Back to Search
Start Over
Astrocyte-mediated regulation of BLA WFS1 neurons alleviates risk-assessment deficits in DISC1-N mice.
- Source :
-
Neuron [Neuron] 2024 Jul 03; Vol. 112 (13), pp. 2197-2217.e7. Date of Electronic Publication: 2024 Apr 19. - Publication Year :
- 2024
-
Abstract
- Assessing and responding to threats is vital in everyday life. Unfortunately, many mental illnesses involve impaired risk assessment, affecting patients, families, and society. The brain processes behind these behaviors are not well understood. We developed a transgenic mouse model (disrupted-in-schizophrenia 1 [DISC1]-N) with a disrupted avoidance response in risky settings. Our study utilized single-nucleus RNA sequencing and path-clamp coupling with real-time RT-PCR to uncover a previously undescribed group of glutamatergic neurons in the basolateral amygdala (BLA) marked by Wolfram syndrome 1 (WFS1) expression, whose activity is modulated by adjacent astrocytes. These neurons in DISC1-N mice exhibited diminished firing ability and impaired communication with the astrocytes. Remarkably, optogenetic activation of these astrocytes reinstated neuronal excitability via D-serine acting on BLA <superscript>WFS1</superscript> neurons' NMDA receptors, leading to improved risk-assessment behavior in the DISC1-N mice. Our findings point to BLA astrocytes as a promising target for treating risk-assessment dysfunctions in mental disorders.<br />Competing Interests: Declaration of interests L.W. is a member of the advisory board for Neuron.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Mice
Optogenetics
Membrane Proteins metabolism
Membrane Proteins genetics
Male
Risk-Taking
Disease Models, Animal
Mice, Inbred C57BL
Astrocytes metabolism
Mice, Transgenic
Neurons metabolism
Nerve Tissue Proteins genetics
Nerve Tissue Proteins metabolism
Basolateral Nuclear Complex metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 112
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 38642554
- Full Text :
- https://doi.org/10.1016/j.neuron.2024.03.028