We recently reported that the competitive NMDAR antagonist (R,S)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) does not suppress NMDAR-mediated field EPSPs (fEPSPNMDA) or long-term potentiation (LTP) in vitro at concentrations that block contextual conditioning in vivo. Here we tested one possible explanation for the mismatch – that the hippocampus is relatively resistant to CPP compared to other brain structures engaged in contextual fear conditioning.
Since 2016, the Waisman Center has partnered with Lawrence University in Appleton, Wisconsin to provide summer research internships for undergraduate Lawrence students in the labs of Waisman researchers.
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.
Previous experiments using genetic and pharmacological manipulations have provided strong evidence that etomidate impairs synaptic plasticity and memory by modulating a5-subunit containing GABAARs (a5-GABAARs). Since a5-GABAARs mediate tonic inhibition (TI) in hippocampal CA1 pyramidal cells, and etomidate enhances TI, etomidate enhancement of TI in pyramidal cells has been proposed as the underlying mechanism (Martin et al., 2009).