Epigenetic and transcriptional mechanisms that maintain neuronal identity:
Most neurons in the mammalian brain have a lifespan that roughly matches that of the animal. We are interested in how forebrain neurons maintain their transcriptional identity to allow stable circuit function. Using RNAseq and ATACseq from sorted neurons, we have mapped cell type-specific patterns of transcription and genome accessibility with high precision. Using computational and experimental approaches, we are trying to identify the networks of transcription factors and cis regulatory regions that permit cells to maintain appropriate expression of neuronal effectors like ion channels and receptors.
The dark side of homeostatic plasticity:
Together with Gina Turrigiano, we discovered a form of homeostatic plasticity called synaptic scaling. Over the years we have collaborated with Gina's lab on mechanisms and functions of synaptic scaling. Currently, we are interested in the idea that homeostatic plasticity, which is normally beneficial to circuit function, can become maladaptive, leading to disorders like epilepsy. We have identified a set of transcription factors regulated by neuronal activity that control the magnitude of homeostatic responses. Loss of these transcription factors leads to epilepsy. We are investigating the target genes involved and their cellular and synaptic functions
Transcriptional and circuit mechanisms of gustatory learning
We are collaborating with Don Katz' lab to understand the cellular and molecular mechanisms contributing to Conditioned Taste Aversion, a robust form of one-trial learning. We have found that learning requires transcription within the basolateral amygdala (BLA), and used RNAseq to identify learning related transcripts in BLA projection neurons. To determine which transcripts are necessary for learning, we conditionally delete them selectively in BLA neurons using viruses and mouse genetics. Genetically and virally encoded reporter alleles allow us to identify neurons activated during learning, so that we can selectively probe their electrophysiology. These experiments have revealed changes in cellular excitability that are blocked by genetic manipulations that block learning.