Afferent and efferent connections of C1 cells with spinal cord or hypothalamic projections in mice

Abstract

The axonal projections and synaptic input of the C1 adrenergic neurons of the rostral ventrolateral medulla, (VLM) were examined using transgenic dopamine-beta hydroxylase (DβH) Cre mice and modified rabies virus. Cre-dependent viral vectors expressing TVA (receptor for envelopeA) and rabies glycoprotein were injected into the left VLM. EnvelopeA-pseudotyped rabies-EGFP glycoprotein-deficient virus (rabies-EGFP) was injected 4–6 weeks later in either thoracic spinal cord (SC) or hypothalamus. TVA immunoreactivity was detected almost exclusively (95%) in VLM C1 neurons. In mice with SC injections of rabies-EGFP, starter cells (expressing TVA + EGFP) were found at the rostral end of the VLM; in mice with hypothalamic injections starter C1 cells were located more caudally. C1 neurons innervating SC or hypothalamus had other terminal fields in common (e.g., dorsal vagal complex, locus coeruleus, raphe pallidus and periaqueductal gray matter). Putative inputs to C1 cells with SC or hypothalamic projections originated from the same brain regions, especially the lower brainstem reticular core from spinomedullary border to rostral pons. Putative input neurons to C1 cells were also observed in the nucleus of the solitary tract, caudal VLM, caudal spinal trigeminal nucleus, cerebellum, periaqueductal gray matter and inferior and superior colliculi. In sum, regardless of whether they innervate SC or hypothalamus, VLM C1 neurons receive input from the same general brain regions. One interpretation is that many types of somatic or internal stimuli recruit these neurons en bloc to produce a stereotyped acute stress response with sympathetic, parasympathetic, vigilance and neuroendocrine components.

On the presence and functional significance of sympathetic premotor neurons with collateralized spinal axons in the rat

“…; Stornetta et al . ). Peaks in forelimb SNA had response latencies between 125–211 ms, whereas hindlimb SNA peaked at 195–288 ms.…”

Neurochemistry of neurons in the ventrolateral medulla activated by hypotension: Are the same neurons activated by glucoprivation?

“…Similarly reciprocity of projections may influence the activation of neurons, for example, orexin neurons and paraventricular neurons both receive input from C1 neurons but also project to them (Bochorishvili et al, 2014;Geerling, Shin, Chimenti, & Loewy, 2010;Korim et al, 2016;Li, Wang, Elsarelli, Brown, & Ritter, 2015). Furthermore whether or not the same neurons are activated by different transmitters released from the same terminal under different stimulus conditions remains unknown as does whether collateral pathways arising from C1 neurons (Bochorishvili et al, 2014;Card et al, 2006;McMullan & Pilowsky, 2012;Stornetta et al, 2016) are equally activated by different stimuli. With respect to the specific stimuli used here it could be useful to determine whether barodenervation alters the cellular responses to 2DG.…”

C1 neurons: a nodal point for stress?

“…Most (perhaps all) C1 neurons, including those that innervate the spinal cord, also innervate supraspinal nuclei (Haselton & Guyenet, ; Stornetta et al . ). Notably, bulbospinal and hypothalamus‐projecting C1 cells innervate a common set of structures, including the locus coeruleus, the dorsolateral pons and the periaqueductal grey matter (Fig.…”