Title: Control of contextual memory through interneuronal a5-GABAA receptors
Legend: A. Behavioral paradigm used to assess learning. B. Etomidate (7mg/kg IP) reduced freezing (a proxy for memory) in pseudo-wild type mice (p-WT) but not in mice lacking a5-GABAARs in interneurons (a5-i-KO). C. GCaMP6f imaging used to measure dorsal hippocampal CA1 pyramidal neuron activity in freely exploring mice. D,E. Etomidate reduced the population vector (PV) correlation between spatially modulated firing activity in PM vs AM session (a neural correlate of memory) in p-WT but not in a5-i-KO mice. Dotted line in panel D shows time-shuffled null distribution.
Citation: Control of contextual memory through interneuronal a5-GABAA receptors. M Zhu, A Abdulzahir, MG Perkins, BM Krause, R Lennertz, D Ruhl, H Hentschke, R Nagarajan, ER Chapman, U Rudolph, MS Fanselow, RA Pearce. Manuscript under review (Feb 2022)
Abstract: g-aminobutyric acid type A receptors that incorporate a5 subunits (a5-GABAARs) are highly enriched in the hippocampus and they are strongly implicated in the control of learning and memory. Receptors located on pyramidal neuron dendrites have long been considered responsible, but here we report that selective elimination of a5-GABAARs from interneurons prevented the general anesthetic etomidate from suppressing contextual learning and from interfering with the development of place cells and spatial engrams in freely exploring mice. These findings implicate interneuronal a5-GABAARs in anesthetic-induced amnesia.
About the Lab: Research in the Pearce laboratory is focused on the mechanisms by which general anesthetics alter brain function. We are particularly interested in understanding how modulation of GABAA receptors impairs memory – a fundamental endpoint of anesthesia. For our studies we utilize expressed recombinant receptors and hippocampal brain slices to investigate the roles of specific subunit combinations and cell types in the control of learning and memory.