Thus far my research efforts have focused on the functional relation between monosynaptic and multisynaptic excitation of the hippocampus by entorhinal afferents. Based on the results of these studies I have proposed a re-conceptualization of the intrinsic circuitry of the hippocampus monosynaptic entorhinal input to CA3 and CA1 provides feedforward modification of activity propagating through the trisynaptic pathway.
The aim of this project is to investigate the cellular mechanisms that underlie observations showing that the nature and extent of the feedforward modification is dynamic, changing as a function of the pattern of entorhinal input. More specifically, I propose to test the hypothesis that synaptic activation of voltage-gated ion channels in CA3 pyramidal dendrites provide a fundamental mechanism by which these neurons integrate signals from multiple subsets of synapses such that occurs with direct, monosynaptic excitation by entorhinal afferents and indirect, disynaptic excitation via the mossy fiber projection. To accomplish this, I will use techniques recently developed in this laboratory including, dendrite- attached patch-clamp recording and high-speed fluorescent imaging.
The specific aims are: l) Characterization of presumed voltage-dependent Ca2+ and Na+ channels in CA3 pyramidal dendrites, evoked by synaptic excitation and/or propagation of action potentials from the soma: 2) Characterization of the functional dynamics of these ion channels when excited by a specific subset of synapses, using different stimulation parameters, including those known to induce short- and long-term change in synaptic strength: and 3) Characterization of the functional dynamics of voltage-activated currents in CA3 dendrites under conditions that mimic physiological activity, such that might occur when multiple subsets of synaptic are excited, or when different patterns of action potentials are evoked in the soma. The possibility that these interactions might underlie the induction and expression of different forms of long-term potentiation (LTP) will also be examined.
