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Your search keyword '"Krauss, Jeremy M."' showing total 3 results
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2. Cerebellum-Specific Deletion of the GABAAReceptor δ Subunit Leads to Sex-Specific Disruption of Behavior

Author

Rudolph, Stephanie, Guo, Chong, Pashkovski, Stan L., Osorno, Tomas, Gillis, Winthrop F., Krauss, Jeremy M., Nyitrai, Hajnalka, Flaquer, Isabella, El-Rifai, Mahmoud, Datta, Sandeep Robert, and Regehr, Wade G.

Abstract

Granule cells (GCs) of the cerebellar input layer express high-affinity δ GABAAsubunit-containing GABAAreceptors (δGABAARs) that respond to ambient GABA levels and context-dependent neuromodulators like steroids. We find that GC-specific deletion of δGABAA(cerebellar [cb] δ knockout [KO]) decreases tonic inhibition, makes GCs hyperexcitable, and in turn, leads to differential activation of cb output regions as well as many cortical and subcortical brain areas involved in cognition, anxiety-like behaviors, and the stress response. Cb δ KO mice display deficits in many behaviors, but motor function is normal. Strikingly, δGABAAdeletion alters maternal behavior as well as spontaneous, stress-related, and social behaviors specifically in females. Our findings establish that δGABAARs enable the cerebellum to control diverse behaviors not previously associated with the cerebellum in a sex-dependent manner. These insights may contribute to a better understanding of the mechanisms that underlie behavioral abnormalities in psychiatric and neurodevelopmental disorders that display a gender bias.

Published
2020
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3. Cerebellum-Specific Deletion of the GABA A Receptor δ Subunit Leads to Sex-Specific Disruption of Behavior.

Author

Rudolph S, Guo C, Pashkovski SL, Osorno T, Gillis WF, Krauss JM, Nyitrai H, Flaquer I, El-Rifai M, Datta SR, and Regehr WG

Subjects
Animals, Anxiety pathology, Behavior, Animal, Female, Learning, Male, Maternal Behavior, Mice, Inbred C57BL, Mice, Knockout, Motor Activity, Organ Specificity, Stress, Psychological, Cerebellum metabolism, Gene Deletion, Protein Subunits metabolism, Receptors, GABA-A metabolism, Sex Characteristics
Abstract

Granule cells (GCs) of the cerebellar input layer express high-affinity δ GABA A subunit-containing GABA A receptors (δGABA A Rs) that respond to ambient GABA levels and context-dependent neuromodulators like steroids. We find that GC-specific deletion of δGABA A (cerebellar [cb] δ knockout [KO]) decreases tonic inhibition, makes GCs hyperexcitable, and in turn, leads to differential activation of cb output regions as well as many cortical and subcortical brain areas involved in cognition, anxiety-like behaviors, and the stress response. Cb δ KO mice display deficits in many behaviors, but motor function is normal. Strikingly, δGABA A deletion alters maternal behavior as well as spontaneous, stress-related, and social behaviors specifically in females. Our findings establish that δGABA A Rs enable the cerebellum to control diverse behaviors not previously associated with the cerebellum in a sex-dependent manner. These insights may contribute to a better understanding of the mechanisms that underlie behavioral abnormalities in psychiatric and neurodevelopmental disorders that display a gender bias., Competing Interests: Declaration of Interests S.R.D. is on the scientific advisory board of RBNC Inc., which has licensed the MoSeq technology, and holds patents related to the use of MoSeq to characterize behavior for drug development., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2020
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