Biomedical subjects

D Mendelowitz

Publications and source records attributed to D Mendelowitz.

At least 19 recordsLinked to original sources

PubMed2005

Hypoxia recruits a respiratory-related excitatory pathway to brainstem premotor cardiac vagal neurons in animals exposed to prenatal nicotine.

The most ubiquitous form of arrhythmia is respiratory sinus arrhythmia in which the heart beat slows during expiration and heart rate increases during inspiration. Whereas respiratory sinus arrhythmia benefits pulmonary gas exchange respiratory dysfunction presents a major challenge to the cardiorespiratory system. Hypoxia evokes a pronounced bradycardia mediated by increases in parasympathetic cardiac activity. It has been hypothesized that the fatal events in sudden infant death syndrome (SIDS) are exaggerated cardiorespiratory responses to hypoxia. This study tests whether premotor cardiac vagal neurons receive rhythmic respiratory-related excitatory synaptic inputs during normoxia and hypoxia, and if animals exposed to nicotine in the prenatal period have exaggerated responses to hypoxia. Premotor cardiac vagal neurons in the nucleus ambiguus were identified in rats by the presence of a fluorescent tracer in medullary slices that generate rhythmic inspiratory-related motor discharge. Respiratory activity was recorded from the hypoglossal nerve and excitatory synaptic events in cardiac vagal neurons were isolated using patch clamp techniques. Adult female rats were implanted with osmotic minipumps that delivered nicotine at a level approximately equivalent to those that occur in moderate to heavy smokers. During normal eupneic respiration, as well as during hypoxia, premotor cardiac vagal neurons from control animals did not receive any rhythmic respiratory-related excitatory inputs. However in animals exposed to nicotine throughout the prenatal period respiratory bursts during hypoxia dramatically increased the frequency of excitatory synaptic events in cardiac vagal neurons. In summary, in animals exposed to nicotine throughout the prenatal period, but not in unexposed animals, respiratory bursts that occur during hypoxia dramatically increase the frequency of excitatory synaptic events in cardiac vagal neurons. This study establishes a likely neurochemical mechanism for the heart rate responses to hypoxia and a link between prenatal nicotine exposure and exaggerated bradycardia responses during hypoxia that may contribute to sudden infant death syndrome.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2004

Action of kappa and Delta opioid agonists on premotor cardiac vagal neurons in the nucleus ambiguus.

Both enkephalin and dynorphin containing fibers are in close proximity to neurons in the nucleus ambiguus, including cardiac vagal neurons. Microinjection of Delta and kappa agonists into the nucleus ambiguus have been shown to evoke decreases in heart rate. Yet little is known about the mechanisms by which Delta and kappa opioid receptors alter the activity of cardiac vagal neurons. This study tests whether kappa and Delta opioid agonists can alter the activity of cardiac vagal neurons by modulating likely opioid targets including voltage gated calcium currents, and both glycinergic and GABA) neurotransmission to cardiac vagal neurons. Cardiac vagal neurons were identified in vitro by a fluorescent tracer and studied using patch clamp techniques. Neither the kappa agonist spiradoline or the Delta agonist [D-Pen(2), D-Pen(5)]enkephalin (DPDPE) modulated the voltage gated calcium currents in cardiac vagal neurons. DPDPE also did not alter either glycinergic or GABAergic synaptic neurotransmission. Spiradoline did not change GABAergic synaptic inputs, but did significantly inhibit glycinergic synaptic inputs to cardiac vagal neurons. At a concentration of 1 microM, spiradoline inhibited the amplitude of glycinergic events, and at a concentration of 5 microM, spiradoline inhibited both glycinergic amplitude and frequency. Spiradoline also inhibited both the amplitude and frequency of glycinergic miniature inhibitory post-synaptic currents, indicating kappa agonists likely act at both presynaptic and postsynaptic sites to inhibit glycinergic neurotransmission to cardiac vagal neurons.

Analgesics, Opioid↗

PubMed2003

Mu-opioid receptors are located postsynaptically and endomorphin-1 inhibits voltage-gated calcium currents in premotor cardiac parasympathetic neurons in the rat nucleus ambiguus.

