Glutamate Mediates an Excitatory Influence of the Paraventricular Hypothalamic Nucleus on the Dorsal Motor Nucleus of the Vagus

Abstract

Data have shown that the paraventricular nucleus of the hypothalamus (PVN) and the dorsal motor nucleus of the vagus (DMNV) play important roles in the regulation of gastrointestinal function and eating behavior. Anatomical studies have demonstrated direct projections from the PVN to the DMNV and physiological studies showed that the DMNV mediates many of the effects of PVN stimulation and electrical current stimulation of the PVN excites a subset of DMNV neurons. The aim of this study was to characterize the role of glutamate receptors in the excitatory influence of the PVN on gut-related DMNV neurons. Using single-cell recording techniques, we determined the effects of kynurenic acid, 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX), and DL-2-amino-5-phosphonopentanoic acid (DL-AP5) on the increase in firing rate due to electrical current stimulation of the PVN. In initial experiments, we studied 24 DMNV neurons excited by electrical current stimulation of the PVN. Kynurenic acid, a broad-spectrum glutamate receptor antagonist, prevented the PVN effect in 22 neurons and significantly attenuated the effect in the other cells. Nine of these neurons demonstrated an inhibition in firing rate with PVN stimulation after pretreatment with kynurenic acid. In a separate group of 12 neurons, we determined the effects of CNQX (1.2 nmol) injected into the DMNV. This AMPA receptor antagonist completely blocked the excitatory response to PVN stimulation of six DMNV neurons and significantly attenuated the response of the other six DMNV neurons. The addition of 1.2 nmol DL-AP5, a N-methyl-D-aspartate (NMDA) receptor antagonist, further attenuated the response to PVN stimulation in four of the five DMNV neurons that were still excited after CNQX treatment. The fifth neuron demonstrated PVN- induced inhibition of firing rate after treatment with CNQX and DL-AP5. In a separate group of 11 DMNV neurons excited by electrical stimulation of the PVN, DL-AP5 partially attenuated the excitatory responses of only four DMNV neurons and did not block the excitation of any cells. The mean latency (14 neurons tested) from the PVN to the DMNV was 37.71 +/- 2.40 (SE) ms. Monosynaptic action potentials and excitatory postsynaptic potentials were demonstrated in three DMNV neurons by intracellular recording. Our results indicate that glutamate released from PVN neurons projecting to the DMNV excite the gut-related vagal motor neurons by acting predominantly on the AMPA receptor. The NMDA receptor plays only a minor role in the excitatory effect.

The Median Preoptic Nucleus Reciprocally Modulates Activity of Arousal-Related and Sleep-Related Neurons in the Perifornical Lateral Hypothalamus

“…Excesses of either L-glutamate or bicuculline can potentially inactivate instead of stimulate MnPN neurons because of depolarization block. However, significantly higher concentrations of these drugs have been used previously to physiologically activate brain regions (Georges and Aston-Jones, 2001;Zhang and Fogel, 2002;Hanamori, 2003;Puig et al, 2003). The concentration of bicuculline used in our study (0.025 g/l in the perfusion fluid and ϳ10 times less in the tissue) was much lower than reported to produce a depolarization blockage (0.75 g/l) in microinjection experiments (Perier et al, 2002).…”

Excitatory and inhibitory local circuit input to the rat dorsal motor nucleus of the vagus originating from the nucleus tractus solitarius

“…For example, hypocretin-immunoreactive terminals also colocalize glutamate [31], and these peptidergic axons, which originate from somata in the hypothalamus, are abundant in the DMV and NTS [28]. It has also been reported that the hypothalamic paraventricular nucleus sends a glutamatergic projection directly to the DMV, the fibers of which likely traverse the NTS [37]. Central amygdala inputs to the vagal complex that are somatostatin-immunoreactive have also been reported to contain GABA [24].…”

Glutamate-induced Calcium Transients in Rat Neurons of the Dorsal Motor Nucleus of the Vagus

“…26 Similarly, stimulation of the paraventricular nucleus of the hypothalamus caused a depolarization of DMNV neurons, which was blocked by AMPA receptor inhibition. 27 A majority of neurons from the dorsal vagal complex that were activated by gastric balloon distention or intraduodenal infusion of either glucose or linolenic acid expressed AMPA and NMDA receptors. 22 Vago-vagal reflexes initiated by gastrointestinal distention have been shown to be mediated by glutamate; this response is attenuated by selective antagonism of AMPA, but not NMDA, receptors.…”