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Dominant-Negative DISC1 Alters the Dopaminergic Modulation of Inhibitory Interneurons in the Mouse Prefrontal Cortex
- Source :
- Complex Psychiatry. 4:20-29
- Publication Year :
- 2018
- Publisher :
- S. Karger AG, 2018.
-
Abstract
- A truncated disrupted in schizophrenia 1 (Disc1) gene increases the risk of psychiatric disorders, probably affecting cortical interneurons. Here, we sought to determine whether this cell population is affected in mice carrying a truncated (Disc1) allele (DN-DISC1). We utilized whole cell recordings to assess electrophysiological properties and modulation by dopamine (DA) in two classes of interneurons: fast-spiking (FS) and low threshold-spiking (LTS) interneurons in wild-type and DN-DISC1 mice. In DN-DISC1 mice, FS interneurons, but not LTS interneurons, exhibited altered action potentials. Further, the perineuronal nets that surround FS interneurons exhibited abnormal morphology in DN-DISC1 mice, and the DA modulation of this cell type was altered in DN-DISC1 mice. We conclude that early-life manipulation of a gene associated with risk of psychiatric disease can result in dysfunction, but not loss, of specific GABAergic interneurons. The resulting alteration of excitatory-inhibitory balance is a critical element in DISC1 pathophysiology.
- Subjects :
- 0301 basic medicine
Original Paper
education.field_of_study
biology
musculoskeletal, neural, and ocular physiology
Perineuronal net
fungi
Population
General Medicine
Inhibitory postsynaptic potential
03 medical and health sciences
DISC1
030104 developmental biology
0302 clinical medicine
nervous system
Dopamine
biology.protein
medicine
GABAergic
Prefrontal cortex
education
Neuroscience
030217 neurology & neurosurgery
Parvalbumin
medicine.drug
Subjects
Details
- ISSN :
- 2673298X and 26733005
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Complex Psychiatry
- Accession number :
- edsair.doi.dedup.....d55dd28004007d011e2641ef3f36e316