Activation of opioid receptors in the CNS evokes a dramatic decrease in heart rate which is mediated by increases in inhibitory parasympathetic activity to the heart. Injection of opiates into the nucleus ambiguus, where premotor cardiac parasympathetic nucleus ambiguus neurons are located elicits an increase in parasympathetic cardiac activity and bradycardia. However, the mechanisms responsible for altering the activity of premotor cardiac parasympathetic nucleus ambiguus neurons is unknown. This study examined at the electron microscopic level whether premotor cardiac parasympathetic nucleus ambiguus neurons possess postsynaptic opioid receptors and whether mu-opioid receptor agonists alter voltage-gated calcium currents in these neurons. Premotor cardiac parasympathetic nucleus ambiguus neurons were identified in the rat using retrograde fluorescent tracers. One series of experiments utilized dual-labeling immunocytochemical methods combined with electron microscopic analysis to determine if premotor cardiac parasympathetic nucleus ambiguus neurons contain mu-opioid receptors. In a second series of experiments whole cell patch clamp methodologies were used to determine whether activation of postsynaptic opioid receptors altered voltage-gated calcium currents in premotor cardiac parasympathetic nucleus ambiguus neurons in brainstem slices. The perikarya and 78% of the dendrites of premotor cardiac parasympathetic nucleus ambiguus neurons contain mu-opioid receptors. Voltage-gated calcium currents in premotor cardiac parasympathetic nucleus ambiguus neurons were comprised nearly entirely of omega-agatoxin-sensitive P/Q-type voltage-gated calcium currents. Activation of mu-opioid receptors inhibited these voltage-gated calcium currents and this inhibition was blocked by pretreatment with pertusis toxin. The mu-opioid receptor agonist endomorphin-1, but not the mu-opioid receptor agonist endomorphin-2, inhibited the calcium currents. In summary, mu-opioid receptors are located postsynaptically on premotor cardiac parasympathetic nucleus ambiguus neurons. The mu-opioid receptor agonist endomorphin1 inhibited the omega-agatoxin-sensitive P/Q-type voltage-gated calcium currents in premotor cardiac vagal nucleus ambiguus neurons. This inhibition is mediated via a G-protein mediated pathway which was blocked by pretreatment with pertusis toxin. It is possible that the inhibition of calcium currents may act to indirectly facilitate the activity of premotor cardiac parasympathetic nucleus ambiguus neurons by disinhibition, such as by a reduction in inhibitory calcium activated potassium currents.

Analgesics, Opioid↗

PubMed2002

Arginine vasopressin enhances GABAergic inhibition of cardiac parasympathetic neurons in the nucleus ambiguus.

Previous studies have shown that arginine vasopressin is an important neuropeptide that can modulate the reflex control of blood pressure and heart rate. The nucleus ambiguus, where cardiac parasympathetic neurons are located, receives dense arginine vasopressin projections. However the mechanisms by which arginine vasopressin alters cardiac parasympathetic activity are unknown. We tested the hypothesis that arginine vasopressin can alter the activity of cardiac parasympathetic neurons by altering the spontaneous GABAergic input to these neurons. Experiments were conducted using whole cell patch clamp recordings of cardiac parasympathetic neurons in an in vitro slice preparation in rats. The results of this study demonstrate that arginine vasopressin increases the frequency and amplitude of GABAergic inhibitory post-synaptic currents in cardiac parasympathetic neurons. Arginine vasopressin did not alter the GABAergic currents evoked by exogenous application of GABA. Similarly, in the presence of tetrodotoxin, arginine vasopressin did not alter the frequency, amplitude or decay time of GABAergic miniature synaptic events evoked by high osmolarity. These results indicate that arginine vasopressin likely acts on neurons precedent to cardiac parasympathetic neurons and that arginine vasopressin likely acts not at the synaptic terminal but at the soma or dendrites of the precedent neuron. Oxytocin and agonists for the V(2)-arginine vasopressin and V(1b)-arginine vasopressin receptors had no effect. By contrast, the arginine vasopressin-evoked responses were completely abolished by a selective V(1a)-arginine vasopressin receptor antagonist indicating arginine vasopressin responses are mediated by V(1a)-arginine vasopressin receptors. We conclude that the V(1a)-arginine vasopressin receptor-mediated increase in frequency and amplitude of inhibitory GABAergic activity to cardiac parasympathetic neurons may be at least one mechanism by which central arginine vasopressin may increase heart rate and inhibit reflex bradycardia.

Animals↗

PubMed2002

Endomorphin-2 inhibits GABAergic inputs to cardiac parasympathetic neurons in the nucleus ambiguus.

