Neurons In Medulla Research Articles

CARDIOVASCULAR EFFECTS AFTER GLUTAMATE MICROINJECTION INTO THE RVLM OF MSG OBESE CONSCIOUS RATS

Obesity is a precursor condition of several diseases, among them hypertension. The sympathoexcitatory neurons of the rostral ventrolateral medulla (RVLM), which directly innervate sympathetic preganglionic neurons in the intermediolateral cell columns of the spinal cord, are a possible target for cardiovascular modulation by obesity, and glutamatergic neurotransmission has an important role. Thus, the aim of this study was to determine the effect of glutamate microinjection into the RVLM in control and MSG obese rats. Obesity was induced by intradermal administration of 4 mg/g of monosodium glutamate (MSG) or hyperosmotic saline (control = CTR) in the first 5 days of life in male Wistar rats. At 90 days old, the animals were submitted to guide cannulae implantation to the RVLM for unilateral microinjection of L‐glutamate (5 nmol/100 nl) in conscious state for recording for mean arterial pressure (MAP) and heart rate (HR). There was no difference in MAP and HR at baseline among the experimental groups (CTR: 112 ± 2 mmHg, 362 ± 14 bpm; MSG: 106 ± 3 mmHg, 389 ± 13 bpm). Unilateral microinjection of l‐glutamate produced an increase in MAP in CTR and MSG groups, however, the magnitude of this response was higher in obese rats (CTR: 44 ± 3; MSG: 56 ± 2, p=0,02). The excitation of the RVLM with glutamate decreased HR to levels that were not statistically different between groups (CTR: −26 ± 19 bpm; MSG: −45 ± 37 bpm). The present results suggest that MSG obese rats may have elevated sympathetic nerve activity originated from the activity of RVLM neurons.

Selective innervation of upper and lower thoracic spinal segments by medullary raphe neurons in felines

The medullary raphe nuclei mediate a variety of physiological responses, including the regulation of blood pressure. We have demonstrated that vestibular stimulation results in distinct changes in blood flow in the upper and lower body, indicating that the nervous system has the capacity to elicit regionally‐specific changes in blood flow. Prior physiological studies have shown that neurons in the rostral ventrolateral medulla (RVLM) are not responsible for this response patterning. In the present study, we ascertained whether neurons in the medullary raphe nuclei have the capacity to independently regulate sympathetic outflow to different body regions. For this purpose, multiple injections of the fluorescent dye Fast Blue were made into the vicinity of the intermediolateral cell column (IML) in T4, whereas multiple injections of Fluoro‐Ruby were made near the IML in T10. Retrogradely labeled neurons were mapped in the medullary raphe nuclei. Neurons that were single‐labeled for each of the dyes and those that were double‐labeled were noted in approximately equal numbers. These findings show that although some medullary raphe neurons regulate sympathetic outflow from multiple spinal segments, others have the capacity to control activity in specific segments.

Collateralizaton of projections of rostral ventrolateral medulla (RVLM) neurons to levels of the thoracic spinal cord that regulate upper‐ and lower‐body blood flow

We have demonstrated that vestibular stimulation results in distinct changes in blood flow in the upper and lower body, indicating that the sympathetic nervous system has the capacity to elicit regionally‐specific changes in blood flow. Since the RVLM plays a major role in regulating blood flow, the present study tested the hypothesis that distinct populations of RVLM neurons project to the T4 segment (which controls blood flow in the upper body) and the T10 segment (which regulates lower body blood flow). For this purpose, multiple injections of the fluorescent dye Fast Blue were made in cats in the vicinity of the intermediolateral cell column (IML) in T4, whereas multiple injections of the dye Fluoro‐Ruby were made near the IML in T10. RVLM neurons that were single‐labeled for one of the tracers (indicating that they projected to only one segment) were approximately four times more prevalent than those that were double‐labeled (had collateralized projections to both T4 and T10), including catecholaminergic neurons identified through immunohistochemistry. A χ2 test confirmed that double‐labeled cells were less prevalent than single‐labeled RVLM neurons (p<0.001). Our conclusion from these data is that the RVLM has the capacity to independently regulate sympathetic nervous system influences on blood flow in different body regions.

