Involvement of TRPC5 channels, inwardly rectifying K⁺ channels, PLCβ and PIP₂ in vasopressin‐mediated excitation of medial central amygdala neurons

Abstract

Key points Activation of V1a vasopressin receptors facilitates neuronal excitability in the medial nucleus of central amygdala (CeM) V1a receptor activation excites about 80% CeM neurons by opening a cationic conductance and about 20% CeM neurons by suppressing an inwardly rectifying K+ (Kir) channel The cationic conductance activated by V1a receptors is identified as TRPC5 channels PLCβ‐mediated depletion of PIP2 is involved in V1a receptor‐elicited excitation of CeM neurons Intracellular Ca2+ release and PKC are unnecessary for V1a receptor‐mediated excitation of CeM neurons Abstract Arginine vasopressin (AVP) serves as a hormone in the periphery to modulate water homeostasis and a neuromodulator in the brain to regulate a diverse range of functions including anxiety, social behaviour, cognitive activities and nociception. The amygdala is an essential brain region involved in modulating defensive and appetitive behaviours, pain and alcohol use disorders. Whereas activation of V1a receptors in the medial nucleus of the central amygdala (CeM) increases neuronal excitability, the involved ionic and signalling mechanisms have not been determined. We found that activation of V1a receptors in the CeM facilitated neuronal excitability predominantly by opening TRPC5 channels, although AVP excited about one fifth of the CeM neurons via suppressing an inwardly rectifying K+ (Kir) channel. G proteins and phospholipase Cβ (PLCβ) were required for AVP‐elicited excitation of CeM neurons, whereas intracellular Ca2+ release and the activity of protein kinase C were unnecessary. Prevention of the depletion of phosphatidylinositol 4,5‐bisphosphate (PIP2) blocked AVP‐induced excitation of CeM neurons, suggesting that PLCβ‐mediated depletion of PIP2 is involved in AVP‐mediated excitation of CeM neurons. Our results may provide a cellular and molecular mechanism to explain the anxiogenic effects of AVP in the amygdala.

Arginine vasopressin activates serotonergic neurons in the dorsal raphe nucleus during neonatal developmentin vitroandin vivo

“…In addition, AVP is also known to increase the excitability of neurons directly via V 1a receptors as initially shown in neonatal neurons of the facial nucleus in the brainstem (Raggenbass et al, 1991). Recent data also show a direct increase in neuronal excitability by AVP via suppression of K + -channels in the hippocampal formation including subiculum (Lei et al, 2021), CA1 (Hu et al, 2022) and dentate gyrus (Lei et al, 2022) as well as in the medial aspect of the central amygdala (Boyle et al, 2021). V 1a receptors are coupled to Gα q/11 proteins activating phospholipase C β (PLC β ), which hydrolyses phosphatidylinositol 4-5-biphosphate (PIP 2 ) to inositol triphosphate (IP 3 ) and diacylglycerol (DAG).…”

Neuromedin B excites central lateral amygdala neurons and reduces cardiovascular output and fear‐potentiated startle

“…Coronal brain slices (300 μm) were prepared from virgin male and female Sprague‐Dawley (SD) rats (22–38 days old), as described previously (Boyle et al, 2021; Binqi Hu et al, 2020). The number of males and females for each experiment was kept as equal as possible.…”

Potentials of Neuropeptides as Therapeutic Agents for Neurological Diseases

“…In rodent models of pain, heightened pain responses and neuroinflammation occur concurrently with enhanced excitatory synaptic transmission between the nucleus parabrachialis, basolateral nuclei of the amygdala, and the central nuclei of the amygdala (CeA) [ 116 , 117 ]. The release of neuropeptides calcitonin gene-related peptide (CGRP) [ 118 , 119 ], substance P [ 120 ], and vasopressin [ 121 , 122 , 123 ] have been reported to upregulate the excitatory, glutamatergic drive to enhance pain-related plasticity in the CeA. In contrast, neuropeptide S-, somatostatin-, and oxytocin-expressing neurons inhibit these pain-enhancing factors and downregulate nociceptive tone [ 121 , 122 , 124 , 125 ].…”