The nucleus ambiguus is an area containing cardiac vagal neurons, from which originates most of the parasympathetic control regulating heart rate and cardiac function. GABAergic pathways to these neurons have recently been described, yet modulation of this GABAergic input and its impact upon cardiac vagal neurons is unknown. The nucleus ambiguus has been shown to contain mu-opioid receptors and endomorphin-1 and endomorphin-2, the endogenous peptide ligands for the mu-receptor, whilst microinjections of opioids in the ambiguus area evoke bradycardia. The present study therefore examined the effects of endomorphin-1, endomorphin-2 and DAMGO (a synthetic, mu-selective agonist) on spontaneous GABAergic IPSCs in cardiac parasympathetic neurons. Only endomorphin-2 (100 microM) produced a significant inhibition, of both the frequency (-22.8%) and the amplitude (-30.5%) of the spontaneous IPSCs in cardiac vagal neurons. The inhibitory effects of endomorphin-2 were blocked by naloxonazine (10 microM), a selective mu(1) receptor antagonist. Naloxonazine alone (10 microM) had a potentiating effect on the frequency of the GABAergic IPSCs (+161.43%) but not on the amplitude, indicating that GABA release to cardiac vagal neurons may be under tonic control of opioids acting at the mu(1) receptor. Endomorphin-2 did not reduce the responses evoked by exogenous application of GABA. These results indicate that endomorphin-2 acts on mu(1) receptors located on precedent neurons to decrease GABAergic input to cardiac vagal neurons located in the nucleus ambiguus. The subsequent increase in parasympathetic outflow to the heart may be one mechanism by which mu-selective opioids act to induce bradycardia.

Action Potentials↗

PubMed2002

Distribution of mu-opioid receptors in rat visceral premotor neurons.

Agonists of the mu-opioid receptor (MOR) can modulate the activity of visceral premotor neurons, including cardiac premotor neurons. Neurons in brainstem regions containing these premotor neurons also contain dense concentrations of the MOR1. This study examined the distribution of MOR1 within two populations of visceral premotor neurons: one located in the dorsal motor nucleus of the vagus and the other in the nucleus ambiguus. Visceral premotor neurons contained the retrograde tracer Fluoro-Gold following injections of the tracer into the pericardiac region of the thoracic cavity. MOR1 was localized using immunogold detection of an anti-peptide antibody. Visceral premotor neurons in both regions contained MOR1 at somatic and dendritic sites, although smaller dendrites were less likely to contain the receptor than larger dendrites, suggesting there may be selective trafficking of MOR1 within these neurons. MOR1 labeling in nucleus ambiguus neurons was more likely to be localized to plasma membrane sites, suggesting that ambiguus neurons may be more responsive to opioid ligands than neurons in the dorsal motor nucleus of the vagus. In addition, many of the dendrites of visceral premotor neurons were in direct apposition to other dendrites. MOR1 was often detected at these dendro-dendritic appositions that may be gap junctions. Together these findings indicate that the activity of individual visceral premotor neurons, as well as the coupling between neurons, may be regulated by ligands of the MOR.

Animals↗

PubMed2001

Firing properties of identified superior laryngeal neurons in the nucleus ambiguus in the rat.

Superior laryngeal motoneurons control muscles in the larynx and recent work has shown they also have axon collaterals that project to cardiac vagal neurons in the nucleus ambiguus. The present study was undertaken to identify and examine the firing properties of superior laryngeal neurons (SLNs) in the rat. SLNs typically fired spontaneously and repetitively at a rate of 4-7 Hz. The firing was continuous and showed little bursting activity. Firing evoked afterhyperpolarizations were insensitive to apamin but blocked by charybdotoxin. The voltage-gated currents in SLNs consist of a TTX-sensitive Na current and a 4-aminopyridine sensitive K current. It is likely that the activity of these neurons not only control respiratory laryngeal muscles, but may also provide an interaction between the respiratory system and the control of the heart rate.

2-Amino-5-phosphonovalerate↗

PubMed2001

Characteristics of spontaneous and evoked GABAergic synaptic currents in cardiac vagal neurons in rats.

Despite the importance of GABAergic input to cardiac vagal neurons the electrophysiological properties and possible origins of this innervation have not yet been studied. Individual cardiac vagal neurons were identified by a retrograde fluorescent tracer and were studied in an in vitro slice preparation using patch-clamp electrophysiology. Cardiac vagal neurons received spontaneous GABAergic inhibitory post-synaptic currents (IPSCs) that were blocked by the GABA(A) receptor antagonist bicuculline. The spontaneous presynaptic GABAergic input to cardiac vagal neurons in the nucleus ambiguus occurred at a significantly lower frequency than that recorded in cardiac vagal neurons in the dorsal motor nucleus of the vagus. To identify a possible source of the GABAergic innervation to cardiac vagal neurons the nucleus tractus solitarius was electrically stimulated. GABAergic synaptic currents in cardiac vagal neurons, in both the dorsal motor nucleus of the vagus (DMNX) and the nucleus ambiguus (NA), were consistently evoked upon stimulation of the nucleus tractus solitarius and these responses were also blocked by bicuculline.

