Oxytocin-induced postinhibitory rebound firing facilitates bursting activity in oxytocin neurons

J Neurosci. 2008 Jan 9;28(2):385-94. doi: 10.1523/JNEUROSCI.5198-07.2008.

Abstract

During parturition and lactation, neurosecretory oxytocin (OT) neurons in the hypothalamus achieve pulsatile hormone secretion by coordinated bursts of firing that occur throughout the neuronal population. This activity is partly controlled by somatodendritic release of OT, which facilitates the onset and recurrence of synchronized bursting. To further investigate the cellular mechanisms underlying the control exerted by OT on the activity of its own neurons, we studied the effects of the peptide on membrane potential and synaptic activity in OT neurons in hypothalamic organotypic slice cultures. Bath application of low concentrations of OT (<100 nM) facilitated GABA(A) receptor-mediated inhibitory transmission through a presynaptic mechanism without affecting membrane potential and excitatory glutamatergic synaptic activity. The facilitatory action of OT on GABAergic transmission was dose-dependent, starting at 25 nM and disappearing at concentrations >100 nM. As shown previously, higher concentrations of OT (>500 nM) had the opposite effect, inhibiting GABA(A) receptors via a postsynaptic mechanism. Surprisingly, OT-mediated facilitation of GABAergic transmission promoted action potential firing in 40% of the neurons. Each action potential occurred at the end of the repolarizing phase of an inhibitory potential. Pharmacological dissection revealed that this firing involved the activation of low-threshold activated calcium channels. Detailed statistical analysis showed that OT-mediated firing upregulated bursting activity in OT neurons. It is thus likely to optimize OT secretion and, as a consequence, facilitate delivery and milk ejection in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Action Potentials / drug effects*
  • Animals
  • Dose-Response Relationship, Drug
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • GABA Antagonists / pharmacology
  • Hypothalamus / cytology
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology
  • Inhibitory Postsynaptic Potentials / radiation effects
  • Neural Inhibition / drug effects*
  • Neurons / drug effects*
  • Neurons / metabolism*
  • Nickel / pharmacology
  • Ornipressin / analogs & derivatives
  • Ornipressin / pharmacology
  • Oxytocin / antagonists & inhibitors
  • Oxytocin / metabolism*
  • Oxytocin / pharmacology*
  • Picrotoxin / pharmacology
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Wistar
  • Time Factors
  • Up-Regulation / drug effects
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Pyrimidines
  • vasotocin, desGly(NH2)(9)d(CH2)5-Tyr(Me)(2)-Thr(4)-Orn(8)-
  • Picrotoxin
  • ICI D2788
  • Ornipressin
  • Oxytocin
  • gamma-Aminobutyric Acid
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Nickel