In pursuit of scientific excellence: sex matters

the year 2012 marks the 125th anniversary of the American Physiological Society (APS). Throughout its history, APS has been a leader in innovation and excellence in scientific technology, discovery, education, and publication. Consistent with this history, APS is leading the scientific publication

Angiotensin Type 1A Receptors in C1 Neurons of the Rostral Ventrolateral Medulla Modulate the Pressor Response to Aversive Stress

The rise in blood pressure during an acute aversive stress has been suggested to involve activation of angiotensin type 1A receptors (AT(1A)Rs) at various sites within the brain, including the rostral ventrolateral medulla. In this study we examine the involvement of AT(1A)Rs associated with a subclass of sympathetic premotor neurons of the rostral ventrolateral medulla, the C1 neurons. The distribution of putative AT(1A)R-expressing cells was mapped throughout the brains of three transgenic mice with a bacterial artificial chromosome-expressing green fluorescent protein under the control of the AT(1A)R promoter. The overall distribution correlated with that of the AT(1A)Rs mapped by other methods and demonstrated that the majority of C1 neurons express the AT(1A)R. Cre-recombinase expression in C1 neurons of AT(1A)R-floxed mice enabled demonstration that the pressor response to microinjection of angiotensin II into the rostral ventrolateral medulla is dependent upon expression of the AT(1A)R in these neurons. Lentiviral-induced expression of wild-type AT(1A)Rs in C1 neurons of global AT(1A)R knock-out mice, implanted with radiotelemeter devices for recording blood pressure, modulated the pressor response to aversive stress. During prolonged cage-switch stress, expression of AT(1A)Rs in C1 neurons induced a greater sustained pressor response when compared to the control viral-injected group (22 ± 4 mmHg for AT(1A)R vs 10 ± 1 mmHg for GFP; p < 0.001), which was restored toward that of the wild-type group (28 ± 2 mmHg). This study demonstrates that AT(1A)R expression by C1 neurons is essential for the pressor response to angiotensin II and that this pathway plays an important role in the pressor response to aversive stress.

Inspiratory-activated and inspiratory-inhibited airway vagal preganglionic neurons in the ventrolateral medulla of neonatal rat are different in intrinsic electrophysiological properties

This study investigates the firing properties of the inspiratory-activated and inspiratory-inhibited airway vagal preganglionic neurons located in the external formation of the nucleus ambiguus. The results showed that inspiratory-activated and inspiratory-inhibited neurons are distributed with different density and site preference in this area. Inspiratory-inhibited neurons exhibit significantly more positive resting membrane potential, more negative voltage threshold and lower minimal current required to evoke an action potential under current clamp. The afterhyperpolarization in inspiratory-activated neurons was blocked by apamin, a blocker of the small-conductance Ca(2+)-activated K(+) channels; and that in inspiratory-inhibited neurons by charybdotoxin, a blocker of the large-conductance Ca(2+)-activated K(+) channels. Under voltage clamp, depolarizing voltage steps evoked tetrodotoxin-sensitive rapid inward sodium currents, 4-aminopyridine-sensitive outward potassium transients and lasting outward potassium currents. 4-Aminopyridine partially blocked the lasting outward potassium currents of inspiratory-activated neurons but was ineffective on those of inspiratory-inhibited neurons. These findings suggest that inspiratory-activated and inspiratory-inhibited neurons are differentially organized and express different types of voltage-gated ion channels.

Neuronal representation of visual motion and orientation in the fly medulla

In insects, the first extraction of motion and direction clues from local brightness modulations is thought to take place in the medulla. However, whether and how these computations are represented in the medulla stills remain widely unknown, because electrical recording of the neurons in the medulla is difficult. As an effort to overcome this difficulty, we employed local electroporation in vivo in the medulla of the blowfly (Calliphora vicina) to stain small ensembles of neurons with a calcium-sensitive dye. We studied the responses of these neuronal ensembles to spatial and temporal brightness modulations and found selectivity for grating orientation. In contrast, the responses to the two opposite directions of motion of a grating with the same orientation were similar in magnitude, indicating that strong directional selectivity is either not present in the types of neurons covered by our data set, or that direction-selective signals are too closely spaced to be distinguished by our calcium imaging. The calcium responses also showed a bell-shaped dependency on the temporal frequency of drifting gratings, with an optimum higher than that observed in one of the subsequent processing stages, i.e., the lobula plate. Medulla responses were elicited by on- as well as off-stimuli with some spatial heterogeneity in the sensitivity for “on” and “off”, and in the polarity of the responses. Medulla neurons thus show similarities to some established principles of motion and edge detection in the vertebrate visual system.

