It has long been recognized that a group of neurons in the rostral ventrolateral medulla (RVLM) are an essential component of the central network for maintaining sympathetic vasomotor tone and respiration. Chemical or electrolytic lesions in the RVLM cause a rapid and sustained fall in blood pressure and disruption of respiration in experimental animals. Similar changes in cardio-respiratory dynamics are noted in humans suffering from high cervical cord trauma. To study in depth the electrical behavior and synaptic mechanism of RVLM neurons, an area virtually unexplored, an experimental model consisting of a brainstem- spinal cord preparation isolated from young (25-30 days) rats has now been developed. New preliminary data from our model has shown that a group of neurons in the RVLM are intrinsically active. Whole-cell patch clamp recordings will be made from bulbospinal RVLM neurons identified antidromically by stimulation of the lateral funiculus at the T2 segment or by the presence of the retrograde tracer fluorogold injected into the white matter dorsolateral to the intermediolateral cell column of T2 and T3 segments 3 days prior to experimentation. The following specific aims will be addressed. First, do spinally projecting RVLM neurons exhibit different membrane property and synaptic mechanism as do non-spinally projecting RVLM neurons? Second, do the intrinsically active RVLM neurons possess different membrane currents as do the non-spontaneously active neurons? Third, are the intrinsically active RVLM neurons different from the non-active neurons insofar as their transmitter phenotype is concerned? Lastly, do these two types of RVLM neurons receive different synaptic inputs and/or exhibit different synaptic potentials? A comprehensive study of the electrical behavior and synaptic mechanism that distinguish the activity of intrinsically active from quiescent RVLM neurons constitutes a necessary step toward improving our current knowledge of the neural network which is critical for homeostatic control of blood pressure and respiration. Likewise, their dysfunction may contribute to high blood pressure and other cardio-pulmonary disease states.
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