TRANSGENIC MICE WITH CEREBRAL EXPRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 COAT PROTEIN GP120 SHOW DIVERGENT CHANGES IN SHORT-TERM ANDLONG-TERM POTENTIATION IN CA1 HIPPOCAMPUS

The human immunodeficiency virus type-1 envelope glycoprotein gp120 is shed from the virus and from infected cells and thus can diffuse and interact with a variety of central nervous system cells. Transgenic mi ce constitutively expressing glial fibrillary acidic protein-driven gp 120 from brain astrocytes display neuronal and glial changes resemblin g abnormalities in human immunodeficiency virus type-1-infected human brains.(50) To assess the neurophysiology of these transgenic mice and determine whether gp120 expression impairs synaptic plasticity, we ex amined CA1 population excitatory postsynaptic potentials in hippocampa l slices from transgenic mice and from non-transgenic controls, using a double-blind protocol. Compared with slices from non-transgenic litt ermate controls, slices from gp120 transgenic mice showed four signifi cant alterations: (i) increased mean slopes of normalized population e xcitatory postsynaptic potentials; (ii) larger paired-pulse facilitati on after induction of long-term potentiation at 50 ms interpulse inter vals; (iii) markedly elevated short-term potentiation after 10 and 20 shocks at 100 Hz; and (iv) a significant reduction in the magnitude of CA1 long-term potentiation. In slices from transgenic mice expressing Escherichia coli beta-galactosidase from the same promoter, paired-pu lse facilitation and long-term potentiation were normal. These results indicate that brain slice preparations from gp120 transgenic mice can be used to assess pathophysiological effects of gp120 on neuronal net works. Because short-term potentiation involves presynaptic mechanisms , our results suggest that gp120 expression in these mice enhances eit her presynaptic glutamate release or postsynaptic glutamate receptor f unction, or both. These changes could lead to increased Ca2+ influx, t hereby contributing to neuronal dysfunction and injury. As long-term p otentiation is a cellular model of learning and memory, our results ma y be relevant to memory (cognitive) impairments seen in patients with AIDS. (C) 1998 IBRO. Published by Elsevier Science Ltd.