Impaired fast-spiking interneuron function in a genetic mouse model of depression

Abstract
Article and author information
Metrics

Abstract

Rhythmic neuronal activity provides a frame for information coding by co-active cell assemblies. Abnormal brain rhythms are considered as potential pathophysiological mechanisms causing mental disease, but the underlying network defects are largely unknown. We find that mice expressing truncated Disrupted-in-Schizophrenia 1 (Disc1), which mirror a high-prevalence genotype for human psychiatric illness, show depression-related behavior. Theta and low-gamma synchrony in the prelimbic cortex (PrlC) is impaired in Disc1 mice and inversely correlated with the extent of behavioural despair. While weak theta activity is driven by the hippocampus, disturbance of low-gamma oscillations is caused by local defects of parvalbumin (PV)-expressing fast-spiking interneurons (FS-INs). The number of FS-INs is reduced, they receive fewer excitatory inputs, and form fewer release sites on targets. Computational analysis indicates that weak excitatory input and inhibitory output of FS-INs may lead to impaired gamma oscillations. Our data link network defects with a gene mutation underlying depression in humans.

Article and author information

Author details

Jonas-Frederic Sauer

Physiologisches Institut I, Systemic and Cellular Neurophysiology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany

Competing interests
No competing interests declared.
Michael Strüber

Physiologisches Institut I, Systemic and Cellular Neurophysiology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany

Competing interests
No competing interests declared.
Marlene Bartos

Physiologisches Institut I, Systemic and Cellular Neurophysiology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany

For correspondence
marlene.bartos@physiologie.uni-freiburg.de

Competing interests
Marlene Bartos, Reviewing editor, eLife.

Ethics

Animal experimentation: All in vivo and in vitro examinations were performed in agreement with national legislation and institutional regulations (license nr: G-13/25; X-10/18S) approved by the 'Regierungspräsidium' Freiburg.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.