Decreasing GABA function within the medial prefrontal cortex or basolateral amygdala decreases sociability

Abstract

Introduction Decreased sociability is a symptom of psychiatric conditions including autism-spectrum disorder and schizophrenia. Both of these conditions are associated with decreases in GABA function, particularly in the medial prefrontal cortex (PFC) and the basolateral amygdala (BLA); structures that are components of the social brain. Here, we determined if decreasing GABA transmission within either the PFC or the BLA decreases social behavior. Methods Rats were implanted with cannulae aimed at either the medial PFC or the BLA and then were tested on up to 4 behavioral tests following bilateral infusions of 0.5 μl bicuculline methiodide (BMI, a GABAA receptor antagonist) at doses of 0, 25, or 50 ng/μl. Rats were tested in the social interaction test, the social preference test, the sucrose preference test and for locomotor activity (BLA infusions only). Results Intra-BLA or PFC BMI infusions decreased the amount of time and the number of social interactions in the social interaction test. Further, in the social preference test, rats infused with 50 ng BMI no longer exhibited a preference to explore a social over a non-social stimulus. The change in sociability was not due to a change in reward processing or locomotor behavior. Discussion Decreasing GABA transmission in either the medial PFC or BLA decreased sociability. Thus, changes in GABA signaling observed in conditions such as autism or schizophrenia may mediate the social withdrawal characteristic of these conditions. Moreover, they suggest that social withdrawal may be treated by drugs that potentiate GABA transmission.

The Default Mode Network in Autism

“…During early embroyonic development, GABAergic interneurons are involved with regulating cell migration, differentiation, and synapse formation (112). Rodent models suggest that decreasing GABA transmission in the mPFC decreases sociability (113), consistent with our view that E/I imbalance in the DMN can contribute to impaired social function in autism.…”

Abnormalities in perineuronal nets and behavior in mice lacking CSGalNAcT1, a key enzyme in chondroitin sulfate synthesis

“…It is also recently reported that decreased GABAergic functions induce the sociability [ 14 ], which may be involved in the changes of our results concerning social interaction and preference (Fig. 4e-f ), as models of human autism-spectrum and schizophrenia [ 15 – 17 ].…”

Mammalian TRIM67 Functions in Brain Development and Behavior

“…Mice were evaluated for the effects of Trim67 deficiency on social preference using a 3-chamber choice test. This behavior has been associated with the hippocampus and parts of the amygdala ( Felix-Ortiz and Tye, 2014 ; Paine et al, 2017 ), both of which were decreased in size in Trim67 −/− brains. In the initial habituation phase, both Trim67 +/+ and Trim67 −/− mice made similar numbers of entries into each side chamber ( Trim67 +/+ ; 10.3 ± 1 right, 9.3 ± 0.7 left: Trim67 −/− ; 8.5 ± 0.9 right, 8.3 ± 0.8 left).…”