title: CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory.
abstract: Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV.
authors.affiliation: Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Miou
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom.|School of Life and Health Sciences, Aston University, Birmingham, United Kingdom.
authors.forename: Stuart
authors.identifier: 0000-0002-5038-5258
authors.initials: S
authors.lastname: Greenhill
authors.affiliation: Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Tawnie K
authors.initials: TK
authors.lastname: Silva
authors.affiliation: Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States.|Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan.
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Sano
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Shumin
authors.initials: S
authors.lastname: Wu
authors.affiliation: Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Nagaoka
authors.affiliation: Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Megha
authors.initials: M
authors.lastname: Sehgal
authors.affiliation: Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Cai
authors.affiliation: Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States.|Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Kevin
authors.initials: K
authors.lastname: Fox
authors.affiliation: Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Alcino J
authors.identifier: 0000-0002-1587-4558
authors.initials: AJ
authors.lastname: Silva
mesh_terms: D000200:Action Potentials; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D007858:Learning; D008568:Memory; D051379:Mice; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology; D019713:Receptors, CCR5 / Q000378:metabolism*
chemical_list: C000592874:CCR5 protein, mouse; D019713:Receptors, CCR5
keywords: CCR5; HIV-associated cognitive deficits; barrel cortex; gp120; hippocampus; learning and memory; mouse; neuroscience