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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD041002-04
Application #
6773976
Study Section
Special Emphasis Panel (ZRG1-IFCN-2 (01))
Program Officer
Winer, Karen
Project Start
2001-07-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
4
Fiscal Year
2004
Total Cost
$193,050
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Leng, G; Moos, F C; Armstrong, W E (2010) The adaptive brain: Glenn Hatton and the supraoptic nucleus. J Neuroendocrinol 22:318-29
Teruyama, R; Lipschitz, D L; Wang, L et al. (2008) Central blockade of oxytocin receptors during mid-late gestation reduces amplitude of slow afterhyperpolarization in supraoptic oxytocin neurons. Am J Physiol Endocrinol Metab 295:E1167-71
Li, Chunyan; Tripathi, Pradeep K; Armstrong, William E (2007) Differences in spike train variability in rat vasopressin and oxytocin neurons and their relationship to synaptic activity. J Physiol 581:221-40
Armstrong, William E; Hatton, Glenn I (2006) The puzzle of pulsatile oxytocin secretion during lactation: some new pieces. Am J Physiol Regul Integr Comp Physiol 291:R26-8
Lipschitz, D L; Crowley, W R; Armstrong, W E et al. (2005) Neurochemical bases of plasticity in the magnocellular oxytocin system during gestation. Exp Neurol 196:210-23
Armstrong, William E; Rubrum, Adam; Teruyama, Ryoichi et al. (2005) Immunocytochemical localization of small-conductance, calcium-dependent potassium channels in astrocytes of the rat supraoptic nucleus. J Comp Neurol 491:175-85
Teruyama, Ryoichi; Armstrong, William E (2005) Enhancement of calcium-dependent afterpotentials in oxytocin neurons of the rat supraoptic nucleus during lactation. J Physiol 566:505-18
Shevchenko, Talent; Teruyama, Ryoichi; Armstrong, William E (2004) High-threshold, Kv3-like potassium currents in magnocellular neurosecretory neurons and their role in spike repolarization. J Neurophysiol 92:3043-55
Teruyama, R; Armstrong, W E (2002) Changes in the active membrane properties of rat supraoptic neurones during pregnancy and lactation. J Neuroendocrinol 14:933-44