Prenatal disruption of D1R-SynGAP complex causes cognitive deficits in adulthood

Terence K Y Lai; Andrew R Abela; Ping Su; Paul J Fletcher; Fang Liu

doi:10.1016/j.pnpbp.2020.110122

Prenatal disruption of D1R-SynGAP complex causes cognitive deficits in adulthood

Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 8:105:110122. doi: 10.1016/j.pnpbp.2020.110122. Epub 2020 Oct 8.

Authors

Terence K Y Lai¹, Andrew R Abela², Ping Su³, Paul J Fletcher⁴, Fang Liu⁵

Affiliations

¹ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, M5T 1R8, Canada; Department of Physiology, Medical Sciences Building, 3rd Floor University of Toronto, 1 King's College Circle, M5S 1A8, Canada.
² Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, M5T 1R8, Canada; Psychiatry, 250 College Street, 8th floor, Toronto, Ontario, M5T 1R8, Canada.
³ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, M5T 1R8, Canada.
⁴ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, M5T 1R8, Canada; Psychiatry, 250 College Street, 8th floor, Toronto, Ontario, M5T 1R8, Canada; Psychology, 4th Floor, Sidney Smith Hall, 100 St. George Street, Toronto, Ontario, M5S 3G3, Canada.
⁵ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, M5T 1R8, Canada; Department of Physiology, Medical Sciences Building, 3rd Floor University of Toronto, 1 King's College Circle, M5S 1A8, Canada; Psychiatry, 250 College Street, 8th floor, Toronto, Ontario, M5T 1R8, Canada; Institutes of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: fang.liu@camh.ca.

PMID: 33039433
DOI: 10.1016/j.pnpbp.2020.110122

Abstract

γ-aminobutyric acid (GABA)-ergic interneurons are essential for the physiological function of the mammalian central nervous system. Dysregulated GABAergic interneuron function has been implicated in the pathophysiology of a number of neurodevelopmental disorders including schizophrenia and autism spectrum disorder. Tangential migration is an important process to ensure the proper localization of GABAergic interneurons. Previously we found that disrupting the interaction between dopamine D1 receptor (D1R) and synaptic Ras GTPase- activating protein (SynGAP) using an interfering peptide (TAT-D₁R_pep) during embryonic development impaired tangential migration. Here, we assessed the effects of prenatal disruption of D1R-SynGAP complex with the TAT-D₁R_pep on the expression of several behaviours during adulthood. Mice with prenatal D1R-SynGAP disruption exhibited transiently reduced locomotor activity, abnormal sensorimotor gating, impaired sociability and deficits in visual discrimination associative learning compared to their control counterparts. Our findings reinforce the importance of GABAergic interneuron migration in the manifestation of normal motor, sensory, and cognitive behaviours of animals during adulthood.

Keywords: Dopamine D1 receptor; GABAergic interneuron migration; Sociability; Synaptic Ras GTPase-activating protein (SynGAP); Visual discriminative learning.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cognition / physiology*
Embryonic Development / genetics
Interneurons / metabolism
Male
Mice
Motor Activity / genetics*
Receptors, Dopamine D1 / genetics*
Receptors, Dopamine D1 / metabolism
Sensory Gating / genetics
ras GTPase-Activating Proteins / genetics*
ras GTPase-Activating Proteins / metabolism

Substances

Receptors, Dopamine D1
Syngap1 protein, mouse
ras GTPase-Activating Proteins