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My 2nd PhD preprint is now out: https://www.biorxiv.org/content/10.1101/2021.01.04.425303v1. We found that different GABAergic neuron classes in CA3 & DG bidirectionally modulate internal and external drive measured in CA1. #tweeprint below! 1/11
Internal (from CA3) and external (from EC) inputs drive different aspects of memory processing, and so must be balanced to avoid interference. We posited that PV+ and SST+ interneurons are well positioned to regulate these 2 types of drive, respectively 2/11
Could interneurons in CA3 & DG affect CA1? Could these 2 classes (which have some overlap) lead to different responses? Would curtailing internal drive lead to an increase in external drive and vice versa? We set to find out! (Spoiler alert: yes to all 3) 3/11
We suppressed CA3 & DG PV+ or SST+ interneurons (via hM4D) and recorded LFP, which we used as a proxy for CA3 and EC drive. We hypothesized suppressing PV+ would increase CA3 drive, while suppressing SST+ would increase EC drive 4/11
As a gut check, we confirmed that suppressing either interneuron type led to an increase in local MUA. But, both change MUA in the same direction & don't affect CA1 MUA. Yet they still modulated CA1 LFP, in opposite directions 5/11
During rest, signatures of CA3 drive (e.g. ripple rate) increased following PV+ suppression and decreased following SST+ suppression 6/11
During running, signatures of CA3 drive (e.g. slow gamma) increased following PV+ suppression and decreased following SST+ suppression, while signatures of EC drive (e.g. fast gamma) decreased following PV+ suppression and increased following SST+ suppression 7/11
What about suppressing both types simultaneously? Same result as just suppressing PV+. Check it out, along with CA3 & DG LFP and many levels of controls, in the 6 supp. figures & 6 supp. tables 8/11
TLDR: we found suppressing CA3+DG PV+ interneurons ungates CA3 drive to CA1, while suppressing CA3+DG SST+ interneurons facilitates inputs from EC to DG+CA3 which in turn drives CA1 9/11
Balancing these inputs could control the switch between encoding and consolidation and have consequences for learning. Suppressing SST+ neurons matched findings from #Alzheimers models, which specifically lose SST+ neurons, suggesting a targetable, functional link 10/11
Coming soon (I hope) to a journal & data repo near you! For now, here's the code: https://github.com/emilyasterjones/interneurons_modulate_drive 11/11
