The interplay between glutamatergic circuits and oxytocin neurons in the hypothalamus and its relevance to neurodevelopmental disorders. (16th November 2021)

• Record Type: Journal Article
• Authors: Leithead, Amanda B.; Tasker, Jeffrey G.; Harony‐Nicolas, Hala
• Is Part Of: Journal of neuroendocrinology. Volume 33:Number 12(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-11-16
• Subjects: glutamate -- hypothalamus -- lactation -- neurodevelopmental disorders -- oxytocin; Neuroendocrinology -- Periodicals; 616.4
• DOI: 10.1111/jne.13061
• Languages: English
• ISSNs: 0953-8194

Abstract

Abstract: Oxytocin (OXT) neurons of the hypothalamus are at the center of several physiological functions, including milk ejection, uterus contraction, and maternal and social behavior. In lactating females, OXT neurons show a pattern of burst firing and inter‐neuron synchronization during suckling that leads to pulsatile release of surges of OXT into the bloodstream to stimulate milk ejection. This pattern of firing and population synchronization may be facilitated in part by hypothalamic glutamatergic circuits, as has been observed in vitro using brain slices obtained from male rats and neonates. However, it remains unknown how hypothalamic glutamatergic circuits influence OXT cell activity outside the context of lactation. In this review, we summarize the in vivo and in vitro studies that describe the synchronized burst firing pattern of OXT neurons and the implication of hypothalamic glutamate in this pattern of firing. We also make note of the few studies that have traced glutamatergic afferents to the hypothalamic paraventricular and supraoptic nuclei. Finally, we discuss the genetic findings implicating several glutamatergic genes in neurodevelopmental disorders, including autism spectrum disorder, thus underscoring the need for future studies to investigate the impact of these mutations on hypothalamic glutamatergic circuits and the OXT system. Abstract : Oxytocin (OXT) neurons of the hypothalamus are involved in several physiological functions, including milk ejection, uterus contraction, and maternal and social behavior. Synchronized, burst firing of oxytocin neurons in the hypothalamus during lactation leads to pulsatile release of oxytocin into the bloodstream to stimulate milk ejection. Glutamate has been shown to influence this pattern of oxytocin neural activity in both in vivo and in vitro models. Extrahypothalamic glutamatergic inputs innervate oxytocin neurons, yet their role in modulating oxytocin neural activity outside the context of lactation is not fully understood and could be of relevance for neurodevelopmental disorders (NDDs), given the recent discoveries of several NDDs‐risk genes encoding for glutamatergic synaptic components. We propose that future studies directed at dissecting the role of glutamatergic circuits in regulating the OXT system and modulating social behaviors will enhance our understanding of the mechanisms of function of the OXT system, and that investigating the impact of NDDs‐associated mutation on the OXT system has the potential to uncover new pathophysiology that could be underlying social behavior deficits.