Synapses in the hippocampus display an unusual degree of both short- and long-term changes in efficacy following stimulation. Recent studies suggest that at least some of the long-term changes have a postsynaptic locus. We propose to determine the membrane and synaptic properties of the three major classes of neurons in the hippocampus (CA1, CA3, and dentate neurons), the effects of the putative neuromodulatory agents, serotonin and norepinephrine, on these properties, and the changes that may occur during long-term post-tetanic potentiation of one particular synaptic input. The rationale is that it is necessary first to characterize the membrane and synaptic events exhibited by these neurons before attempting to understand the mechanisms underlying use-dependent changes in synaptic potentials. The preparation will be the in vitro hippocampal slice. Many standard electrophysiological techniques will be utilized, as well as the application to mammalian cortical neurons of voltage-clamp methods. Using these techniques, we will attempt to answer the following questions: (1) What are the passive cable properties of CA1, CA3, and granule cells, and how do they differ between these classes of neurons? (2) Using the intracellular injection of a fluorescent dye, how does the morphology of each neuron relate to its cable properties? (3) What ionic conductances do these neurons process? (4) If Ca ions conductances are present, what role do they play in the behavior of the neuron? (5) Are there direct membrane effects of neuromodulatory agents of hippocampal neurons? (6) Are there postsynaptic changes that produce use-dependent increases in synaptic efficacy, and, if so, what are they?
