Role of Connexin 36 in Autoregulation of Oxytocin Neuronal Activity in Rat Supraoptic Nucleus

Abstract

In the supraoptic nucleus (SON), the incidence of dye coupling among oxytocin (OT) neurons increases significantly in nursing mothers. However, the type(s) of connexin (Cx) involved is(are) unknown. In this study, we specifically investigated whether Cx36 plays a functional role in the coupling between OT neurons in the SON of lactating rats. In this brain region, Cx36 was mainly coimmunostained with vasopressin neurons in virgin female rats, whereas in lactating rats, Cx36 was primarily colocalized with OT neurons. In brain slices from lactating rats, application of quinine (0.1 mM), a selective blocker of Cx36, significantly reduced dye coupling among OT neurons as well as the discharge/firing frequency of spikes/action potentials and their amplitude, and transiently depolarized the membrane potential of OT neurons in whole-cell patch-clamp recordings. However, quinine significantly reduced the amplitude, but not frequency, of inhibitory postsynaptic currents in OT neurons; the duration of excitatory postsynaptic currents was reduced but not their frequency and amplitude. Furthermore, the excitatory effect of OT (1 pM) on OT neurons was significantly weakened and delayed by quinine, and burst firing was absent in the presence of this inhibitor. Lastly, Western blotting analysis revealed that the presence of combined, but not alone, quinine and OT significantly reduced the amount of Cx36 in the SON. Thus, Cx36-mediated junctional communication plays a crucial role in autoregulatory control of OT neuronal activity, likely by acting at the postsynaptic sites. The level of Cx36 is modulated by its own activity and the presence of OT.

Astrocytic Hydrogen Sulfide Regulates Supraoptic Cellular Activity in the Adaptive Response of Lactating Rats to Chronic Social Stress

“…During lactation, suckling can elicit astrocytic morphological plasticity (Wang & Hatton, 2009b) and other neurochemical events including intrahypothalamic OT release (Neumann et al, 1993;Li et al, 2021b), patterned synaptic input (Wang & Hatton, 2004;Popescu et al, 2019), intercellular gap junctional coupling (Wang et al, 2019a), OTR-associated signaling events (Hatton & Wang, 2008), and activation of some ion channels (Li et al, 2020c(Li et al, , 2021a. Among them, astrocytic plasticity plays an essential role as evidenced in previous (Wang & Hatton, 2009b;Wang et al, 2017) and the present observations.…”

Involvement of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 3 in Oxytocin Neuronal Activity in Lactating Rats With Pup Deprivation

“…Two methods were used for coimmunoprecipitation experiments. For assaying molecular association between molecules in lactation rats, the protocol was the same as previously described (Wang et al., 2019). Briefly, total tissue lysates of the SON were precleared with protein A/G agarose beads (sc-2003, RRID:AB_10201400) to reduce nonspecific binding.…”

“…The pulsatility of oxytocin secretion relies on the maturation of hypothalamic machinery for the milk-ejection reflex around parturition and on the ability of oxytocin neurons to discharge burst of action potentials in synchrony during lactation ( Russell et al., 2001 ; Hatton and Wang, 2008 ; Hou et al., 2016 ). The burst synchrony depends on coordinative activities of neurochemical environment, particularly increase in somatodendritic oxytocin secretion in the hypothalamus ( Neumann et al., 1993 ), oxytocin receptor (OTR)-associated signaling events ( Hatton and Wang, 2008 ), intercellular junctional coupling ( Wang et al., 2019 ), and astrocytic plasticity ( Wang and Hatton, 2009b ). Among these factors, OTR has been identified on oxytocin neurons and their adjacent astrocytes in the SON ( Wang and Hatton, 2006 ).…”

Cell-Adhesion Properties of β-Subunits in the Regulation of Cardiomyocyte Sodium Channels

“…It is likely that there are other biological situations where the necessary conditions for ephaptic conduction apply. Potential examples include the repetitive firing that occur in neuroendocrine supraoptic nucleus neurones [ 121 , 122 ] and the escape reflex triggered by activation of the goldfish Mauthner neurone [ 123 ]. Interestingly, the R85H mutation in the β1 Ig domain, that compromises ephaptic conduction between cardiomyocytes [ 66 ] ( Section 2.1 , Figure 7 B), also predisposes to epilepsy [ 124 ], perhaps hinting at a similar role in neurones.…”