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Investigation into the chemical sensitivities of single nerve cells in the caudate nucleus in relation to associated structures of the brain York, Donald Harold

Abstract

Considerable evidence has been accumulated suggesting the possible neurotransmitter functions of acetylcholine (Ach) and dopamine in the central nervous system. In particular the caudate nucleus is believed to contain cholinergic and dopaminergic cells, as well as the specific enzymes responsible for the synthesis and destruction of these chemical entities. In this study, the technique of microelectrophoresis has been applied to cells of the caudate nucleus in order to investigate the particular location and pharmacological properties of caudate neurones in relation to some other structures of the brain. Neurones located between the surface and 4.5 mm deep in the head of the caudate nucleus of cats have been tested for their acetylcholine and dopamine sensitivity. Of 427 cells examined, about 10% were excited by acetycholine, and a further 10% depressed, while the remaining majority of the cells were unaffected. The cells which were excited lay at an average depth of 860μ below the surface (5% confidence limits ±l65μ), while those depressed were situated at 2170μ (5% confidence limits ±350μ). Both excitatory and depressant responses could also be elicited by electrical stimulation of the nucleus ventralis anterior thalami (VA). The responses appeared to be "muscarinic" in character, since they were abolished by atropine and were elicited by acetyl-β-methylcholine as effectively as by acetylcholine itself. Of 152 cells examined, about 7% were excited by dopamine, and 64% depressed, while the remaining majority of cells were unaffected. The characteristic depth stratum for excitatory and depressant responses of cholinergic cells was not found for dopaminergic cells. Electrical stimulation of the substantia nigra (SN) elicited an evoked response from caudate neurones which was depressed by dopamine. It was found that a dopamine induced depression could be blocked by dibenzyline, but not by dichloroisopropylnoradrenaline (DCI). This would suggest that the dopamine sensitive cells have ∝-adrenergic receptors. Electrical stimulation of the nucleus centromedianus thalami (CM) caused depression of single cell activity in the caudate, coinciding with depression caused by iontophoretically applied dopamine. Taken with the earlier observation that the release of Ach from the caudate can be enhanced by VA stimulation, it has been concluded that the present results indicate a final cholinergic link in the pathway from VA to the caudate nucleus. Furthermore, the demonstration of enhanced dopamine output from the caudate upon CM stimulation, with reference to present results, indicates an inhibitory dopaminergic link in this thalamo-caudate pathway. A nigrostriatal tract causing excitatory responses at the caudate termination has been observed. However, the effective blockage of the excitatory SN evoked response by iontophoretic application of dopamine would suggest a possible dominance of a thalamic inhibitory neural mechanism over the excitatory input from SN operated via a dopaminergic link.

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