MemoryRecAll · Two-photon all-optical interrogation of auditory cortex circuit supporting working memory representations

Working memory refers to the brain capacity for encoding sensory stimuli and maintaining information suspended for imminent processing, over a short timespan (few seconds). This ability is crucial for numerous simple and intricate tasks in humans and animals (keeping in mind a sequence, learning, speech…). Despite its importance, the mechanisms underlying this process remain largely unknown. Different theoretical models have been proposed to recapitulate working memory. Among them, attractor dynamics within recurrent networks facilitate self-sustained activity that holds information as a form of memory. Working memory, since its first descriptions, has been pinpointed to higher-order associative frontal and prefrontal regions of the brain. However, growing evidences suggest widespread representations, spanning also sensory cortices. A recent research causally demonstrated the necessity of the primary auditory cortex to perform an auditory-based working memory task. The main objective of the proposed project is to reveal the existence of working memory representations in auditory cortex and to analyze the circuit supporting them, employing the concept of attractor dynamics. This goal will be achieved by combining ultrafast acousto-optic two-photon (2P) calcium and voltage imaging, precise optogenetics and animal behavior. This approach will provide information regarding the spatial organization and identity of neurons responding during the retention phase of the task and enables the subsequent manipulation of such neurons with unprecedented spatiotemporal accuracy. Perturbation experiments will test the predictions of attractor dynamics theory in relation to working memory representation and probe synaptic connectivity within functionally identified neurons. In conclusion, I will combine cutting-edge optical approaches with analytical methods to causally dissect the network underlying working memory representations in auditory cortex.