Animals↗

PubMed2001

Synaptic and neurotransmitter activation of cardiac vagal neurons in the nucleus ambiguus.

Cardiac vagal neurons play a critical role in the control of heart rate and cardiac function. These neurons, which are primarily located in the nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DMNX), dominate the neural control of heart rate under normal conditions. Cardiac vagal activity is diminished and unresponsive in many disease states, while restoration of parasympathetic activity to the heart lessens ischemia and arrhythmias and decreases the risk of sudden death. Recent work has demonstrated that cardiac vagal neurons are intrinsically silent and therefore rely on synaptic input to control their firing. To date, three major synaptic inputs to cardiac vagal neurons have been identified. Stimulation of the nucleus tractus solitarius evokes a glutamatergic pathway that activates both NMDA and non-NMDA glutamatergic postsynaptic currents in cardiac vagal neurons. Acetylcholine excites cardiac vagal neurons via three mechanisms, activating a direct ligand-gated postsynaptic nicotinic receptor, enhancing postsynaptic non-NMDA currents, and presynaptically by facilitating transmitter release. This enhancement by nicotine is dependent upon activation of pre- and postsynaptic P-type voltage-gated calcium channels. Additionally, there is a GABAergic innervation of cardiac vagal neurons. The transsynaptic pseudorabies virus that expresses GFP (PRV-GFP) has been used to identify, for subsequent electrophysiologic study, neurons that project to cardiac vagal neurons. Bartha PRV-GFP-labeled neurons retain their normal electrophysiological properties, and the labeled baroreflex pathways that control heart rate are unaltered by the virus.

Animals↗

PubMed2001

Agatoxin-IVA-sensitive calcium channels mediate the presynaptic and postsynaptic nicotinic activation of cardiac vagal neurons.

Whole cell currents and miniature glutamatergic synaptic events (minis) were recorded in vitro from cardiac vagal neurons in the nucleus ambiguus using the patch-clamp technique. We examined whether voltage-dependent calcium channels were involved in the nicotinic excitation of cardiac vagal neurons. Nicotine evoked an inward current, increase in mini amplitude, and increase in mini frequency in cardiac vagal neurons. These responses were inhibited by the nonselective voltage-dependent calcium channel blocker Cd (100 microM). The P-type voltage-dependent calcium channel blocker agatoxin IVA (100 nM) abolished the nicotine-evoked responses. Nimodipine (2 microM), an antagonist of L-type calcium channels, inhibited the increase in mini amplitude and frequency but did not block the ligand gated inward current. The N- and Q-type voltage-dependent calcium channel antagonists conotoxin GVIA (1 microM) and conotoxin MVIIC (5 microM) had no effect. We conclude that the presynaptic and postsynaptic facilitation of glutamatergic neurotransmission to cardiac vagal neurons by nicotine involves activation of agatoxin-IVA-sensitive and possibly L-type voltage-dependent calcium channels. The postsynaptic inward current elicited by nicotine is dependent on activation of agatoxin-IVA-sensitive voltage-dependent calcium channels.

Animals↗

PubMed2001

Activity of cardiorespiratory networks revealed by transsynaptic virus expressing GFP.

A fluorescent transneuronal marker capable of labeling individual neurons in a central network while maintaining their normal physiology would permit functional studies of neurons within entire networks responsible for complex behaviors such as cardiorespiratory reflexes. The Bartha strain of pseudorabies virus (PRV), an attenuated swine alpha herpesvirus, can be used as a transsynaptic marker of neural circuits. Bartha PRV invades neuronal networks in the CNS through peripherally projecting axons, replicates in these parent neurons, and then travels transsynaptically to continue labeling the second- and higher-order neurons in a time-dependent manner. A Bartha PRV mutant that expresses green fluorescent protein (GFP) was used to visualize and record from neurons that determine the vagal motor outflow to the heart. Here we show that Bartha PRV-GFP-labeled neurons retain their normal electrophysiological properties and that the labeled baroreflex pathways that control heart rate are unaltered by the virus. This novel transynaptic virus permits in vitro studies of identified neurons within functionally defined neuronal systems including networks that mediate cardiovascular and respiratory function and interactions. We also demonstrate superior laryngeal motorneurons fire spontaneously and synapse on cardiac vagal neurons in the nucleus ambiguus. This cardiorespiratory pathway provides a neural basis of respiratory sinus arrhythmias.

