RRC ID 33627
著者 Bergeron SA, Carrier N, Li GH, Ahn S, Burgess HA.
タイトル Gsx1 expression defines neurons required for prepulse inhibition.
ジャーナル Mol Psychiatry
Abstract In schizophrenia, cognitive overload is thought to reflect an inability to suppress non-salient information, a process which is studied using prepulse inhibition (PPI) of the startle response. PPI is reduced in schizophrenia and routinely tested in animal models and preclinical trials of antipsychotic drugs. However, the underlying neuronal circuitry is not well understood. We used a novel genetic screen in larval zebrafish to reveal the molecular identity of neurons that are required for PPI in fish and mice. Ablation or optogenetic silencing of neurons with developmental expression of the transcription factor genomic screen homeobox 1 (gsx1) produced profound defects in PPI in zebrafish, and PPI was similarly impaired in Gsx1 knockout mice. Gsx1-expressing neurons reside in the dorsal brainstem and form synapses closely apposed to neurons that initiate the startle response. Surprisingly, brainstem Gsx1 neurons are primarily glutamatergic despite their role in a functionally inhibitory pathway. As Gsx1 has an important role in regulating interneuron development in the forebrain, these findings reveal a molecular link between control of interneuron specification and circuits that gate sensory information across brain regions.
巻・号 20(8)
ページ 974-85
公開日 2015-8-1
DOI 10.1038/mp.2014.106
PII mp2014106
PMID 25224259
PMC PMC4362800
MeSH Animals Animals, Genetically Modified Auditory Perception / physiology Brain / embryology Brain / physiology* Glutamic Acid / metabolism Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* In Situ Hybridization Mice, Knockout Microscopy, Confocal Microscopy, Fluorescence Neurons / physiology* Optogenetics Prepulse Inhibition / physiology* Reflex, Startle / physiology Zebrafish Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*
IF 12.384
引用数 20
WOS 分野 PSYCHIATRY BIOCHEMISTRY & MOLECULAR BIOLOGY NEUROSCIENCES
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