Consolidating transient sensory experiences into long-lasting memories is a fundamental function of the brain, linked to synaptic plasticity. The importance of sleep for promoting this process, and the disruptive effect of sleep deprivation on it, have been appreciated for nearly a century. However, it remains unclear how sleep-associated changes in the activity of specific brain circuits contribute to sensory plasticity. Using a combination of longitudinal recordings of neuronal activity in freely-behaving mice, recently-developed optogenetic strategies, novel computational tools for characterizing network activity patterns, we will test the necessity and sufficiency of sleep-associated patterns of thalamocortical activity in consolidating a simple form of experience dependent plasticity. We will test the hypothesis that coherent firing during network oscillations unique NREM sleep plays a causal role in promoting plasticity between the thalamic lateral geniculate nucleus (LGN) and the primary visual cortex (V1) following presentation of a novel visual stimulus. Here we will selectively manipulate cortical, thalamocortical and corticothalamic neuronal populations in a state specific manner. We will measure both response changes in individual V1 and LGN neurons to the presented stimulus, and behavioral responses to the presented stimulus in the context of a visual discrimination task. We will test whether neurons that are selectively responsive to the visual stimulus play a critical role in guiding network activity patterns during subsequent sleep, acting as an instructive mechanism for circuit plasticity. Finally, we will test whether following visual experience, sleep-dependent communication between V1 and the perirhinal cortex (essential for visual recognition memory) is responsible sleep-dependent discrimination learning.
The proposed studies will provide new insights into how sleep uniquely contributes to long-term memory formation. This work has the potential to lead to targeted interventions for cognitive dysfunction induced by sleep loss, and interventions for psychiatric disorders where both sleep and cognition are adversely affected, including schizophrenia, depression, autism, and dementia.
|Clawson, Brittany C; Durkin, Jaclyn; Suresh, Aneesha K et al. (2018) Sleep Promotes, and Sleep Loss Inhibits, Selective Changes in Firing Rate, Response Properties and Functional Connectivity of Primary Visual Cortex Neurons. Front Syst Neurosci 12:40|