Chapter 10 Chemical signalling and striatal interneurones

Publisher Summary The majority of neostriatal neurones are mediumsized spiny neurones, which have diameters between 10 and 20 pm. These cells were originally believed to be interneurones; however, retrograde transport studies established them as projection neurones. Parallel studies showed that GABA inhibition (or more strictly disinhibition) controls the majority of the functional activity in the basal ganglia. In addition to the medium-sized spiny cells, the larger aspiny cells, 20–60 pm diameters, constitute some 4%– 5 % of all striatal neurones, and these are now known to be short axoned interneurones, although there are occasional reports of aspiny projection neurones. These interneurones integrate activity between output pathways through the striatum providing feed forward and feedback loops. In addition, interneurones may represent relatively specific targets for cortical or thalamic inputs. This chapter discusses some of the recent work exploring the phenotypes of striatal interneurones and present evidence indicating that nitric oxide may be a novel intercellular messenger in the striatum modulating the effects of glutamate on N-methyl-D-aspartate (NMDA) receptors expressed by striatal neurones. Stimulation of NMDA receptors in vivo activates local acetylcholine (ACh) release as does local application of substance P and substance P agonists. The exquisite sensitivity of cholinergic neurones to substance P and NMDA suggests that these neurones represent an important target both for local striatal axon collaterals containing substance P, and thalamic excitatory inputs releasing glutamate.