Abstract
The possibility that changes in inhibitory processes are responsible for long-term potentiation (LTP) was examined using the rat hippocampal slice preparation. Inhibitory pathways were characterized using both extra- and intracellular recordings from the CA1 pyramidal cell layer. Stimulating electrodes were placed in either stratum radiatum or the alveus to allow orthodromic or antidromic activation of the pyramidal cells. Using extracellular recordings, inhibition was studied by applying paired pulses at interstimulus intervals of 20-500 ms through either the same or different stimulating electrodes, and quantifying the reduction in the population spike. An antidromic conditioning pulse was least effective in influencing the test response, while paired stimuli delivered through separate stimulators in stratum radiatum revealed the longest duration effects. Inhibition was either reduced or enhanced, depending on the stimulation paradigm, with increasing stimulus intensity. With LTP, alterations in paired-pulse inhibition were observed corresponding to the changes in conditioning pulse amplitude. Reducing stimulus intensity to restore the initial conditioning pulse amplitude eliminated these effects. Using intracellular recordings, the effects of LTP on inhibition were studied by examining changes in EPSP[excitatory postsynaptic potential]-IPSP [inhibitory postsynaptic potential] sequences, IPSP evoked by antidromic stimulation, and spontaneous depolarizing IPSP observed with KCl-filled electrodes. Following LTP enhanced EPSP and slightly reduced but prolonged IPSP were observed in response to orthodromic stimulation. Antidromically evoked as well as spontaneous IPSP were unaffected. Alterations in inhibitory processes are not responsible for LTP in hippocampal subfield CA1. Changes in the strength of inhibitory synapses as a consequence of long-term potentiation may modify the functional character of the hippocampal connections.