Animals↗

PubMed2000

Superior laryngeal neurons directly excite cardiac vagal neurons within the nucleus ambiguus.

The aim of this study was to test whether superior laryngeal neurons have axon collaterals that synapse upon cardiac vagal neurons. Superior laryngeal neurons were tested as likely mediators of cardio-respiratory interaction because these neurons are active in post-inspiration, co-localized with cardiac vagal neurons, and have many axon collaterals within the nucleus ambiguus. Nontoxic fluorescent tracers were utilized to identify, in vitro, both superior laryngeal neurons that innervated the crico-thyroid muscle, and cardiac vagal neurons that projected to cardiac ganglia. Co-localization of these two populations of neurons demonstrated that cardiac vagal and superior laryngeal neurons are both co-localized in the nucleus ambiguus. Simultaneous dual patch clamp recordings were used to either inject depolarizing current and evoke an action potential (current clamp configuration) or control the voltage and depolarize an identified single superior laryngeal neuron (voltage clamp configuration) while simultaneously recording from a cardiac vagal neuron. Depolarization of some, but not all, individual superior laryngeal neurons elicited post-synaptic excitatory currents in cardiac vagal neurons, indicating that at least some superior laryngeal neurons monosynaptically synapse upon cardiac vagal neurons within the nucleus ambiguus.

Animals↗

PubMed1998

Stimulation of NTS activates NMDA and non-NMDA receptors in rat cardiac vagal neurons in the nucleus ambiguus.

While it is widely accepted that tonic and reflex changes in cardiac vagal activity play significant roles in cardiovascular function, little is known about the synaptic pathways in the brainstem responsible for the control of cardiac vagal neurons in the nucleus ambiguus (NA). In this study, we identified the principal post-synaptic receptors activated in cardiac vagal neurons upon stimulation of the nucleus tractus solitarius (NTS). Cardiac vagal neurons were identified by the presence of a retrograde fluorescent tracer and were visualized in rat brainstem slices. Perforated patch clamp techniques were used to record post-synaptic currents. NTS stimulation activated glutamatergic currents in cardiac vagal neurons with a typical delay of 8-18 ms. Post-synaptic responses were separated into NMDA and non-NMDA components using D-2-amino-5-phophonovalerate (AP5) and 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), respectively. In conclusion, this study characterizes a monosynaptic glutamatergic pathway from NTS that activates NMDA and kainate/AMPA post-synaptic receptors in cardiac vagal neurons.

2-Amino-5-phosphonovalerate↗

PubMed1998

Nicotine excites cardiac vagal neurons via three sites of action.

1. Nicotine is involved in many cardio-respiratory diseases, including hypertension and sudden infant death syndrome (SIDS), which is the most common cause of death in infants between 1 month and 1 year of age. While the aetiology of SIDS remains largely unknown, recent clinical studies suggest maternal cigarette smoking is a major risk factor in SIDS and an abnormality of cardio-respiratory control, particularly a centrally mediated slowing of the heart that precedes or accompanies apnoea, is involved. 2. Because the sites, mechanisms of action and diverse receptor types of nicotine within the central nervous system are controversial and poorly understood, in the present study we examined the effects of nicotine on specific brainstem neurons that control heart rate. Cardiac vagal neurons were identified in an in vitro slice preparation using a retrograde fluorescent tracer and were studied using both whole-cell and perforated patch-clamp electrophysiological techniques. 3. We have found there are different pre- and post-synaptic nicotinic receptors that have dramatic effects on glutamatergic neurotransmission as well as directly activating vagal cardio-inhibitory neurons.

Acetylcholine↗

PubMed1996

Voltage-gated currents in identified parasympathetic cardiac neurons in the nucleus ambiguus.

