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Week 4: BLA Neurons and Memory Trace

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Overall, both of these papers made me strongly consider the role of interneurons in the expression of fear behavior. Han et al 2015 mentioned at the end of their paper that the competition of neurons could be mediated in part by disynaptic competition on other pyramidal cells. From a recent review written by Elizabeth Lucas and Roger Clem from Mount Sinai medical school, they propose the narrative that interneurons play an active role in remodeling and that inhibition and disinhibition are necessary for fear-related behaviors. Given that both of these papers from the Sheena lab indicate that recent pyramidal excitability is necessary to recruit neurons in a memory trace in fear training. I’d be interested to see if there’s could be a way to determine the role of interneuron subtypes in this excitability mediated memory recruitment. For a simple test of the role of GABA in this process, one could utilize the same experimental design with the CREB and fear conditioning but put a GABA receptor antagonist on board and see how that affects the behavioral output.

It would be difficult to modify two distinct neuronal populations; the later Sheena lab paper utilized non-cre animals. To begin to parse out subtypes, maybe these experiments could be done in PV or SST knockout animals. I’d be worried about the broad effects of knocking out these cell types and the impact on fear learning in general, so perhaps a region-specific modulation using a PV or SST specific viral vector might be useful. The Dimidschstein lab at the Broad has a new PV-specific virus that could be utilized to drive an opsin in PV cells while overexpressing CREB in the BLA. While the tool may not be ideal for the BLA, I believe there is a BLA specific virus from the Allen Institute. Regardless, I believe that there could be a way to manipulate the activity of interneuron subtypes while overexpressing CREB to determine if interneurons are involved in the competition of pyramidal cells.  I’d be really fascinated to see if there’s a way to parse out the microcircuits involved in this excitatory driven cell competition for memory trace in fear learning.

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