Dopaminergic A10 neurones are involved in cognitive functions

It is demonstrated here that selective lesions of dopaminergic A10 neurones in the rat produce a severe and specific impairment in retention of delayed alternation.

Abstract

Delayed response tasks are widely considered to be particularly sensitive in demonstrating cognitive deficits after lesions of the prefrontal cortex in all species of mammals1. In rodents, these deficits are usually tested in a T-maze and are more pronounced after lesion of the anterior part of the striatum than after prefrontal cortex ablation2. In effect, the striatum is capable of assuming cortical functions either when the prefrontal cortex is poorly developed as in the lower mammals3 or immature as in the early life of primates4. The prefrontal cortex and anterior striatum—the so-called prefrontal system5—are functionally and anatomically related. The prefrontal area specifically involved in delayed alternation6 receives projections from the mediodorsal thalamic nucleus (MD)7 and sends axons to the anterior striatum as well as to the MD3,7. Recently, a detailed anatomical study of the connections of the prefrontal system revealed the existence of important projections from the mesencephalic dopaminergic A10 neurones and the mediodorsal nucleus that converge on the prefrontal cortex8. Axons of the A10 system also project to the anterior part of the striatum9,10. The influence of dopaminergic A10 neurones on frontal lobe functions remains obscure, but some observations concerning the behavioural, pharmacological and biochemical effects of neuroleptics and psychostimulants have supported the idea that these dopaminergic neurones could have a role in the pathogenesis of schizophrenia 11–13. Furthermore, the major symptoms observed in schizophrenic patients such as cognitive and attention disturbances have been attributed to a dysfunction of both prefrontal cortex and striatum14–16. Thus, in addition to their anatomical connections, the dopaminergic A10 neurones may be functionally related to the prefrontal cortex and striatum. These data encouraged us to investigate whether A10 neurones are functionally related to the prefrontal system and in particular if they are involved in cognitive processes measured in a delayed alternation task. We demonstrate here that selective lesions of dopaminergic A10 neurones in the rat produce a severe and specific impairment in retention of delayed alternation. On anatomical and behavioural grounds the dopaminergic A10 system could therefore be considered as a rather better indicator of frontal system function than the mediodorsal thalamic nucleus.