STRESS ALLOSTASIS: CRF, SEROTONIN AND THE BNST

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In 2007 we completed our study demonstrating that multiple 5HT receptors are expressed in distinct subpopulations of BNST neurons. Not only do we have physiologic data showing that individual BNST neurons can express more than one receptor, in 2007 we also developed a technique (single cell RT-PCR) whereby we can extract the mRNA from individual neurons and examine their genetic 5HT receptor profile. We also completed our examination of the intrinsic membrane currents that are expressed by individual BNST neurons. We identified at least three distinct cell types in the BNST (Types I - III). In current-clamp mode, these three subtypes show characteristic action potential firing patterns in response to depolarizing current injection, as well as showing a distinct voltage response to hyperpolarizing current injection. The current clamp data suggested that the three subtypes of BNST neuron could be further differentiated based on their expression patterns for specific intrinsic membrane currents. We also began examination of the genetic underpinning for the ion channels that shape the firing pattern of BNST neurons. We employed the same single cell RT-PCR technique to examine the ion channel subunits that are expressed in BNST neurons. To date we have characterized at least 5 IA channel subunits, 3 IT channel subunits and 2 IH channel subunits. Each of these subunits has a different kinetic profile and conductance, as well as a differential distribution within the cell. Hence, the combination of these different ion channel subunits can subtly, but dramatically, influence the firing pattern of these neurons.