A Thalamo-Hypothalamic Pathway That Activates Oxytocin Neurons in Social Contexts in Female Rats

Abstract

Oxytocin is released from neurons in the paraventricular hypothalamic nucleus (PVN) in mothers upon suckling and during adult social interactions. However, neuronal pathways that activate oxytocin neurons in social contexts are not yet established. Neurons in the posterior intralaminar complex of the thalamus (PIL), which contain tuberoinfundibular peptide 39 (TIP39) and are activated by pup exposure in lactating mothers, provide a candidate projection. Innervation of oxytocin neurons by TIP39 neurons was examined by double labeling in combination with electron microscopy and retrograde tract-tracing. Potential classic neurotransmitters in TIP39 neurons were investigated by in situ hybridization histochemistry. Neurons activated after encounter with a familiar conspecific female in a familiar environment were mapped with the c-Fos technique. PVN and the supraoptic nucleus oxytocin neurons were closely apposed by an average of 2.0 and 0.4 TIP39 terminals, respectively. Asymmetric (presumed excitatory) synapses were found between TIP39 terminals and cell bodies of oxytocin neurons. In lactating rats, PIL TIP39 neurons were retrogradely labeled from the PVN. TIP39 neurons expressed vesicular glutamate transporter 2 but not glutamic acid decarboxylase 67. PIL contained a markedly increased number of c-Fos-positive neurons in response to social encounter with a familiar conspecific female. Furthermore, the PIL received ascending input from the spinal cord and the inferior colliculus. Thus, TIP39 neurons in the PIL may receive sensory input in response to social interactions and project to the PVN to innervate and excite oxytocin neurons, suggesting that the PIL-PVN projection contributes to the activation of oxytocin neurons in social contexts.

Whole brain wiring diagram of oxytocin system in adult mice

“…Notably, PVH OT neurons are strongly connected with the thalamic brain area, which communicates with the cortex and is a key structure for the rapid integration of new learning, working memory, and adaptive decision-making (25), while the SO receives more input from the striatum-like amygdala, which is centered on emotion-based cognitive function (26). This input pattern is overall in agreement with prior reports that utilize traditional retrograde tracers or viral tools (10,30). The anterior two-thirds of the PVH is known to contain the majority of magnocellular neuroendocrine neurons, while the posterior one-third of the PVH contains the descending preautonomic neurons (8).…”

Thalamic integration of social stimuli regulating parental behavior and the oxytocin system

“…This area can be well-characterized neurochemically by the presence and distribution of the calcium binding protein, calbindin (Fig. 1), which is present in all parts of the PIL, essentially delineating its boundaries (Cservenak et al, 2017a). The complexity of the structure is further enhanced by the subdivision of the parvocellular subparafascicular nucleus into a medial and a lateral subdivision defined topographically by the presence of galanin fibers and calcitonin gene-related peptide (CGRP)-containing cell bodies, respectively (Coolen et al, 2003).…”

Neonatal Oxytocin Treatment Ameliorates Autistic-Like Behaviors and Oxytocin Deficiency in Valproic Acid-Induced Rat Model of Autism

“…Substantial evidence indicates that the neuropeptide oxytocin (OXT) is a powerful regulator of social behaviors ( Stoop, 2012 ; Caldwell, 2017 ; Cservenak et al, 2017 ; Yoshihara et al, 2017 ). Oxytocin in the brain is synthesized and secreted by the paraventricular nucleus (PVN) and supraoptic nucleus (SON) ( Stoop, 2012 ), and OXT-containing neural projections and OXT receptors (Oxtr) are widely distributed in the brain areas involved in regulating social behavior ( Caldwell, 2017 ; Song and Albers, 2017 ).…”