Journal Article

Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons

Song, L J, Padilla-Coreano, N, Harrison, N L, Gordon, J A, Brown, A, Canetta, S, Sahn, R, Kellendonk, C, Bolkan, S

2016

Overview

Abnormalities in prefrontal gamma aminobutyric acid (GABA)ergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders, including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, resulted from a decrease in release probability and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to MIA, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/21 / 14/63 / 631/378 / 64/60 / 692/699/476 / 82/51 / Analysis / Animal models / Animals / Anxiety / Anxiety disorders / Behavioral Sciences / Biological Psychology / Bipolar disorder / Calretinin / Cognitive ability / Disease Models, Animal / Epidemiology / Female / GABAergic Neurons - metabolism / gamma-Aminobutyric Acid / Humans / Immune response / Immunity, Active / Inhibition, Psychological / Interneurons / Interneurons - metabolism / Male / Medicine / Medicine & Public Health / Memory, Short-Term - physiology / Mental disorders / Mice / Neurosciences / Neurotransmission / Offspring / original-article / Oscillations / Parvalbumin / Parvalbumins - immunology / Parvalbumins - metabolism / Pathophysiology / Pharmacotherapy / Physiology, Pathological / Prefrontal cortex / Prefrontal Cortex - metabolism / Pregnancy / Prenatal Exposure Delayed Effects / Psychiatry / Risk factors / Schizophrenia / Short term memory / Synaptic Transmission - immunology / Synaptic Transmission - physiology / γ-Aminobutyric acid