNF were found to support central cholinergic neurons in culture (Martinez et al., 1985 Hefti, 1986 Hartikka and Hefti, 1988 Hatanaka et al., 1988 Alderson et al., 1990 Knusel et al., 1991). However, only BDNF supported chick and rat retinal ganglion cells, dopaminergic neurons of the ventral mesencephalon, and GABAergic neurons of the basal forebrain and striatum (Lindsay et al., 1985 Alderson et al., 1990 Hyman et al., 1991, 1994 Knusel et al., 1991, 1994 Ventimiglia et al., 1995). 

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