Brain Angiotensin-II-derived Reactive Oxygen Species: Implications for High Blood Pressure

Hypertension and its relation to free radicals have been matter of continuous research worldwide. This review is based on the premise that some forms of neurogenic hypertension is, in part, caused by the formation of Angiotensin- II (Ang II)-derived reactive oxygen species within the brain, especially in areas along the Subfornical Organ- Paraventricular Nucleus of the Hypothalamus-Rostral Ventrolateral Medulla pathway (SFO-PVN-RVLM pathway). Here we will discuss the recent contribution of our laboratory and others regarding the mechanisms by which neurons in the Rostral Ventrolateral Medulla (RVLM) are activated by Ang II, how they communicate with the SFO and PVN and more importantly, how Ang II-derived Reactive Oxygen Species (ROS) participate along the SFO-PVN-RVLM pathway in the pathogenesis of neurogenic hypertension.

Central Control of Brown Adipose Tissue Thermogenesis

Thermogenesis, the production of heat energy, is an essential component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature and plays a key role in elevating body temperature during the febrile response to infection. Mitochondrial oxidation in brown adipose tissue (BAT) is a significant source of neurally regulated metabolic heat production in many species from mouse to man. BAT thermogenesis is regulated by neural networks in the central nervous system which responds to feedforward afferent signals from cutaneous and core body thermoreceptors and to feedback signals from brain thermosensitive neurons to activate BAT sympathetic nerve activity. This review summarizes the research leading to a model of the feedforward reflex pathway through which environmental cold stimulates BAT thermogenesis and includes the influence on this thermoregulatory network of the pyrogenic mediator, prostaglandin E2, to increase body temperature during fever. The cold thermal afferent circuit from cutaneous thermal receptors, through second-order thermosensory neurons in the dorsal horn of the spinal cord ascends to activate neurons in the lateral parabrachial nucleus which drive GABAergic interneurons in the preoptic area (POA) to inhibit warm-sensitive, inhibitory output neurons of the POA. The resulting disinhibition of BAT thermogenesis-promoting neurons in the dorsomedial hypothalamus activates BAT sympathetic premotor neurons in the rostral ventromedial medulla, including the rostral raphe pallidus, which provide excitatory, and possibly disinhibitory, inputs to spinal sympathetic circuits to drive BAT thermogenesis. Other recently recognized central sites influencing BAT thermogenesis and energy expenditure are also described.

Importance of rostral ventrolateral medulla neurons in determining efferent sympathetic nerve activity and blood pressure

Accentuated sympathetic nerve activity (SNA) is a risk factor for cardiovascular events. In this review, we investigate our working hypothesis that potentiated activity of neurons in the rostral ventrolateral medulla (RVLM) is the primary cause of experimental and essential hypertension. Over the past decade, we have examined how RVLM neurons regulate peripheral SNA, how the sympathetic and renin-angiotensin systems are correlated and how the sympathetic system can be suppressed to prevent cardiovascular events in patients. Based on results of whole-cell patch-clamp studies, we report that angiotensin II (Ang II) potentiated the activity of RVLM neurons, a sympathetic nervous center, whereas Ang II receptor blocker (ARB) reduced RVLM activities. Our optical imaging demonstrated that a longitudinal rostrocaudal column, including the RVLM and the caudal end of ventrolateral medulla, acts as a sympathetic center. By organizing and analyzing these data, we hope to develop therapies for reducing SNA in our patients. Recently, 2-year depressor effects were obtained by a single procedure of renal nerve ablation in patients with essential hypertension. The ablation injured not only the efferent renal sympathetic nerves but also the afferent renal nerves and led to reduced activities of the hypothalamus, RVLM neurons and efferent systemic sympathetic nerves. These clinical results stress the importance of the RVLM neurons in blood pressure regulation. We expect renal nerve ablation to be an effective treatment for congestive heart failure and chronic kidney disease, such as diabetic nephropathy.

Baro-excited neurons in the caudal ventrolateral medulla (CVLM) recorded using the whole-cell patch-clamp technique

Caudal ventrolateral medulla (CVLM) neurons have important roles in the regulation of sympathetic nerve activity and blood pressure through their tonic inhibition of rostral ventrolateral medulla neurons. As few reports have demonstrated CVLM neuronal activity using the whole-cell patch-clamp technique, we attempted to find neurons in the CVLM that are depolarized by the stimulation of baroreceptors. To record the membrane potentials of the neurons in the CVLM, we developed a modified brainstem-spinal cord preparation that enabled us to change the pressure exerted on the aortic arch and carotid sinuses. We were able to identify neurons in the CVLM in which they were depolarized and the action potential (AP) frequency was increased upon baroreceptor stimulation. We referred to these neurons as baro-excited CVLM neurons. When these preparations were superfused with an angiotensin-II (Ang-II) solution, the frequency of the APs increased in 10 of the 14 baro-excited CVLM neurons. Superfusion with a low-Ca(2+), high-Mg(2+) solution abolished the APs in all seven baro-excited CVLM neurons, suggesting that the baro-excited CVLM neurons did not fire spontaneously. When the preparation was superfused with a low-Ca(2+) solution, 6 of the 7 baro-excited CVLM neurons did not respond to Ang-II superfusion. We for the first time found the baro-excited CVLM neurons, which depolarized pressure dependently but may not fire spontaneously. As Ang-II did not change the activity of the CVLM neurons during superfusion with a low-Ca(2+), high-Mg(2+) solution, the presynaptic neurons may be mandatory for the Ang-II-induced activation of postsynaptic baro-excited CVLM neurons.

