Journal article
Maternal Immune Activation Leads to Selective Functional Deficits in Offspring Parvalbumin Interneurons
Molecular psychiatry, Vol.21(7), pp.956-968
07/01/2016
DOI: 10.1038/mp.2015.222
PMCID: PMC4914410
PMID: 26830140
Abstract
Abnormalities in prefrontal GABAergic 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, 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 maternal immune activation, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders.
Details
- Title: Subtitle
- Maternal Immune Activation Leads to Selective Functional Deficits in Offspring Parvalbumin Interneurons
- Creators
- Sarah Canetta - Columbia University Irving Medical CenterScott Bolkan - Columbia University Irving Medical CenterNancy Padilla-Coreano - Columbia University Irving Medical CenterLouJin Song - Columbia University Irving Medical CenterRyan Sahn - Columbia University Irving Medical CenterNeil Harrison - Columbia University Irving Medical CenterJoshua A. Gordon - Columbia University Irving Medical CenterAlan Brown - Columbia University Irving Medical CenterChristoph Kellendonk - Columbia University Irving Medical Center
- Resource Type
- Journal article
- Publication Details
- Molecular psychiatry, Vol.21(7), pp.956-968
- DOI
- 10.1038/mp.2015.222
- PMID
- 26830140
- PMCID
- PMC4914410
- NLM abbreviation
- Mol Psychiatry
- ISSN
- 1359-4184
- eISSN
- 1476-5578
- Number of pages
- 13
- Language
- English
- Date published
- 07/01/2016
- Academic Unit
- Psychological and Brain Sciences
- Record Identifier
- 9984944742202771
Metrics
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