Plasticity of Oxytocin Neurons During Lactation

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DESCRIPTION (applicant's abstract): Neurosecretory neurons have a large capacity for morphological and physiological plasticity as a function of endocrine state during adulthood. Of principal interest in this project is the formation of new synapses in the supraoptic and paraventricular nuclei of the hypothalamo-neurohypophysial system during lactation, when the demand for oxytocin (OT) release is high. This morphological plasticity is accompanied by significant increases in the activity of glutamate-releasing synapses which are selective for OT neurons, These changes include a doubling in miniature excitatory postsynaptic currents and an increase in the probability of glutamate release. A similar up-regulation has been found for GABAergic synapses. Profound changes in gonadal hormone secretion during late pregnancy are thought to program these changes, anticipating the increased activity of OT neurons. Furthermore, local OT release feeds back on both types of synapse through autoreceptors on OT neurons and/or their presynaptic terminals. Central OT release is critical for the morphological plasticity, and for the normal expression of OT neuronal firing during lactation. In this project, the mechanisms and consequence of this increased synaptic activity will be investigated. There are four Specific Aims: Aim 1) A) To test whether glutamate release at AMPA/Kainate receptors on OT neurons is enhanced during lactation by a change in the presynaptic regulation of its own release; B) To determine whether NMDA receptors participate in this plasticity; Aim 2) To test the combined and differential contribution of GABAergic and glutamatergic activity to spike patterning in OT neurons during lactation; Aim 3) To test whether OT's direct and presynaptic effects on OT neurons are state-dependent, and whether OT can alter the firing pattern of OT neurons during lactation; Aim 4) To test the time-dependence of the increase in glutamatergic activity during pregnancy, and whether it is controlled by gonadal steroid hormones. These studies are important for understanding how the central control of OT neurons adapts to the demands of increased hormone secretion during pregnancy and lactation.