Project Summary

Jeffrey Magee, Ph.D. (Independent Investigator 2003) of Louisiana State University, will seek to establish the mechanisms by which neuromodulators (serotonin in particular) control the dendritic procssing of incoming synaptic information. In most CNS neurons, a process termed dendritic integration in which incoming synaptic inputs are widely distributed across dendritic branches and are blended together to generate a coherent output response is the primary cellular-level mechanism of neuronal information processing. In the case of serotonergic input, the activation of 5HT1a and 5HT4 receptor subtypes in hippocampal CA1 pyramidal dendrites alters the activity of several channel types that are important in synaptic integration. Unfortunately, the final impact of this receptor activation on dendritic integration in these cells remains unknown. Dr. Magee’s hypothesis is that dendritic integration/processing varies along with two functional states (one characterized by the theta-rthythm and low input/output levels and another by sharp-waves and much more intense neuronal activity) and would in fact be part of the mechanisms generating them. Of particular importance for this proposal is the idea that in many of the most debilitating psychiatric disorders pyramidal dendrites may not be in a proper modulatory state to produce the appropriate processing mode. Thus, the central hypothesis to be tested is that: serotonin regulates the information processing mode of CA1 pyramidal neurons. We propose to test this by determining the impact of serotonin on the dendritic integration of different spatio-temporal patterns of synaptic input, and furthermore, determine which voltage-gated ion channels are involved and the time course of this modulation.

Program Area: MOOD DISORDERS\Unipolar Depression

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