Neuronal Loss in the Rostral Ventromedial Medulla in a Rat Model of Neuropathic Pain

Cell death has been reported in the CNS in models of neuropathic pain (Sugimoto et al., 1990; Whiteside and Munglani, 2001; Scholz et al., 2005; Fuccio et al., 2009). In our present study, we examined the effects of spinal nerve ligation (SNL) on the number of neurons in the rostral ventromedial medulla (RVM), a brainstem region involved in modulation of nociception. In rats receiving SNL, we found that the number of RVM neurons decreased by 23% in the side ipsilateral to the surgery. The loss of RVM neurons was also associated with a bilateral increase in the number of glia as well as bilateral activation of both astrocytes and microglia. Administration of tauroursodeoxycholic acid (TUDCA), which reportedly inhibits apoptosis, significantly reduced the loss of neurons, the increase in glia, and the mechanical hypersensitivity induced by SNL. Among RVM neurons, we found that serotonergic (5-hydroxytryptamine, 5-HT) neurons decreased by 35% ipsilateral to SNL. Consistent with these findings, the density of 5-HT-immunoreactive varicosities in the superficial dorsal horn of the spinal cord was 15-30% lower, ipsilateral to SNL. To test the function of the remaining 5-HT neurons, we administered the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). Interestingly, after 5,7-DHT, mechanical withdrawal thresholds increased significantly. We conclude that nerve injury induces death of antinociceptive RVM neurons that can be reduced or abolished by TUDCA. We propose that the loss of RVM neurons shifts the balance of descending control from pain inhibition to pain facilitation.

Descending projections from the rostral ventromedial medulla (RVM) to trigeminal and spinal dorsal horns are morphologically and neurochemically distinct

Neurons in the rostral ventromedial medulla (RVM) are thought to modulate nociceptive transmission via projections to spinal and trigeminal dorsal horns. The cellular substrate for this descending modulation has been studied with regard to projections to spinal dorsal horn, but studies of the projections to trigeminal dorsal horn have been less complete. In this study, we combined anterograde tracing from RVM with immunocytochemical detection of the GABAergic synthetic enzyme, GAD67, to determine if the RVM sends inhibitory projections to trigeminal dorsal horn. We also examined the neuronal targets of this projection using immunocytochemical detection of NeuN. Finally, we used electron microscopy to verify cellular targets. We compared projections to both trigeminal and spinal dorsal horns. We found that RVM projections to both trigeminal and spinal dorsal horn were directed to postsynaptic profiles in the dorsal horn, including somata and dendrites, and not to primary afferent terminals. We found that RVM projections to spinal dorsal horn were more likely to contact neuronal somata and were more likely to contain GAD67 than projections from RVM to trigeminal dorsal horn. These findings suggest that RVM neurons send predominantly GABAergic projections to spinal dorsal horn and provide direct input to postsynaptic neurons such as interneurons or ascending projection neurons. The RVM projection to trigeminal dorsal horn is more heavily targeted to dendrites and is only modestly GABAergic in nature. These anatomical features may underlie differences between trigeminal and spinal dorsal horns with regard to the degree of inhibition or facilitation evoked by RVM stimulation.

