The long-term goal of my research is to understand how the properties of individual neurons participate within a network to promote associative learning and the normal cognitive processing of information. In both neocortex and hippocampus, 40-100 Hz (gamma) oscillations are observed during specific behaviors. A widely held hypothesis suggests that perception and the binding of features during learning or memory retrieval results from the temporal relationship between coactivated neurons. Gamma oscillations could provide a means for the long-range synchronization of neural activity. Both theoretical and experimental evidence point to inhibitory interneurons as a major source of rhythmogenesis in the hippocampal formation, a region of the brain important for certain aspects of learning and memory. A knowledge of the basic mechanisms underlying interneuron excitability is therefore critical for our understanding their role in hippocampal information processing. There is evidence that unitary synaptic inputs from pyramidal neurons have a high probability of triggering interneuron firing. Active dendritic conductances have been proposed as a mechanism for achieving the observed high firing probability. Specific Aim 1 will test the hypothesis that dendritic spike initiation is a common feature of hippocampal CA3 interneurons. We will first directly test the hypothesis that action potentials are initiated in the dendrites of hippocampal interneurons. Dual patch-clamp recordings from the dendrites and soma of hippocampal CA3 interneurons will be used to determine if spikes originate in the dendrites or in the soma. Next, we will examine whether dendritic spike initiation occurs across specific classes of hippocampal CA3 interneurons. Specific Aim 2 will test the hypothesis that the properties and distribution of voltage-gated conductances favors dendritic spike initiation. Given that differences in voltage-gated Na+ or K+ channels between the soma and dendrites may account for dendritic spike initiation, we will characterize the types of voltage-gated channels found in the dendrites and soma of hippocampal interneurons. Finally, Specific Aim 3 will test the hypothesis that the properties of excitatory synaptic transmission promote a high-firing probability in CA3 interneurons. We will test whether frequency facilitation or the spatial summation of spontaneous synaptic activity enhances the likelihood of interneuron firing in response to minimal excitatory stimulation. The results from this study will further our understanding of how inhibitory interneurons operate within cortical neural networks, including the hippocampal formation.

R01MH060864

2000-01-01

2004-12-31