Heart rate is normally dominated by the activity of the cardioinhibitory parasympathetic nervous system, while abnormally low levels of parasympathetic cardiac activity have been implicated in many cardiovascular diseases including hypertension, heart failure and sudden cardiac death. In this study we have examined the voltage-gated currents in parasympathetic cardiac neurons that were identified with a retrograde fluorescent tracer in visualized sections (250 microns) of nucleus ambiguus. Depolarization of parasympathetic cardiac neurons to potentials more positive than -50 mV evoked a rapidly activating and inactivating inward current which could be blocked by tetrodotoxin (TTX), although in some neurons up to 10 microM was required for complete block. The voltage-dependent inactivation properties of this Na current showed relatively broad inactivation characteristics, a characteristic of TTX-resistant Na channels. Depolarization also elicited biphasic outward currents, which were separated into a transient IA type K current using the specific channel antagonist 4-aminopyridine and a long-lasting delayed rectified K current. These voltage-gated Na and K currents define the action potential firing patterns of parasympathetic cardiac neurons, such as frequency adaptation and spike delay, and also determine the activity of these neurons in response to depolarizing and hyperpolarizing synaptic innervation.

4-Aminopyridine↗

PubMed1996

Sensory afferent neurotransmission in caudal nucleus tractus solitarius--common denominators.

The nucleus of the solitary tract (NTS) receives a wide range of sensory inputs including gustatory, gastrointestinal and cardiorespiratory which are loosely segregated viscerotopically to subnuclei. Our laboratory has focused on a dorsomedial area of caudal NTS (mNTS) which is critical for cardiovascular reflexes. Using a brainslice, we study primarily mNTS neurons mono-synaptically activated by solitary tract stimulation. mNTS neurons show varying degrees of delayed excitation, spike frequency adaptation and after hyperpolarizations. Sensory afferent transmission is mediated by glutamate acting at post-synaptic non-NMDA receptors. Glutamate release depends on at least four different presynaptic calcium channels with N-type predominating. This profile of presynaptic calcium channels in NTS is also present at the peripheral soma, but absent from the baroreceptor sensory endings. Many peptides are associated with these sensory neurons and several modulate glutamatergic transmission in mNTS. Angiotensin II facilitates excitatory responses to sensory afferent activation by a presynaptic mechanism. Caudal NTS appears to have a framework of synaptic and cellular mechanisms in common with other NTS areas and peptides may play a critical role modulating this framework.

Animals↗

PubMed1996

Firing properties of identified parasympathetic cardiac neurons in nucleus ambiguus.

This study tests the hypothesis that identified parasympathetic cardiac neurons in the nucleus ambiguus possess pacemaker-like activity or, alternatively, that these neurons are inherently silent. To test this hypothesis and to examine the firing properties of these neurons, parasympathetic cardiac neurons were identified by the presence of a fluorescent tracer previously applied to their terminals surrounding the heart. Perforated patch-clamp electrophysiological techniques were used to study the spontaneous and depolarization-evoked firing patterns of these identified parasympathetic cardiac neurons in an in vitro brain stem slice. Parasympathetic cardiac neurons were silent. On injection of depolarizing current, however, these neurons fired with both little delay and spike frequency adaptation. Hyperpolarizing prepulses elicited a significant delay before depolarization-evoked firing The Ca(2+)-activated K+ channel blocker apamin, but not charybdotoxin, increased the depolarization-activated firing frequency of these neurons and inhibited the afterhyperpolarization. In summary, parasympathetic cardiac neurons do not have pacemaker-like properties, but they do possess discharge characteristics that would enable them to closely follow excitatory synaptic activation for prolonged periods.

Animals↗

PubMed1996

Three types of postsynaptic glutamatergic receptors are activated in DMNX neurons upon stimulation of NTS.

While it is widely accepted that parasympathetic activity plays a significant role in cardiovascular, bronchomotor, and gastrointestinal function, little is known about the synaptic control of parasympathetic vagal neurons. In this study, we identified the neurotransmitter(s) and postsynaptic responses in dorsal motor nucleus of the vagus (DMNX) neurons upon stimulation of the nucleus of the solitary tract (NTS). Neurons were visualized in rat brain stem slices, and perforated patch-clamp techniques were used to record postsynaptic currents. NTS stimulation activated glutamatergic currents in DMNX that were separated into N-methyl-D-aspartate (NMDA) and non-NMDA components using D-2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively. The non-NMDA component was further characterized using cyclothiazide and concanavalin A to block desensitization of DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) and kainate receptors, respectively. Cyclothiazide increased the postsynaptic amplitude, whereas concanavalin A augmented duration, suggesting kainate, but not AMPA, currents are curtailed by desensitization. High frequency stimulations did not alter synaptic efficacy. In conclusion, this study demonstrates the existence of a monosynaptic glutamatergic pathway from NTS that activates NMDA, kainate, and AMPA postsynaptic receptors in DMNX neurons.

2-Amino-5-phosphonovalerate↗