Striatum inputs

D2 Mostly in striatum, nucleus accumbens and olfactory tubercle but also on neuron cell bodies in substantia nigra and ventral tegmentum where they are the autoreceptors for locally (dendritic) released DA. The loss of specific D2 antagonist binding in the striatum after lesions of the afferent nigro-striatal tract indicates their presynaptic autoreceptor role on terminals there. Other lesion studies have also established D2 receptors on other inputs such as the cortico striatal tract. 

The ability of the striatum to apparently function normally until it has lost much of its DA can be ascribed in part to denervation supersensitivity, the degeneration of the DA input resulting in an increase in postsynaptic DA receptors and partly to the remaining neurons producing more DA. This is supported by measurements in humans which show that the HVA DA ratio, a measure of DA turnover, is much greater in Parkinsonism patients and by microdialysis in rats with 6-OHDA lesions of the nigrostriatal tract, when the reduction in perfusate (released) DA is very much less than that of neuronal (stored) DA. 

Figure 15.2(b) A schematic presentation of possible basal ganglia circuitry in Parkinson s disease. In PD there is little or no inhibitory nigrostriatal input to the striatum so the Ind Path is active and GPext is inhibited. This will then have less depressant effect on the SThN which will be free to drive the GPint (and SNr) and so reduce cortico-thalamic traffic and produce akinesia. See text for detail. Pathway activity — low — normal — high... 

Two features require some comment. The induction of depolarisation block in DA neurons needs afferent input to the nuclei, since prior lesion of the striatum and nucleus... 

Due to its relevance to an understanding of movement disorders, the motor circuit has received the most attention. This circuit is centered on somatosensory, motor and premotor cortices, which send projections to the motor portions of striatum. The connections between the striatum and the basal ganglia output nuclei (GPi/SNr) are organized into direct and indirect pathways [1]. The direct pathway is a monosynaptic projection between striatum and GPi/ SNr, while the indirect pathway is a polysynaptic connection that involves intercalated neurons in GPe and STN. Some striatofugal neurons may also collateralize more extensively, reaching GPe, GPi/SNr and STN. Other motor -related inputs to striatum and STN arise from the intralaminar thalamic nuclei, i.e. the centromedian and parafascicular nuclei (CM/Pf). 

A global view of consciousness is that it is generated throughout the entire brain, as a result of synchronisation of relevant neural networks. Specific systems or regions—for example the cerebral cortex, brainstem reticular formation and thalamic nuclei—may be key anatomical integrators. Areas with the most widespread interconnections are pivotal, and on this basis the cortex and thalamus are more relevant than cerebellum and striatum for example. Frontal cortex for example connects with every other brain region, both in terms of input and output, with 80% of such connections accounted for by cortico-cortical connections. Thalamic intralaminar nuclei are, in conjunction with the reticular nucleus, reciprocally connected to all cortical areas. By contrast the cerebellum has very few output pathways and striatal-cortical input is (via the thalamus) confined to frontal lobe. 

The ventral striatum, like its dorsal counterpart, is part of a system of CSTC loops. Only recently has it become clear that these loops are as segregated and discrete as those in the dorsal striatum. Glutamatergic inputs, which arise from the orbital and medial prefrontal cor-... 

Inputs from ascending dopamine pathways originating in the substania nigra, pars compacta, play a crucial role in coordinating the output from the striatum (Aosaki et ah, 1994). Explicit dopamine hypotheses for Tourette s syndrome posit either an excess of dopamine or an increased sensitivity of D2 dopamine re-... 

Rominger A, Forster S, Zentner J et al (2002) Comparison of the ORL1 receptor-mediated inhibition of noradrenaline release in human and rat neocortical slices. Br J Pharmacol 135 800-6 Sandor NT, Kiss J, Sdndor A et al (1991) Naloxone enhances the release of acetylcholine from cholinergic intemeurons of the striatum if the dopaminergic input is impaired. Brain Res... 

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