Disinhibition, an emerging pharmacology of learning and memory

Hanns Möhler; Uwe Rudolph

doi:10.12688/f1000research.9947.1

Disinhibition, an emerging pharmacology of learning and memory

F1000Res. 2017 Feb 3:6:F1000 Faculty Rev-101. doi: 10.12688/f1000research.9947.1. eCollection 2017.

Authors

Hanns Möhler¹, Uwe Rudolph²

Affiliations

¹ Institute of Pharmacology, University of Zurich, Zurich, Switzerland; Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.
² Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.

Abstract

Learning and memory are dependent on interactive excitatory and inhibitory mechanisms. In this review, we discuss a mechanism called disinhibition, which is the release of an inhibitory constraint that effectively results in an increased activity in the target neurons (for example, principal or projection neurons). We focus on discussing the role of disinhibition in learning and memory at a basic level and in disease models with cognitive deficits and highlight a strategy to reverse cognitive deficits caused by excess inhibition, through disinhibition of α5-containing GABA _A receptors mediating tonic inhibition in the hippocampus, based on subtype-selective negative allosteric modulators as a novel class of drugs.

Keywords: GABAA; Pavlovian learning; allosteric modulators; disinhibition; somatostatin.

Publication types

Review

Grants and funding

UR was supported by grant R01GM086448 from the National Institute of General Medical Sciences and grant R01MH095905 from the National Institute of Mental Health, National Institutes of Health.