News Release

Key memory receptors are located on interneurons

Peer-Reviewed Publication

PNAS Nexus

Figure 3a  from Zhu et al.

image: Hippocampal dorsal CA1 pyramidal neuron activity was captured using a head-mounted miniaturized endoscope. Contours of five cells are overlayed on the maximum projected image from a 10-minute recording; their associated fluorescence traces are shown below. view more 

Credit: Zhu et al.

A key receptor regulating memory formation has been localized to interneurons, according to a study with implications for drug development. Robert Pearce and colleagues probed the localization of γ-aminobutyric acid type A receptors that incorporate α5 subunits (α5-GABAARs). α5-GABAARs are concentrated within the hippocampus, a brain structure that is essential for the formation of episodic memories. The general anesthetic etomidate blocks learning by targeting α5-GABAARs, as do many drugs designed to enhance cognition, intended for use in people with Alzheimer’s disease, Down syndrome, autism, depression, and schizophrenia. Researchers have assumed that these drugs act through α5-GABAARs on pyramidal neurons, but by monitoring the formation and stability of spatial memories directly within the hippocampus of mice, the authors found that selectively knocking α5-GABAARs out of interneurons rendered etomidate ineffective in blocking memory formation and impaired spatial memory overall. By contrast, knocking α5-GABAARs out of pyramidal neurons did not alter memory, and did not prevent etomidate from blocking spatial memories. The authors conclude that interneuronal α5-GABAARs serve a physiological role in promoting spatial learning, and serve as essential targets for etomidate modulation of contextual memory.

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