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ORIGINAL RESEARCH article

Front. Cell. Neurosci.
Sec. Cellular Neurophysiology
Volume 18 - 2024 | doi: 10.3389/fncel.2024.1415015

Sex differences in the distribution and density of regulatory interneurons in the striatum

Provisionally accepted
Meghan Van Zandt Meghan Van Zandt 1,2*Deirdre Flanagan Deirdre Flanagan 1,2Christopher Pittenger Christopher Pittenger 1,2,3,4,5,6*
  • 1 Department of Psychiatry, School of Medicine, Yale University, New Haven, Connecticut, United States
  • 2 Yale University, New Haven, United States
  • 3 Child Study Center, School of Medicine, Yale University, New Haven, Connecticut, United States
  • 4 Department of Psychology, Faculty of Arts and Sciences, Yale University, New Haven, Connecticut, United States
  • 5 Center for Brain and Mind Health, School of Medicine, Yale University, New Haven, Connecticut, United States
  • 6 Wu Tsai Institute, Yale University, New Haven, Connecticut, United States

The final, formatted version of the article will be published soon.

    Dysfunction of the cortico-basal circuitry -including its primary input nucleus, the striatumcontributes to neuropsychiatric disorders, such as autism and Tourette Syndrome (TS). These conditions show marked sex differences, occurring more often in males than in females. Regulatory interneurons, such as cholinergic interneurons (CINs) and parvalbumin-expressing GABAergic fast spiking interneurons (FSIs), are implicated in human neuropsychiatric disorders such as TS, and ablation of these interneurons produces relevant behavioral pathology in male mice, but not in females.Here we investigate sex differences in the density and distribution of striatal interneurons, using stereological quantification of CINs, FSIs, and somatostatin-expressing (SOM) GABAergic interneurons in the dorsal striatum (caudate-putamen) and the ventral striatum (nucleus accumbens) in male and female mice. Males have a higher density of CINs than females, especially in the dorsal striatum; females have equal distribution between dorsal and ventral striatum. FSIs showed similar distributions, with a greater dorsal-ventral density gradient in males than in females. SOM interneurons were denser in the ventral than in the dorsal striatum, with no sex differences. These sex differences in the density and distribution of FSIs and CINs may contribute to sex differences in basal ganglia function, particularly in the context of psychopathology.

    Keywords: sex differences, Interneurons, Striatum, parvalbumin, GABAergic, cholinergic, Basal Ganglia

    Received: 09 Apr 2024; Accepted: 25 Jun 2024.

    Copyright: © 2024 Van Zandt, Flanagan and Pittenger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Meghan Van Zandt, Department of Psychiatry, School of Medicine, Yale University, New Haven, 06511, Connecticut, United States
    Christopher Pittenger, Yale University, New Haven, United States

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