Hdl Handle:
http://hdl.handle.net/10675.2/833
Title:
Evidence for a Developmental Role for TLR4 in Learning and Memory
Authors:
Okun, Eitan; Barak, Boaz; Saada-Madar, Ravit; Rothman, Sarah M.; Griffioen, Kathleen J.; Roberts, Nicholas; Castro, Kamilah; Mughal, Mohamed R.; Pita, Mario A.; Stranahan, Alexis M.; Arumugam, Thiruma V.; Mattson, Mark P.
Abstract:
Toll-like receptors (TLRs) play essential roles in innate immunity and increasing evidence indicates that these receptors are expressed in neurons, astrocytes and microglia in the brain where they mediate responses to infection, stress and injury. Very little is known about the roles of TLRs in cognition. To test the hypothesis that TLR4 has a role in hippocampus-dependent spatial learning and memory, we used mice deficient for TLR4 and mice receiving chronic TLR4 antagonist infusion to the lateral ventricles in the brain. We found that developmental TLR4 deficiency enhances spatial reference memory acquisition and memory retention, impairs contextual fear-learning and enhances motor functions, traits that were correlated with CREB up-regulation in the hippocampus. TLR4 antagonist infusion into the cerebral ventricles of adult mice did not affect cognitive behavior, but instead affected anxiety responses. Our findings indicate a developmental role for TLR4 in shaping spatial reference memory, and fear learning and memory. Moreover, we show that central TLR4 inhibition using a TLR4 antagonist has no discernible physiological role in regulating spatial and contextual hippocampus-dependent cognitive behavior.
Citation:
PLoS One. 2012 Oct 11; 7(10):e47522
Issue Date:
11-Oct-2012
URI:
http://hdl.handle.net/10675.2/833
DOI:
10.1371/journal.pone.0047522
PubMed ID:
23071817
PubMed Central ID:
PMC3469493
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Physiology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorOkun, Eitanen_US
dc.contributor.authorBarak, Boazen_US
dc.contributor.authorSaada-Madar, Raviten_US
dc.contributor.authorRothman, Sarah M.en_US
dc.contributor.authorGriffioen, Kathleen J.en_US
dc.contributor.authorRoberts, Nicholasen_US
dc.contributor.authorCastro, Kamilahen_US
dc.contributor.authorMughal, Mohamed R.en_US
dc.contributor.authorPita, Mario A.en_US
dc.contributor.authorStranahan, Alexis M.en_US
dc.contributor.authorArumugam, Thiruma V.en_US
dc.contributor.authorMattson, Mark P.en_US
dc.date.accessioned2012-10-26T20:35:13Z-
dc.date.available2012-10-26T20:35:13Z-
dc.date.issued2012-10-11en_US
dc.identifier.citationPLoS One. 2012 Oct 11; 7(10):e47522en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid23071817en_US
dc.identifier.doi10.1371/journal.pone.0047522en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/833-
dc.description.abstractToll-like receptors (TLRs) play essential roles in innate immunity and increasing evidence indicates that these receptors are expressed in neurons, astrocytes and microglia in the brain where they mediate responses to infection, stress and injury. Very little is known about the roles of TLRs in cognition. To test the hypothesis that TLR4 has a role in hippocampus-dependent spatial learning and memory, we used mice deficient for TLR4 and mice receiving chronic TLR4 antagonist infusion to the lateral ventricles in the brain. We found that developmental TLR4 deficiency enhances spatial reference memory acquisition and memory retention, impairs contextual fear-learning and enhances motor functions, traits that were correlated with CREB up-regulation in the hippocampus. TLR4 antagonist infusion into the cerebral ventricles of adult mice did not affect cognitive behavior, but instead affected anxiety responses. Our findings indicate a developmental role for TLR4 in shaping spatial reference memory, and fear learning and memory. Moreover, we show that central TLR4 inhibition using a TLR4 antagonist has no discernible physiological role in regulating spatial and contextual hippocampus-dependent cognitive behavior.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectNeurological Systemen_US
dc.subjectMotor Systemsen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMouseen_US
dc.subjectNeuroscienceen_US
dc.subjectCognitive Neuroscienceen_US
dc.subjectCognitionen_US
dc.subjectMotor Reactionsen_US
dc.subjectAnimal Cognitionen_US
dc.subjectBehavioral Neuroscienceen_US
dc.subjectLearning and Memoryen_US
dc.titleEvidence for a Developmental Role for TLR4 in Learning and Memoryen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3469493en_US
dc.contributor.corporatenameDepartment of Physiology-

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