The long-term objective of this research is to understand the neural mechanisms underlying the release of oxytocin during lactation. The experiments in the present proposal are aimed specifically at determining how norepinephrine and excitatory amino acids, such as glutamate, affect the electrophysiological characteristics of identified oxytocin neurons in the lactating rat using intracellular current and voltage clamp recordings in the hypothalamo-neurohypophysial explant or in acutely isolated neurons from the lactating rat. The present proposal combines the characterization of the actions of excitatory amino acids and norepinephrine with the identification of the recorded neurons as oxytocinergic or vasopressinergic using immunocytochemical or immunoblotting techniques. The broad hypothesis of this project is that norepinephrine and excitatory amino acids interact to shape the firing behavior of oxytocin neurons during lactation.
The Specific Aims of this project are: 1) to examine the effects of norepinephrine and alpha-1 agonists on the membrane properties of oxytocin neurons in lactating female rats; 2) to characterize the action of excitatory amino acids on oxytocin neurons and in particular to identify whether both AMPA and NMDA receptors are present; and 3) to determine the level at which excitatory amino acids and norepinephrine act synergistically on oxytocin neurons. For each aim the effects on the firing pattern of oxytocin neurons as well as the effects on specific membrane potential characteristics and ion channels will be addressed. In addition, the relevance of any effects to oxytocin release will be tested using transmitter-modulated spike trains to drive the electrical stimulation of hormone release from isolated neural lobes. Oxytocin release is essential to normal lactation in all mammals, yet virtually nothing is known about the specific membrane properties of these neurons during lactation.
