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HIV‐1 inhibits long‐term potentiation and attenuates spatial learning
Author(s) -
Li ShengTian,
Matsushita Masayuki,
Moriwaki Akiyoshi,
Saheki Yasunori,
Lu YunFei,
Tomizawa Kazuhito,
Wu HaiYan,
Terada Hiroaki,
Matsui Hideki
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10844
Subject(s) - long term potentiation , nmda receptor , neuroscience , hippocampal formation , hippocampus , facilitation , biology , human immunodeficiency virus (hiv) , receptor , psychology , immunology , biochemistry
Although memory deficits have been clearly documented in patients with human immunodeficiency virus type‐1 (HIV‐1) infection, the physiological basis of this dysfunction is poorly understood. We focused on Tat, a viral protein released from HIV‐1–infected cells and investigated its effect on spatial learning in adult mice. An intracerebroventricular injection of Tat leads to attenuation of spatial learning accompanied by suppression of long‐term potentiation (LTP), the cellular basis of spatial learning, in hippocampal cornu ammonis 1 pyramidal neurons. Tat facilitates extrasynaptic but not synaptic N ‐methyl‐ D ‐aspartate (NMDA) receptor activity. Taken together, these data provide strong evidence that the Tat pathway underlies the development of memory dysfunction in patients with HIV‐1 infection and suggest a causal relationship between Tat, the facilitation of extrasynaptic NMDA receptor activity, inhibition of LTP, and attenuation of spatial learning.