Glutamatergic transmission in the nucleus tractus solitarii: from server to peripherals in the cardiovascular information superhighway

Abstract

Afferent nerves carrying signals from mechanoreceptors in the aortic arch and carotid sinus terminate predominantly in the nucleus tractus solitarii (NTS). Signal transduction and neurotransmission in the NTS are critical for central cardiovascular reflect control, but little was known about either until the late 1970's. None of the numerous neuroactive chemicals found in the NTS had met strict criteria as a neurotransmitter in the baroreflex arc until data suggested that the excitatory amino acid L-glutamate (GLU) might be released from baroreceptor afferent terminals in the NTS. In anesthetized animals microinjection into the NTS of GLU, which can be demonstrated in terminals in the NTS, produces cardiovascular responses like those seen with activation of the baroreceptor reflex. Similar responses occur in awake animals if the chemoreceptor reflex is eliminated; otherwise, in conscious animals responses mimic those of chemoreceptor reflect activation. GLU released in the NTS upon selective activation of the baroreceptor, and possibly the chemoreceptor, reflex. Responses to selective agonists as well as baroreflex responses are eliminated by GLU antagonists microinjected into the NTS. Non-NMDA (N-methyl-D-aspartic acid) receptors seem to predominate at primary baroreceptor synapses in the NTS while NMDA receptors may be involved at later synapses. Although inhibition of soluble guanylate cyclase attenuates responses to ionotropic glutamate agonists in the NTS, nitric oxide does not seem to play a role in glutamate transmission in the NTS. GLU may also participate in transmission at cardiovascular neurons beyond the NTS. For example, a role has been suggested for GLU in the ventrolateral medulla and spinal cord. Work continues concerning GLU signal transduction and mechanisms that modulate that transduction both at the NTS and at other cardiovascular nuclei.

Glutamate receptor subunits in the nucleus of the tractus solitarius and other regions of the medulla oblongata in the cat

“…This idea is supported to some extent by physiological studies. Talman (1997) noted that non-NMDA (i.e., AMPA/kainate receptors) predominate at primary baroreceptor synapses in the NTS. Zhang and Mifflin (1997), who studied baroreceptor afferent input to the NTS of the rat, found that functionally different populations of neurons apparently possess different combinations of NMDA versus AMPA/kainate receptors.…”

5-Hydroxytryptamine–Mediated Neurotransmission Modulates Spontaneous and Vagal-Evoked Glutamate Release in the Nucleus of the Solitary Tract Effect of Uptake Blockade

“…The nucleus tractus solitarius (NTS), located near the dorsal surface of the brainstem, is known to be important in the integration of this visceral sensory information (Andresen and Kunze, 1994). Glutamate is considered the major transmitter mediating cardiovascular and visceral afferent input to the NTS (Talman, 1997;Baude et al, 2009). However, along with some other transmitters, 5-hydroxytryptamine (5-HT; serotonin) has also been implicated in visceral afferent neurotransmission (see Ramage and Villalón, 2008).…”

Colocalization of neurokinin-1, N-methyl-d-aspartate, and AMPA receptors on neurons of the rat nucleus tractus solitarii

“…Of the numerous neurotransmitters found in the NTS, glutamate is the principal excitatory neurotransmitter and has been recognized to play a pivotal role in regulating cardiovascular functions in the NTS (Seagard et al, 2001;Talman et al, 1980;Talman, 1997). Studies have also suggested that substance P (SP), acting at neurokinin-1 (NK1) receptors (Feldman, 1995;Zhang et al, 2000), plays a role in neuromodulation of cardiovascular control in the NTS (Boscan et al, 2002;Gillis et al, 1980;Potts, 2006), though a role for the peptide in transmission of baroreflex signals has been controversial.…”