CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory
Miou Zhou,
Stuart Greenhill,
Shan Huang,
Tawnie K Silva,
Yoshitake Sano,
Shumin Wu,
Ying Cai,
Yoshiko Nagaoka,
Megha Sehgal,
Denise J Cai,
Yong-Seok Lee,
Kevin Fox,
Alcino J Silva
Affiliations
Miou Zhou
Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States
Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom; School of Life and Health Sciences, Aston University, Birmingham, United Kingdom
Shan Huang
Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States
Tawnie K Silva
Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States
Yoshitake Sano
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
Shumin Wu
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States
Ying Cai
Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States
Yoshiko Nagaoka
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States
Megha Sehgal
Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States
Denise J Cai
Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States
Yong-Seok Lee
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
Kevin Fox
Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom
Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States
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.
