How does our spatial memory system recognize changes in the environment? I perform chronic in vivo tetrode recordings of principal neurons in mouse hippocampus while manipulating the firing rate of upstream neurons in medial entorhinal cortex layer II. We revealed a novel role for grid cells in signaling contextual change to the hippocampus: the relationships between individual grid fields are stable over time, but can change independently. These rate changes in grid fields are sufficient to drive remapping of hippocampal place cells. Ongoing studies are systematically comparing the input-output relationships of CA3 and CA1 place cells to understand how these regions differentially transform sensory input, leading to unique functional roles in memory.
I delayed entering graduate school for two years to explore a different area of neuroscience and increase my skill set. I studied how protein kinase C-epsilon (PKCe) in the prefrontal cortex controls the extinction of both conditioned drug seeking and conditioned fear in mice. I used transgenic PKCe knockout mice, knocked down PKCe in infralimbic cortex with lentiviral vectors, or activated PKCe via systemic enzymes, and then performed a variety of behavioral assays. We found that mice lacking PKCe had delayed extinction of conditioned drug seeking for multiple drugs of abuse, and delayed extinction of conditioned fear. They were also impaired in reversal learning, suggesting that normal PKCe signaling in prefrontal cortex is required for updating cue-outcome associations.
In a separate line of research, I worked with a postdoc investigating the role of a unique enzyme, PKMzeta, in memory maintenance. PKMzeta has been hailed as "the memory molecule" due to some amazing studies showing that it is required for LTP maintenance and long-term memory. Surprisingly, we found that mice completely lacking this molecule had normal LTP, learning, and memory, indicating that PKMzeta is perhaps not the only molecule with a privileged role in memory.
My undergraduate research modeled the relational memory deficits observed in human patients with schizophrenia. I tested transgenic knockout mice lacking D-serine and mice with anatomical lesions of hippocampus or prefrontal cortex on behavioral memory tasks such as transitive inference and novel object recognition. Our primary finding was that both the hippocampus and prefrontal cortex are critical for different components of relational memory.