Central blockade of oxytocin receptors during mid-late gestation reduces amplitude of slow afterhyperpolarization in supraoptic oxytocin neurons

Abstract

The neurohypophysial hormone oxytocin (OT), synthesized in magnocellular paraventricular (PVN) and supraoptic (SON) nuclei, is well known for its effects in lactation. Our previous studies showed that central OT receptor (OTR) binding is increased during gestation and that blockade of central OTRs, specifically during mid-late gestation, causes a delay in OT release during suckling and reduces weight gain in pups, suggesting decreased milk delivery. In the present study, we tested whether central OTR blockade during late gestation disrupts the gestation-related plasticity in intrinsic membrane properties. Whole cell current-clamp recordings were performed in OT neurons from pregnant rats (19 -22 days in gestation) that were infused with an OTR antagonist (OTA) or artificial cerebrospinal fluid (aCSF) and from virgin rats infused with aCSF into the third ventricle via an osmotic minipump beginning on days 12-14 of gestation. The amplitudes of both Ca 2ϩ -dependent afterhyperpolarizations (AHPs), an apamin-sensitive medium AHP (mAHP) and an apamin-insensitive slow AHP (sAHP), were significantly increased during late gestation in control pregnant animals. However, the amplitude of the sAHP from pregnant rats treated with the OTA was significantly smaller than that of pregnant control rats and similar to that of virgins. These results indicate that the diminished efficiency in lactation due to OTR blockade may be partly a result of an altered sAHP that would shape OT bursting. These findings suggest that central actions of OT during late gestation are necessary for programming the plasticity of at least some of the intrinsic membrane properties in OT neurons during lactation.vasopressin; electrophysiology; hypothalamus; lactation; hyperpolarizing afterpotentials THE NEUROHYPOPHYSIAL HORMONES oxytocin (OT) and vasopressin (VP) are synthesized in the magnocellular cells (MNCs) located in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei. These hormones are released into the systemic circulation from the neurohypophysis in response to physiological demands, such as milk ejection and parturition for OT (14, 30) and osmotic and cardiovascular challenge for VP (31). The release of OT is determined by the rate and pattern of neuronal activity of SON and PVN neurons (31). During lactation, OT neurons display a short (2-4 s), highfrequency (up to 80 Hz) burst of action potentials shortly before each milk ejection. This bursting activity is synchronized among all OT neurons (4) and results in a bolus release of OT into the bloodstream. This pulsatile OT release into the general circulation is believed to maximize the biological effects of OT (6) and is requisite for milk ejection (17,33,36).The firing patterns of MNCs are critically modulated by intrinsic membrane properties, such as the Ca 2ϩ -dependent afterhyperpolarizations (AHPs) and the Ca 2ϩ -dependent depolarizing afterpotentials (DAPs). Both AHPs and DAPs are specifically enhanced during lactation (37-39), indicating that these changes interact with ...

Central Nervous System Control of Oxytocin Secretion during Lactation

“…219 The increase in AHPs observed by Stern and Armstrong 301 and Teruyama and Armstrong 303,304 involves two types of potentials following spike trains, one of medium duration (mAHP) (tau 100-200 m) and a slow AHP (tau 1.5-2 s) (sAHP). Both AHPs appear to first enlarge during late pregnancy, 304,306 suggesting that suckling is not the triggering stimulus. This increase was not accompanied by an increase in intracellular Ca ++ during spike trains, or in whole cell Ca ++ current under voltage clamp.…”

“…311 In addition, E2 is known to upregulate OTRs. Teruyama et al 306 investigated the role of central OT in AHP plasticity. 313 The steroid replacement model was used by Montagnese et al 314 to determine the factors involved in the morphological plasticity of the OT system known to occur in lactation, well documented for over 30 years.…”

Chronic Hyperosmotic Stress Converts GABAergic Inhibition into Excitation in Vasopressin and Oxytocin Neurons in the Rat

“…The oxytocin receptor antagonist was infused (2.4 g/d) (Teruyama et al, 2008) for 10 d while the rats were exposed to the high Na ϩ drinking water. The vehicle (i.e., ACSF) infusion served as the control.…”

Biocytin-labelling and its impact on late 20th century studies of cortical circuitry

“…The biocytin-labeling method was easily adapted to whole cell recordings from slices using lower pipette-concentrations of biocytin ( e.g., Kawaguchi, 1992), and for the Armstrong lab, this latter method continues to allow a much more detailed characterization of many membrane, synaptic and calcium-handling properties in identified vasopressin and oxytocin neurons (Stern et al , 1999; Shevchenko et al , 2004; Roper et al , 2003; 2004; Teruyama and Armstrong, 2007) as well as the plasticity of oxytocin neurones during pregnancy and lactation (Stern et al , 2000; Teruyama, Armstrong, 2005; 2007; 2008). …”