‘What we think we become’.
We study how brains store experiences as memories, and how the expression of knowledge activates information that is relevant without activating what is irrelevant. Our laboratory uses molecular, electrophysiological, behavioral, engineering, and theoretical methods to investigate these fundamental and interrelated issues in neuroscience.
In work with Todd Sacktor's laboratory, we identified protein kinase M zeta (PKMzeta) as a key molecular component of long term memory. PKMzeta is a persistently active kinase that maintains enhanced electrical communication at synapses between neurons. We discovered PKMzeta's role in long-term memory storage by erasing long-term memory for a particular place busing PKMzeta inhibitors in hippocampus a day, and even a month after rats learned a place avoidance task. Importantly, PKMzeta inhibition or destruction does not alter baseline synaptic activity nor does it impair the ability to relearn and remember the same information during retraining after the erasure. Subsequent work has shown that PKMzeta is involved in memory storage in many parts of the brain. Our initial work on PKMzeta and memory was selected as one of the ten "Breakthroughs of the Year 2006" by the editors of Science, and received substantial attention in the popular media, including the New York Times. We are continuing to study PKMzeta's role in the synaptic organization of memory and in maintaining and organizing memory-related brain circuits and the activity that expresses memory and experience.
We are investigating the role of the hippocampus in controlling how we choose relevant information to process, by studying the interaction of memories and neural activity in signaling information from multiple spatial frames. While rats and mice solve problems that require using relevant information and ignoring distractions, we make recordings from multiple sites and use computational tools to decode information from these recordings about cognitive variables like current location, memory, attention, and cognitive control. Our findings demonstrate that neural activity is exquisitely coordinated on multiple time scales from milliseconds to minutes, so that neurons that represent the same information discharge together in time, but are desynchronized when representing conflicting information. We are studying specific disturbances of this neural coordination in rat and mouse models of schizophrenia, intellectual disability, autism, depression, and epilepsy, and other models of dysfunction.
We developed an inexpensive, miniature, wireless digital device for recording electrical brain activity from rats that have abnormalities of neural coordination to learn whether this activity underlies cognitive impairments, and whether behavioral and pharmacological interventions can attenuate the neural and cognitive abnormalities. Together with business and engineering partners, we founded Bio-Signal Group Corp. and have developed our brain-recording technology for medical applications in both conventional and novel clinical settings. We have also founded Med2.0 to develop and commercial intellectual property in information technology tools for improved care coordination in mental health.