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Content archived on 2024-06-18

The influence of neuromodulators on medial prefrontal cortical microcircuits during working memory

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The mechanism of working memory

Dissecting how our brain processes new and stored information – also known as working memory – is necessary for understanding the determinants of learning skills and attention.

Our capacity to maintain and manipulate task-relevant information is governed by our working memory. The part of our brain responsible for memory function is the medial prefrontal cortex (mPFC). Although the neuronal processes necessary for working memory tasks have been elucidated, we lack a mechanistic explanation for this cortical activity, and precisely how neuromodulators such as dopamine can influence it. Scientists on the EU-funded PFC-DOPA (The influence of neuromodulators on medial prefrontal cortical microcircuits during working memory) project set out to shed light on this phenomenon. For this purpose, the first step was to characterise the dynamics of mPFC activation and determine how neuromodulators affect these representations. In this context, they combined in vivo electrophysiological techniques and optogenetic manipulations to directly assess the role of dopamine on neocortical activity and working memory. Researchers labelled the dopamine neurons and were able to define the anatomical connectivity between the dopamine neurons and the PFC as well as obtain information on dopamine-related responses. They discovered a heterogeneity in dopamine axons among different regions of the PFC, suggesting differences in dopamine responses. The in vivo work indicated that dopamine might play a role in modulating the incoming input from the hippocampus to the PFC during behavioural tasks. This dopaminergic effect was mediated by the D1 receptor and the firing patterns observed correlated to tasks related to attention and working memory. Overall, the findings of the PFC-DOPA study provide fundamental insight into the neuronal mechanism underlying working memory. Long term, this information will help comprehend the molecular basis of attention problems and learning difficulties in children.

Keywords

Working memory, learning, medial prefrontal cortex, dopamine, D1 receptor