Dorsomedial striatal neuroinflammation causes excessive goal-directed action control by disrupting astrocyte function.

Abiero, AR; Gladding, JM; Iredale, JA; Drury, HR; Manning, EE; Dayas, CV; Dhungana, A; Ganesan, K; Turner, K; Becchi, S; Kendig, MD; Nolan, C; Balleine, B; Castorina, A; Cole, L; Clemens, KJ; Bradfield, LA

Dorsomedial striatal neuroinflammation causes excessive goal-directed action control by disrupting astrocyte function.

Abiero, AR Gladding, JM Iredale, JA Drury, HR Manning, EE Dayas, CV Dhungana, A Ganesan, K Turner, K Becchi, S Kendig, MD Nolan, C Balleine, B Castorina, A

Cole, L Clemens, KJ Bradfield, LA

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Publisher:: SPRINGERNATURE
Publication Type:: Journal Article
Citation:: Neuropsychopharmacology, 2025
Issue Date:: 2025-09-27

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Field	Value	Language
dc.contributor.author	Abiero, AR
dc.contributor.author	Gladding, JM
dc.contributor.author	Iredale, JA
dc.contributor.author	Drury, HR
dc.contributor.author	Manning, EE
dc.contributor.author	Dayas, CV
dc.contributor.author	Dhungana, A
dc.contributor.author	Ganesan, K
dc.contributor.author	Turner, K
dc.contributor.author	Becchi, S
dc.contributor.author	Kendig, MD
dc.contributor.author	Nolan, C
dc.contributor.author	Balleine, B
dc.contributor.author	Castorina, A https://orcid.org/0000-0001-7037-759X
dc.contributor.author	Cole, L
dc.contributor.author	Clemens, KJ
dc.contributor.author	Bradfield, LA
dc.date.accessioned	2025-10-15T04:13:36Z
dc.date.available	2025-09-12
dc.date.available	2025-10-15T04:13:36Z
dc.date.issued	2025-09-27
dc.identifier.citation	Neuropsychopharmacology, 2025
dc.identifier.issn	0893-133X
dc.identifier.issn	1740-634X
dc.identifier.uri	http://hdl.handle.net/10453/190480
dc.description.abstract	Compulsive actions are typically thought to reflect the dominance of habits over goal-directed action. To investigate this, we mimicked the striatal neuroinflammation that is frequently exhibited in individuals with compulsive disorders in rats, by injecting the endotoxin lipopolysaccharide into the posterior dorsomedial striatum, and assessed the consequences for behavioural control. Surprisingly, this manipulation caused rats to acquire and maintain goal-directed actions under conditions that would otherwise produce habits. Immunohistochemical analyses indicated that these behaviours were a result of astrocytic proliferation. To probe this further, we chemogenetically activated the Gi-pathway in striatal astrocytes, which altered the firing properties of nearby medium spiny neurons and modulated goal-directed action control. Together, results show that striatal neuroinflammation is sufficient to bias action selection toward excessive goal-directed control via dysregulated astrocyte function. If translatable, our findings suggest that, contrary to conventional views, individuals with striatal neuroinflammation might be more prone to maladaptive goal-directed actions than habits, and future interventions should aim to restore appropriate action control.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	SPRINGERNATURE
dc.relation	http://purl.org/au-research/grants/arc/DP200102445
dc.relation	http://purl.org/au-research/grants/nhmrc/2003346
dc.relation.ispartof	Neuropsychopharmacology
dc.relation.isbasedon	10.1038/s41386-025-02247-4
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences
dc.subject.classification	Psychiatry
dc.subject.classification	3209 Neurosciences
dc.subject.classification	5202 Biological psychology
dc.title	Dorsomedial striatal neuroinflammation causes excessive goal-directed action control by disrupting astrocyte function.
dc.type	Journal Article
utslib.location.activity	England
utslib.for	11 Medical and Health Sciences
utslib.for	17 Psychology and Cognitive Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Stroke Research Collaborative
pubs.organisational-group	University of Technology Sydney/UTS Groups/Chancellor's Research Fellows
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2025-10-15T04:13:31Z
pubs.publication-status	Published online

Abstract:

Compulsive actions are typically thought to reflect the dominance of habits over goal-directed action. To investigate this, we mimicked the striatal neuroinflammation that is frequently exhibited in individuals with compulsive disorders in rats, by injecting the endotoxin lipopolysaccharide into the posterior dorsomedial striatum, and assessed the consequences for behavioural control. Surprisingly, this manipulation caused rats to acquire and maintain goal-directed actions under conditions that would otherwise produce habits. Immunohistochemical analyses indicated that these behaviours were a result of astrocytic proliferation. To probe this further, we chemogenetically activated the Gi-pathway in striatal astrocytes, which altered the firing properties of nearby medium spiny neurons and modulated goal-directed action control. Together, results show that striatal neuroinflammation is sufficient to bias action selection toward excessive goal-directed control via dysregulated astrocyte function. If translatable, our findings suggest that, contrary to conventional views, individuals with striatal neuroinflammation might be more prone to maladaptive goal-directed actions than habits, and future interventions should aim to restore appropriate action control.

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http://hdl.handle.net/10453/190480