TRANSIENT SYNAPTIC POTENTIATION IN THE VISUAL-CORTEX .1. CELLULAR MECHANISMS

The cellular mechanisms that underlie transient synaptic potentiation were studied in visual cortical slices of adult guinea pigs (greater t han or equal to age 5 wk postnatal). Postsynaptic potentials (PSPs) el icited by stimulation of the white matter/layer VI border were recorde d with conventional intracellular techniques from layer II/III neurons . Transient potentiation (average duration 23 +/- 3 min, mean +/- SE) was evoked by 60 low-frequency (0.1 Hz) pairings of weak afferent stim ulation with coincident intracellular depolarizing pulses (80 ms) of t he postsynaptic cell. Fifty-one percent (47 of 92) of the pairing prot ocols led to significant enhancement (+26 +/- 3%) of the PSP peak ampl itude. Blockade of action potential output from the recorded neuron du ring pairing with Lidocaine, N-ethyl bromide quaternary salt in the re cording micropipette did not reduce the likelihood of potentiation (7 of 14 protocols = 50%). Thus transient synaptic potentiation does not require action potential output from the paired cell or recurrent syna ptic activation in the local cortical circuit. Rather, the modificatio n occurs at synaptic sites that directly impinge onto the activated ne uron. Intracellular postsynaptic blockade of inhibitory PSPs only onto the paired cell with the chloride channel blocker 4,4'-dinitro-stilbe ne-2,2'-disulfonic acid and the potassium channel blocker cesium in th e micropipette also did not reduce the likelihood of induction of pote ntiation (6 of 9 protocols = 67%). These results suggest that the pote ntiation is due to a true upregulation of excitatory synaptic transmis sion and that it does not require a reduction of inhibitory components of the compound PSP for induction. Chelation of postsynaptic intracel lular calcium with 1,2-bis-2-aminophenoxy ethane-N,N,N',N'-tetraacetic acid (BAPTA) in all cases effectively blocked the induction of potent iation (no change in the PSP, 9 of 13 protocols; induction of synaptic depression, 4 of 13 protocols), suggesting that a rise in the intrace llular postsynaptic calcium level is critical for the pairing-induced synaptic potentiation to occur. Bath application of the N-methyl-D-asp artate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV ) reversibly blocked potentiation of the PSP peak amplitude in most ce lls (14 of 16) that were capable of significant potentiation in contro l solution. Blockade of nitric oxide production with bath application of the competitive inhibitor of nitric oxide synthase, L-nitro-arginin e (LNA), did not significantly affect the likelihood of synaptic poten tiation (11 of 20 cells). It did, however, block subsequent enhancemen t for several cells (2 of 4) that had previously had their inputs pote ntiated. Moreover, LNA increased the overall average magnitude of syna ptic potentiation (with an additional +28%) when induction was success ful. These results suggest that endogenous cortical nitric oxide produ ction can both positively and negatively modulate this NMDA receptor-m ediated type of synaptic plasticity.