Sensory afferent and hypoxia-mediated activation of nucleus tractus solitarius neurons that project to the rostral ventrolateral medulla

Abstract

The nucleus tractus solitarius (nTS) of the brainstem receives sensory afferent inputs, processes that information, and sends projections to a variety of brain regions responsible for influencing autonomic and respiratory output. The nTS sends direct projections to the rostral ventrolateral medulla (RVLM), an area important for cardiorespiratory reflexes and homeostasis. Since the net reflex effect of nTS processing ultimately depends on the properties of output neurons, we determined the characteristics of these RVLM-projecting nTS neurons using electrophysiological and immunohistochemical techniques. RVLM-projecting nTS neurons were identified by retrograde tracers. Patch clamp analysis in the horizontal brainstem nTS slice demonstrated that RVLM-projecting nTS cells exhibit constant latency solitary tract evoked EPSCs, suggesting they receive strong monosynaptic contacts from visceral afferents. Three distinct patterns of action potential firing, associated with different underlying potassium currents, were observed in RVLM-projecting cells. Following activation of the chemoreflex in conscious animals by three hours of acute hypoxia, 11.2 ± 1.9% of the RVLM-projecting nTS neurons were activated, as indicated by positive Fos-immunoreactivity. Very few RVLM-projecting nTS cells were catecholaminergic. Taken together, these data suggest that RVLM projecting nTS neurons receive strong monosynaptic inputs from sensory afferents and a subpopulation participates in the chemoreflex pathway.

Systemic administration of leptin potentiates the response of neurons in the nucleus of the solitary tract to chemoreceptor activation in the rat

“…Injections of tract tracers into the RVLM have been shown to retrogradely label neurons within subnuclei of the caudal NTS consistent with the location of where single units were recorded in this study (Ross et al, 1985;Otake et al, 1992;Otake et al, 1993;Hardie et al, 1996;Kline, 2010). In addition, Kline et al (2010) have reported that neurons within the caudal NTS retrogradely labeled from the RVLM are activated by hypoxia, as indicated by expression of the nuclear phosphoprotein fos. Similarly, an earlier electrophysiological study has reported that neurons within the Com subnuclei of NTS were antidromically activated by stimulation of RVLM pressor sites (Koshiya and Guyenet, 1996).…”

Synaptic transmission of baro- and chemoreceptors afferents in the NTS second order neurons

“…In spite of this possibility, several previous studies about NTS neurons and neurotransmission of autonomic reflexes suggested that other afferent inputs, such as the peripheral chemoreceptors afferents, also presented a low SD of latency in NTS 2nd-order neurons, similar to baroreceptors afferents (Kline et al, 2007(Kline et al, , 2010Zhang and Mifflin, 2007;Andresen and Peters, 2008).…”

Catecholaminergic neurons projecting to the paraventricular nucleus of the hypothalamus are essential for cardiorespiratory adjustments to hypoxia

“…TH terminals in the PVN were evaluated in a subset of IgG-(n ϭ 4) and DSAP-treated (n ϭ 3) rats. TH, the rate-limiting enzyme in catecholamine synthesis, was used as a marker in classifying neurons as catecholaminergic (28,45). Immunohistochemistry was performed simultaneously on tissue from IgG-and DSAP-treated rats.…”

“…Peripheral chemoreceptor afferent nerves from the carotid bodies project onto neurons located in the nucleus tractus solitarii (nTS) (40, 51), where chemoreceptor afferent input is modulated and integrated. The nTS sends projections to the rostral ventrolateral medulla (RVLM) (28,30), and this projection is considered the primary pathway mediating cardiorespiratory chemoreflex responses.The hypothalamic paraventricular nucleus (PVN) is also important in the integrated response to chemoreflex activation. PVN neurons are activated by peripheral and central chemoreflex stimulation, including hypoxia and hypercapnia (3,11,22).…”

“…Peripheral chemoreceptor afferent nerves from the carotid bodies project onto neurons located in the nucleus tractus solitarii (nTS) (40, 51), where chemoreceptor afferent input is modulated and integrated. The nTS sends projections to the rostral ventrolateral medulla (RVLM) (28,30), and this projection is considered the primary pathway mediating cardiorespiratory chemoreflex responses.…”