Optogenetic perturbation of projections from thalamic nucleus reuniens to hippocampus disrupts spatial working memory retrieval more than encoding.
Hippocampus
Memory encoding
Memory retrieval
Spatial working memory
Thalamic nucleus reuniens
Y-maze
Journal
Neurobiology of learning and memory
ISSN: 1095-9564
Titre abrégé: Neurobiol Learn Mem
Pays: United States
ID NLM: 9508166
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
14
10
2020
revised:
08
01
2021
accepted:
20
01
2021
pubmed:
2
2
2021
medline:
30
11
2021
entrez:
1
2
2021
Statut:
ppublish
Résumé
Working memory deficits are key cognitive symptoms of schizophrenia. Elevated delta oscillations, which are uniquely associated with the presence of the illness, may be the proximal cause of these deficits. Spatial working memory (SWM) is impaired by elevated delta oscillations projecting from thalamic nucleus reuniens (RE) to the hippocampus (HPC); these findings imply a role of the RE-HPC circuit in working memory deficits in schizophrenia, but questions remain as to whether the affected process is the encoding of working memory, recall, or both. Here, we answered this question by optogenetically inducing delta oscillations in the HPC terminals of RE axons in mice during either the encoding or retrieval phase (or both) of an SWM task. We transduced cells in RE to express channelrhodopsin-2 through bilateral injection of adeno-associated virus, and bilaterally implanted optical fibers dorsal to the hippocampus (HPC). While mice performed a spatial memory task on a Y-maze, the RE-HPC projections were optogenetically stimulated at delta frequency during distinct phases of the task. Full-trial stimulation successfully impaired SWM performance, replicating the results of the previous study in a mouse model. Task-phase-specific stimulation significantly impaired performance during retrieval but not encoding. Our results indicate that perturbations in the RE-HPC circuit specifically impair the retrieval phase of working memory. This finding supports the hypothesis that abnormal delta frequency bursting in the thalamus could have a causal role in producing the WM deficits seen in schizophrenia.
Sections du résumé
BACKGROUND
Working memory deficits are key cognitive symptoms of schizophrenia. Elevated delta oscillations, which are uniquely associated with the presence of the illness, may be the proximal cause of these deficits. Spatial working memory (SWM) is impaired by elevated delta oscillations projecting from thalamic nucleus reuniens (RE) to the hippocampus (HPC); these findings imply a role of the RE-HPC circuit in working memory deficits in schizophrenia, but questions remain as to whether the affected process is the encoding of working memory, recall, or both. Here, we answered this question by optogenetically inducing delta oscillations in the HPC terminals of RE axons in mice during either the encoding or retrieval phase (or both) of an SWM task.
METHODS
We transduced cells in RE to express channelrhodopsin-2 through bilateral injection of adeno-associated virus, and bilaterally implanted optical fibers dorsal to the hippocampus (HPC). While mice performed a spatial memory task on a Y-maze, the RE-HPC projections were optogenetically stimulated at delta frequency during distinct phases of the task.
RESULTS
Full-trial stimulation successfully impaired SWM performance, replicating the results of the previous study in a mouse model. Task-phase-specific stimulation significantly impaired performance during retrieval but not encoding.
CONCLUSIONS
Our results indicate that perturbations in the RE-HPC circuit specifically impair the retrieval phase of working memory. This finding supports the hypothesis that abnormal delta frequency bursting in the thalamus could have a causal role in producing the WM deficits seen in schizophrenia.
Identifiants
pubmed: 33524571
pii: S1074-7427(21)00018-6
doi: 10.1016/j.nlm.2021.107396
pmc: PMC7987745
mid: NIHMS1668119
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107396Subventions
Organisme : NIMH NIH HHS
ID : R01 MH110391
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS104818
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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