Cholinergic stimulation of the substantia negra

Abstract

Convergent lines of research suggest there exists an excitatory cholinergic input to the substantia nigra from the pedunculopontine tegmental nucleus and possibly the laterodorsal tegmental nucleus. Previous work has suggested that microinjection of cholinergic agonists into substantia nigra elicits behaviours performed with a high frequency but with a low current rate (Winn 1991). Experiments carried out during my PhD have demonstrated that: Microinjection of cholinergic agonists to anterior substantia nigra (SN) elicited increased consumption of palatable food such as spaghetti but not rat maintenance diet in pre-satiated rats. Stimulation of behaviour was achieved using direct agonists for either muscarinic or nicotinic cholinergic receptors (carbachol and nicotine respectively). Stimulation of behaviour was also achieved using the indirect cholinergic agonist neostigmine which blocks the de-activation of endogenous acetylcholine by AChE. Increased feeding elicited by cholinergic stimulation of the anterior SN was abolished by a selective lesion of ascending dopamine (DA) neurones which significantly depleted caudate DA levels but left accumbens DA levels unaltered. A behaviourally potent dose of carbachol caused a significant increase in the response to different doses of nicotine suggesting an additive effect of muscarinic and nicotinic stimulation at the doses used. Administration of cholinergic agonists to the VTA or SN caused indistinguishable effects on responding for conditioned reinforcement. Cholinergic stimulation caused increased responding for a conditioned reinforcer and also reinstated responding at the primary reward source. The functional significance of the cholinergic innervation of the DA- containing neurones of the substantia nigra is discussed with reference to its relationship to the neighbouring ventral tegmental area, and their innervation of the caudate-putamen and the nucleus accumbens. Cholinergic neurones in the PPTg and LDTN appear to exert a tonic control over the activity of midbrain DA-containing neurones. It is suggested that cholinergic control of midbrain DA-containing neurones facilitates the processing of information in the striatum and hence influence the selection of an appropriate behavioural response to a given situation.