The mammalian neocortex underlies many perceptual, cognitive and affective functions. It also has a layered structure with conserved circuit elements and connectivity but how this structure leads to function remains a mystery. We will use silicon probes spanning cortical layers combined with optogenetic tagging and manipulation to gather high-resolution data about cell-cell communication in the cortex during varying brain states. Gathering fundamental information about cortical neuronal cell types, layers and how they transmit information will lead to a fuller picture of how the cortex operates and accomplishes its remarkable achievements.
Cortical and hippocampal networks during sleep and wake
Sleep is thought to have homeostatic functions for our brains and has also been shown to mediate memory consolidation. Evidence for homeostatic function of sleep is that without sleep our brains malfunction: we remember poorly, our cognition becomes faulty, psychosis can emerge and epileptic patients can have seizures. On the other hand during wake we accumulate experience and learn new information and decades of research has shown that memory is actually improved after sleep.
How does sleep both bring cells/synapses back to the status quo for homeostatic reasons and yet also reinforce new changes to become strengthened. We aim to study which cells and connections are maintained and which are pulled back to previous states after learning behaviors using a combination of high density electrophysiologic recordings, sleep and learning paradigms and optogenetics.
Depression-related stress circuits and antidepressant action
Major depressive disorder affects millions of people worldwide every year and yet we do not understand its basic neurobiology. We do know that it is triggered frequently by stress and in fact stress paradigms in rodents mimic many depression symptoms in patient populations - including disturbances of sleep, appetite, daily activity, motivation and normal enjoyment. We are undertaking novel methods to evaluate how these behaviors may be underlain by brain circuit changes.
We compliment the approach of understanding these stress circuits with an approach targeting the capacity of antidepressants to reverse or address these changes - including a specific focus on ketamine, an exciting rapid-acting antidepressant that appears to operate via novel mechanisms of action in the brain.