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Perineuronal Nets in the Dorsomedial Striatum Contribute to Behavioral Dysfunction in Mouse Models of Excessive Repetitive Behavior

Authors
  • Briones, Brandy A.
  • Pitcher, Miah N.
  • Fleming, Weston T.
  • Libby, Alexandra
  • Diethorn, Emma J.
  • Haye, Amanda E.
  • MacDowell, Camden J.
  • Zych, Anna D.
  • Waters, Renée C.
  • Buschman, Timothy J.
  • Witten, Ilana B.
  • Gould, Elizabeth
Type
Published Article
Journal
Biological Psychiatry Global Open Science
Publisher
Elsevier
Publication Date
Nov 17, 2021
Volume
2
Issue
4
Pages
460–469
Identifiers
DOI: 10.1016/j.bpsgos.2021.11.005
PMID: 36324654
PMCID: PMC9616293
Source
PubMed Central
Keywords
Disciplines
  • Archival Report
License
Unknown

Abstract

Background Excessive repetitive behavior is a debilitating symptom of several neuropsychiatric disorders. Parvalbumin-positive inhibitory interneurons in the dorsal striatum have been linked to repetitive behavior, and a sizable portion of these cells are surrounded by perineuronal nets (PNNs), specialized extracellular matrix structures. Although PNNs have been associated with plasticity and neuropsychiatric disease, no previous studies have investigated their involvement in excessive repetitive behavior. Methods We used histochemistry and confocal imaging to investigate PNNs surrounding parvalbumin-positive cells in the dorsal striatum of 4 mouse models of excessive repetitive behavior (BTBR, Cntnap2, Shank3, prenatal valproate treatment). We then investigated one of these models, the BTBR mouse, in detail, with DiI labeling, in vivo and in vitro recordings, and behavioral analyses. We next degraded PNNs in the dorsomedial striatum (DMS) using the enzyme chondroitinase ABC and assessed dendritic spine density, electrophysiology, and repetitive behavior. Results We found a greater percentage of parvalbumin-positive interneurons with PNNs in the DMS of all 4 mouse models of excessive repetitive behavior compared with control mice. In BTBR mice, we found fewer dendritic spines on medium spiny neurons (targets of parvalbumin-positive interneurons) and differences in neuronal oscillations as well as inhibitory postsynaptic potentials compared with control mice. Reduction of DMS PNNs in BTBR mice altered dendritic spine density and inhibitory responses and normalized repetitive behavior. Conclusions These findings suggest that cellular abnormalities in the DMS are associated with maladaptive repetitive behaviors and that manipulating PNNs can restore normal levels of repetitive behavior while altering DMS dendritic spines and inhibitory signaling.

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