NMDA Receptor-dependent Transient Homo- and Heterosynaptic Depression in Picrotoxin-treated Hippocampal Slices.
Extracellular recording was used to study the effects of high-frequency (tetanic) stimulation on excitatory synaptic transmission in the CA1 region of rat hippocampal slices in the presence of the gamma-aminobutyric acid (GABA) type A antagonist, picrotoxin (50 microM). Under these conditions tetanic stimulation (100 Hz, 1 s) at the test intensity resulted in homosynaptic long-term potentiation (LTP). In contrast, tetanic stimulation of higher intensity (100 Hz, 1 s, double test intensity) resulted in homo- and heterosynaptic depression which recovered within 45 min. A transient (1 - 3 min) negative shift in DC potential and a transient (5 - 10 min) depression of the homosynaptic fibre volley occurred immediately following the higher intensity tetanus. The DC shift, induction of homo- and heterosynaptic depression and depression of the fibre volley were reversibly prevented by the N-methyl-d-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonopentanoate (AP5; 20 microM) but were not prevented by a variety of L-type calcium channel antagonists. Transient (30 - 45 min) synaptic depression of pharmacologically isolated NMDA receptor-mediated field excitatory postsynaptic potentials also occurred following tetanic stimulation (100 Hz, 1 s) at double test intensity. These results demonstrate an NMDA receptor-dependent form of reversible synaptic depression in the CA1 region of the hippocampus.
Bashir
Zafar I.
ZI
Department of Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK, and Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Collingridge
Graham L.
GL