Chemogenetic silencing of neurons in retrosplenial cortex disrupts sensory preconditioning

Title:
Chemogenetic silencing of neurons in retrosplenial cortex disrupts sensory preconditioning
Authors:
Robinson, Siobhan; Todd, Travis P.; Pasternak, Anna R.; Luikart, Bryan W.; Skelton, Patrick D.; Urban, Daniel G.; Bucci, David J.
Abstract:
An essential aspect of episodic memory is the formation of associations between neutral sensory cues in the environment. In light of recent evidence that this critical aspect of learning does not require the hippocampus, we tested the involvement of the retrosplenial cortex (RSC) in this process using a chemogenetic approach that allowed us to temporarily silence neurons along the entire rostrocaudal extent of the RSC. A viral vector containing the gene for a synthetic inhibitory G-protein-coupled receptor (hM4Di) was infused into RSC. When the receptor was later activated by systemic injection of clozapine-N-oxide, neural activity in RSC was transiently silenced (confirmed using a patch-clamp procedure). Rats expressing hM4Di and control rats were trained in a sensory preconditioning procedure in which a tone and light were paired on some trials and a white noise stimulus was presented alone on the other trials during the Preconditioning phase. Thus, rats were given the opportunity to form an association between a tone and a light in the absence of reinforcement. Later, the light was paired with food. During the test phase when the auditory cues were presented alone, controls exhibited more conditioned responding during presentation of the tone compared with the white noise reflecting the prior formation of a tone-light association. Silencing RSC neurons during the Preconditioning phase prevented the formation of an association between the tone and light and eliminated the sensory preconditioning effect. These findings indicate that RSC may contribute to episodic memory formation by linking essential sensory stimuli during learning.
Citation:
Robinson S., T.P. Todd, A.R. Pasternak, B.W. Luikart, P.D. Skelton, D.G. Urban, and D.J. Bucci. August 2014. "Chemogenetic silencing of neurons in retrosplenial cortex disrupts sensory preconditioning." Journal of Neuroscience 34(33): 10982-10988.
Publisher:
Society for Neuroscience
DATE ISSUED:
2014-08
Department:
Neuroscience
Type:
Article
PUBLISHED VERSION:
10.1523/JNEUROSCI.1349-14.2014
PERMANENT LINK:
http://hdl.handle.net/11282/566810

Full metadata record

DC FieldValue Language
dc.contributor.authorRobinson, Siobhanen
dc.contributor.authorTodd, Travis P.en
dc.contributor.authorPasternak, Anna R.en
dc.contributor.authorLuikart, Bryan W.en
dc.contributor.authorSkelton, Patrick D.en
dc.contributor.authorUrban, Daniel G.en
dc.contributor.authorBucci, David J.en
dc.date.accessioned2015-08-13T10:34:38Zen
dc.date.available2015-08-13T10:34:38Zen
dc.date.issued2014-08en
dc.identifier.citationRobinson S., T.P. Todd, A.R. Pasternak, B.W. Luikart, P.D. Skelton, D.G. Urban, and D.J. Bucci. August 2014. "Chemogenetic silencing of neurons in retrosplenial cortex disrupts sensory preconditioning." Journal of Neuroscience 34(33): 10982-10988.en
dc.identifier.issn0270-6474en
dc.identifier.urihttp://hdl.handle.net/11282/566810en
dc.description.abstractAn essential aspect of episodic memory is the formation of associations between neutral sensory cues in the environment. In light of recent evidence that this critical aspect of learning does not require the hippocampus, we tested the involvement of the retrosplenial cortex (RSC) in this process using a chemogenetic approach that allowed us to temporarily silence neurons along the entire rostrocaudal extent of the RSC. A viral vector containing the gene for a synthetic inhibitory G-protein-coupled receptor (hM4Di) was infused into RSC. When the receptor was later activated by systemic injection of clozapine-N-oxide, neural activity in RSC was transiently silenced (confirmed using a patch-clamp procedure). Rats expressing hM4Di and control rats were trained in a sensory preconditioning procedure in which a tone and light were paired on some trials and a white noise stimulus was presented alone on the other trials during the Preconditioning phase. Thus, rats were given the opportunity to form an association between a tone and a light in the absence of reinforcement. Later, the light was paired with food. During the test phase when the auditory cues were presented alone, controls exhibited more conditioned responding during presentation of the tone compared with the white noise reflecting the prior formation of a tone-light association. Silencing RSC neurons during the Preconditioning phase prevented the formation of an association between the tone and light and eliminated the sensory preconditioning effect. These findings indicate that RSC may contribute to episodic memory formation by linking essential sensory stimuli during learning.en
dc.language.isoen_USen
dc.publisherSociety for Neuroscienceen
dc.identifier.doi10.1523/JNEUROSCI.1349-14.2014en
dc.subject.departmentNeuroscienceen
dc.titleChemogenetic silencing of neurons in retrosplenial cortex disrupts sensory preconditioningen
dc.typeArticleen
dc.identifier.journalJournal of Neuroscienceen
dc.subject.keywordDREADDen
dc.subject.keywordEpisodicen
dc.subject.keywordHippocampusen
dc.subject.keywordParahippocampalen
dc.subject.keywordRetrosplenialen
dc.identifier.volume34en
dc.identifier.issue33en
dc.identifier.startpage10982en
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