Authors

Katelyn N. Benthall,1,4 Katherine R. Cording,2,4 Alexander H.C.W. Agopyan-Miu,1 Corinna D. Wong,1 Emily Y. Chen,1 and Helen S. Bateup1,2,3,5,*

Affiliations

1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
2Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA
3Chan Zuckerberg Biohub, San Francisco, CA 94158, USA
4These authors contributed equally
5Lead contact
*Correspondence: [email protected]

Topic

Neuroscience, Optogenetics

Abstract

Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder that often presents with psychiatric conditions, including autism spectrum disorder (ASD). ASD is characterized by restricted, repetitive, and inflexible behaviors, which may result from abnormal activity in striatal circuits that mediate motor learning and action selection. To test whether altered striatal activity contributes to aberrant motor behaviors in the context of TSC, we conditionally deleted Tsc1 from direct or indirect pathway striatal projection neurons (dSPNs or iSPNs, respectively). We find that dSPN-specific loss of Tsc1 impairs endocannabinoid-mediated long-term depression (eCB-LTD) at cortico-dSPN synapses and strongly enhances corticostriatal synaptic drive, which is not observed in iSPNs. dSPN-Tsc1 KO, but not iSPN-Tsc1 KO, mice show enhanced motor learning, a phenotype observed in several mouse models of ASD. These findings demonstrate that dSPNs are particularly sensitive to Tsc1 loss and suggest that enhanced corticostriatal activation may contribute to altered motor behaviors in TSC.

DOI: https://dx.doi.org/10.1016%2Fj.celrep.2021.109511

Extract

For corticostriatal excitability experiments, optogenetic stimulation consisted of a full-field pulse of blue light (470 nm, 0.05 ms for iSPNs or 0.5 ms for dSPNs, CoolLED) through a 63x objective.

Product Associated Features

The simple and controllable single-wavelength pE-100 Illumination System is ideal for fluorescence screening applications.

Product Type

pE-100

Journal

Cell Reports

Year of Publication

2021

Country of Publication

USA