Dopamine D1 Receptor-Positive Neurons in the Lateral Nucleus of the Cerebellum Contribute to Cognitive Behavior

Biological Psychiatry
Timothy M LockeErik S Carlson

Abstract

Studies in humans and nonhuman primates have identified a region of the dentate nucleus of the cerebellum, or the lateral cerebellar nucleus (LCN) in rodents, activated during performance of cognitive tasks involving complex spatial and sequential planning. Whether such a subdivision exists in rodents is not known. Dopamine and its receptors, which are implicated in cognitive function, are present in the cerebellar nuclei, but their function is unknown. Using viral and genetic strategies in mice, we examined cellular phenotypes of dopamine D1 receptor-positive (D1R+) cells in the LCN with whole-cell patch clamp recordings, messenger RNA profiling, and immunohistochemistry to examine D1R expression in mouse LCN and human dentate nucleus of the cerebellum. We used chemogenetics to inhibit D1R+ neurons and examined behaviors including spatial navigation, social recognition memory, prepulse inhibition of the acoustic startle reflex, response inhibition, and working memory to test the necessity of these neurons in these behaviors. We identified a population of D1R+ neurons that are localized to an anatomically distinct region of the LCN. We also observed D1R+ neurons in human dentate nucleus of the cerebellum, which suggests an evol...Continue Reading

Citations

Mar 1, 2019·Pharmacological Reviews·Annika Højrup RunegaardUlrik Gether
Jul 30, 2019·Frontiers in Physiology·Lin LiGao-Xia Wei
Sep 11, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Hirofumi Fujita, Erik S Carlson
Aug 28, 2020·Frontiers in Cellular Neuroscience·Timothy M LockeErik S Carlson
Mar 16, 2021·Frontiers in Behavioral Neuroscience·Evelyn M Guilherme, Anna Carolyna L Gianlorenço
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tim J FyfeBen Capuano
Jul 9, 2021·Annual Review of Neuroscience·Catherine J Stoodley, Peter T Tsai
Aug 21, 2021·Scientific Reports·G HorvathS Benyhe
Jul 12, 2020·Neuroscience·Ayesha R ThanawallaEiman Azim
Aug 24, 2021·Frontiers in Systems Neuroscience·Paolo FlaceGiuseppe Anastasi
Sep 21, 2021·ELife·Elena N JuddAbigail L Person

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