Journal
NEURON
Volume 109, Issue 16, Pages 2590-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2021.06.005
Keywords
-
Categories
Funding
- Stanley Center at the Broad Institute
- Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT
- James and Patricia Poitras Center for Psychiatric Disorders Research at MIT
- NIH BRAIN Initiative [U01MH114819]
- Medical Research Institute of TMDU
- NSF EAGER [2035018]
- Direct For Computer & Info Scie & Enginr
- Div Of Information & Intelligent Systems [2035018] Funding Source: National Science Foundation
Ask authors/readers for more resources
The study identified specific gene expressions in the anterior thalamic nuclei related to autism and schizophrenia, affecting memory functions. Different areas within the nuclei have distinct functions in memory encoding, with regulation of neuronal excitability playing a role in memory deficits. The findings suggest converging cellular mechanisms underlying cognitive deficits in certain neuropsychiatric disease models.
Neuropsychiatric disorders are often accompanied by cognitive impairments/intellectual disability (ID). It is not clear whether there are converging mechanisms underlying these debilitating impairments. We found that many autism and schizophrenia risk genes are expressed in the anterodorsal subdivision (AD) of anterior thalamic nuclei, which has reciprocal connectivity with learning and memory structures. CRISPR-Cas9 knockdown of multiple risk genes selectively in AD thalamus led to memory deficits. While the AD is necessary for contextual memory encoding, the neighboring anteroventral subdivision (AV) regulates memory specificity. These distinct functions of AD and AV are mediated through their projections to retrosplenial cortex, using differential mechanisms. Furthermore, knockdown of autism and schizophrenia risk genes PTCHD1, YWHAG, or HERC1 from AD led to neuronal hyperexcitability, and normalization of hyperexcitability rescued memory deficits in these models. This study identifies converging cellular to circuit mechanisms underlying cognitive deficits in a subset of neuropsychiatric disease models.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available