PFC-DOPA · The influence of neuromodulators on medial prefrontal cortical microcircuits during working memory

Working memory (WM) is the capacity to temporarily maintain and manipulate task-relevant information, and has long been thought to crucially depend upon medial prefrontal cortex (mPFC) function. Investigations employing many different approaches have identified neuronal processes strongly linked with, and necessary for, working memory tasks. Prominently, a persistent increase in firing rate during the interval between cue presentation and action has been observed. Furthermore, these processes can be modified by levels of neuromodulators such as dopamine (DA), in keeping with the proposed role of this neurotransmitter in modulating working memory function. However a mechanistic explanation for this cortical activity, and precisely how neuromodulators can influence it, remains lacking. The aim of this project is to 1) characterise the dynamics of patterns of mPFC activation at the level of neural populations and, 2) determine how the neuromodulator DA influences these representations. To do this, I will combine advanced in vivo electrophysiological techniques (high density multi-site population recordings and whole-cell patch clamp) with optogenetic manipulations to directly assess the role of DA on patterns of neocortical activity and WM. This work will shed light on the mechanisms that underlie short term memory storage within the nexcortex, and the influences that attention and reward can exert on these mechanisms.""