Cognitive effects of thalamostriatal degeneration are ameliorated by normalizing striatal cholinergic activity.

Becchi, S; Chieng, B; Bradfield, LA; Capellán, R; Leung, BK; Balleine, BW

Cognitive effects of thalamostriatal degeneration are ameliorated by normalizing striatal cholinergic activity.

Becchi, S Chieng, B Bradfield, LA Capellán, R Leung, BK Balleine, BW

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Publisher:: AMER ASSOC ADVANCEMENT SCIENCE
Publication Type:: Journal Article
Citation:: Sci Adv, 2023, 9, (25), pp. eade8247
Issue Date:: 2023-06-23

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Field	Value	Language
dc.contributor.author	Becchi, S
dc.contributor.author	Chieng, B
dc.contributor.author	Bradfield, LA
dc.contributor.author	Capellán, R
dc.contributor.author	Leung, BK
dc.contributor.author	Balleine, BW
dc.date.accessioned	2024-01-15T04:48:35Z
dc.date.available	2024-01-15T04:48:35Z
dc.date.issued	2023-06-23
dc.identifier.citation	Sci Adv, 2023, 9, (25), pp. eade8247
dc.identifier.issn	2375-2548
dc.identifier.issn	2375-2548
dc.identifier.uri	http://hdl.handle.net/10453/174450
dc.description.abstract	The loss of neurons in parafascicular thalamus (Pf) and their inputs to dorsomedial striatum (DMS) in Lewy body disease (LBD) and Parkinson's disease dementia (PDD) have been linked to the effects of neuroinflammation. We found that, in rats, these inputs were necessary for both the function of striatal cholinergic interneurons (CINs) and the flexible encoding of the action-outcome (AO) associations necessary for goal-directed action, producing a burst-pause pattern of CIN firing but only during the remapping elicited by a shift in AO contingency. Neuroinflammation in the Pf abolished these changes in CIN activity and goal-directed control after the shift in contingency. However, both effects were rescued by either the peripheral or the intra-DMS administration of selegiline, a monoamine oxidase B inhibitor that we found also enhances adenosine triphosphatase activity in CINs. These findings suggest a potential treatment for the cognitive deficits associated with neuroinflammation affecting the function of the Pf and related structures.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	AMER ASSOC ADVANCEMENT SCIENCE
dc.relation.ispartof	Sci Adv
dc.relation.isbasedon	10.1126/sciadv.ade8247
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Rats
dc.subject.mesh	Animals
dc.subject.mesh	Dementia
dc.subject.mesh	Neuroinflammatory Diseases
dc.subject.mesh	Cholinergic Neurons
dc.subject.mesh	Parkinson Disease
dc.subject.mesh	Corpus Striatum
dc.subject.mesh	Cholinergic Agents
dc.subject.mesh	Cognition
dc.subject.mesh	Corpus Striatum
dc.subject.mesh	Animals
dc.subject.mesh	Rats
dc.subject.mesh	Parkinson Disease
dc.subject.mesh	Dementia
dc.subject.mesh	Cholinergic Agents
dc.subject.mesh	Cognition
dc.subject.mesh	Cholinergic Neurons
dc.subject.mesh	Neuroinflammatory Diseases
dc.subject.mesh	Rats
dc.subject.mesh	Animals
dc.subject.mesh	Dementia
dc.subject.mesh	Neuroinflammatory Diseases
dc.subject.mesh	Cholinergic Neurons
dc.subject.mesh	Parkinson Disease
dc.subject.mesh	Corpus Striatum
dc.subject.mesh	Cholinergic Agents
dc.subject.mesh	Cognition
dc.title	Cognitive effects of thalamostriatal degeneration are ameliorated by normalizing striatal cholinergic activity.
dc.type	Journal Article
utslib.citation.volume	9
utslib.location.activity	United States
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
utslib.copyright.status	open_access	*
dc.date.updated	2024-01-15T04:48:27Z
pubs.issue	25
pubs.publication-status	Published
pubs.volume	9
utslib.citation.issue	25

Abstract:

The loss of neurons in parafascicular thalamus (Pf) and their inputs to dorsomedial striatum (DMS) in Lewy body disease (LBD) and Parkinson's disease dementia (PDD) have been linked to the effects of neuroinflammation. We found that, in rats, these inputs were necessary for both the function of striatal cholinergic interneurons (CINs) and the flexible encoding of the action-outcome (AO) associations necessary for goal-directed action, producing a burst-pause pattern of CIN firing but only during the remapping elicited by a shift in AO contingency. Neuroinflammation in the Pf abolished these changes in CIN activity and goal-directed control after the shift in contingency. However, both effects were rescued by either the peripheral or the intra-DMS administration of selegiline, a monoamine oxidase B inhibitor that we found also enhances adenosine triphosphatase activity in CINs. These findings suggest a potential treatment for the cognitive deficits associated with neuroinflammation affecting the function of the Pf and related structures.

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http://hdl.handle.net/10453/174450