The Role of Dopaminergic and Cholinergic Neurons in the Substantia Nigra Pars Compacta and Nucleus Basalis in Working Memory

Abstract

Working memory is the basis of fundamental learning and cognition, as it involves the updating, maintenance, and manipulation of novel information to direct subsequent behavior. This executive function has been linked to the cholinergic and dopaminergic systems through pharmacological interventions, but effective mediation of working memory disorders, such as Alzheimer’s and Parkinson’s disease, has been unsuccessful. Previous research limitations include confounding results due to disruption of other neurotransmitter systems, irreversible structural damage to the brain, and slow-acting pharmacological interventions that cannot match the fast temporal dynamics of acetylcholine and dopamine. The use of optogenetics in conjunction with genetically-restricted recombinase-driver rats circumvents many of these limitations to allow for greater understanding of these neurotransmitters in terms of temporal dynamics and processing of working memory, in addition to detangling the complex network of cholinergic and dopaminergic pathways in cognitive function. To investigate the role of these two neurotransmitter systems in working memory, cholinergic and dopaminergic neurons in the NB and SNc, respectively, were selectively inhibited to observe for changes in behavioral responses during performance of a working memory task. A significant decrease in performance accuracy occurred when dopaminergic neurons in the SNc were inhibited, but no change in accuracy was detected when cholinergic neurons in the NB were selectively inhibited. Based on these results, it is evident that dopaminergic neurons in the SNc play a significant role in working memory, whereas the role of NB cholinergic neurons may have a secondary or non-causal role in working memory, warranting further investigation.