Inhibitory control of the excitatory/inhibitory balance in psychiatric disorders.

Martijn Selten,Nael Nadif Kasri,Hans Van Bokhoven

doi:10.12688/f1000research.12155.1

Abstract

Neuronal networks consist of different types of neurons that all play their own role in order to maintain proper network function. The two main types of neurons segregate in excitatory and inhibitory neurons, which together regulate the flow of information through the network. It has been proposed that changes in the relative strength in these two opposing forces underlie the symptoms observed in psychiatric disorders, including autism and schizophrenia. Here, we review the role of alterations to the function of the inhibitory system as a cause of psychiatric disorders. First, we explore both patient and post-mortem evidence of inhibitory deficiency. We then discuss the function of different interneuron subtypes in the network and focus on the central role of a specific class of inhibitory neurons, parvalbumin-positive interneurons. Finally, we discuss genes known to be affected in different disorders and the effects that mutations in these genes have on the inhibitory system in cortex and hippocampus. We conclude that alterations to the inhibitory system are consistently identified in animal models of psychiatric disorders and, more specifically, that mutations affecting the function of parvalbumin-positive interneurons seem to play a central role in the symptoms observed in these disorders.

Highlights

Psychiatric disorders, including autism, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD) and depression, affect millions of people and are a major socio-economic burden[1,2,3]
Psychiatric disorders are a diverse group of disorders, but changes to the inhibitory system seem to be a point of convergence
Impairment of normal inhibitory function can arise from input to, output from, or intrinsic properties of inhibitory neurons

Summary

Introduction

Psychiatric disorders, including autism, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD) and depression, affect millions of people and are a major socio-economic burden[1,2,3]. Selective removal of Mecp[2] from SOM interneurons recapitulates part of the Rett syndrome phenotypes[168], and selective removal of Mecp[2] from either PV interneurons or SOM interneurons has been reported to cause circuit-wide deficits in information processing[169] From these studies, a picture is emerging in which excitatory inputs onto PV interneurons are found to be altered in different psychiatric disorders, leading to a reduced activity of these neurons and thereby tilting the E/I balance towards excitation. Mice carrying mutations in Nrxn1β show a reduced frequency of both inhibitory and excitatory input onto cortical pyramidal neurons[225] suggestive of a reduced number of synaptic contacts These studies show that neuroligin and neurexin mutations that are linked to autism affect the inhibitory system, including perisomatic-targeting interneurons. Changes to the inhibitory drive of PV interneurons can be caused by changes affecting the input, output or intrinsic properties of PV interneurons, and animal models of various psychiatric disorders all show alterations to one or more of these aspects, tilting the E/I balance

Conclusions

10. Marín O

33. Wong M

Findings

PubMed Abstract