Differential modulation of neurons in the rostral ventromedial medulla by neurokinin-1 receptors

The rostral ventromedial medulla (RVM) is part of descending circuitry that modulates nociceptive processing at the level of the spinal cord. RVM output can facilitate pain transmission under certain conditions such as inflammation, and thereby contribute to hyperalgesia. Evidence suggests that substance P and activation of neurokinin-1 (NK-1) receptors in the RVM are involved in descending facilitation of nociception. We showed previously that injection of NK-1 receptor antagonists into the RVM attenuated mechanical and heat hyperalgesia produced by intraplantar injection of capsaicin. Furthermore, intraplantar injection of capsaicin excited ON cells in the RVM and inhibited ongoing activity of OFF cells. In the present studies, we therefore examined changes in responses of RVM neurons to mechanical and heat stimuli after intraplantar injection of capsaicin and determined the role of NK-1 receptors by injecting a NK-1 receptor antagonist into the RVM prior to capsaicin. After capsaicin injection, excitatory responses of ON cells and inhibitory responses of OFF cells evoked by mechanical and heat stimuli applied to the injected, but not contralateral, paw were increased. Injection of the NK-1 antagonist L-733,060 did not alter evoked responses of ON or OFF cells but attenuated the capsaicin-evoked enhanced responses of ON cells to mechanical and heat stimuli with less of an effect on the enhanced inhibitory responses of OFF cells. These data support the notion that descending facilitation from RVM contributes to hyperalgesia and that NK-1 receptors, presumably located on ON cells, play an important role in initiating descending facilitation of nociceptive transmission.

A trigeminoreticular pathway: implications in pain.

Neurons in the caudalmost ventrolateral medulla (cmVLM) respond to noxious stimulation. We previously have shown most efferent projections from this locus project to areas implicated either in the processing or modulation of pain. Here we show the cmVLM of the rat receives projections from superficial laminae of the medullary dorsal horn (MDH) and has neurons activated with capsaicin injections into the temporalis muscle. Injections of either biotinylated dextran amine (BDA) into the MDH or fluorogold (FG)/fluorescent microbeads into the cmVLM showed projections from lamina I and II of the MDH to the cmVLM. Morphometric analysis showed the retrogradely-labeled neurons were small (area 88.7 µm2±3.4) and mostly fusiform in shape. Injections (20–50 µl) of 0.5% capsaicin into the temporalis muscle and subsequent immunohistochemistry for c-Fos showed nuclei labeled in the dorsomedial trigeminocervical complex (TCC), the cmVLM, the lateral medulla, and the internal lateral subnucleus of the parabrachial complex (PBil). Additional labeling with c-Fos was seen in the subnucleus interpolaris of the spinal trigeminal nucleus, the rostral ventrolateral medulla, the superior salivatory nucleus, the rostral ventromedial medulla, and the A1, A5, A7 and subcoeruleus catecholamine areas. Injections of FG into the PBil produced robust label in the lateral medulla and cmVLM while injections of BDA into the lateral medulla showed projections to the PBil. Immunohistochemical experiments to antibodies against substance P, the substance P receptor (NK1), calcitonin gene regulating peptide, leucine enkephalin, VRL1 (TPRV2) receptors and neuropeptide Y showed that these peptides/receptors densely stained the cmVLM. We suggest the MDH- cmVLM projection is important for pain from head and neck areas. We offer a potential new pathway for regulating deep pain via the neurons of the TCC, the cmVLM, the lateral medulla, and the PBil and propose these areas compose a trigeminoreticular pathway, possibly the trigeminal homologue of the spinoreticulothalamic pathway.

Vasostatin I (CgA17–76) vasoconstricts rat splanchnic vascular bed but does not affect central cardiovascular function

Vasostatin I (CgA1–76) is a naturally occurring biologically active peptide derived from chromogranin A (CgA), and is so named for its inhibitory effects on vascular tension. CgA mRNA is expressed abundantly in sympathoexcitatory catecholaminergic neurons of the rostral ventrolateral medulla (RVLM). CgA microinjection into the RVLM decreases blood pressure (BP), heart rate (HR) and sympathetic nerve activity (SNA). Proteolytic fragments of CgA are thought to be responsible for the cardiovascular effects observed. We hypothesised that vasostatin I is one of the fragments responsible for the central effects of CgA. We examined the role of a vasostatin I fragment, CgA17–76 (VS-I(CgA17–76)), containing the portion important for biological effects. The effects of VS-I(CgA17–76) delivered by intrathecal injection, or microinjection into the RVLM, on cardio-respiratory function in urethane anaesthetised, vagotomised, mechanically ventilated Sprague-Dawley rats (n=21) were evaluated. The effects of intrathecal VS-I(CgA17–76) on the somato-sympathetic, baroreceptor and peripheral chemoreceptor reflexes were also examined. At the concentrations used (10, 100 or 200μM, intrathecal; or 5μM, RVLM microinjection) VS-I(CgA17–76) produced no change in mean arterial pressure, HR, splanchnic SNA, phrenic nerve amplitude or phrenic nerve frequency. All reflexes examined were unchanged following intrathecal VS-I(CgA17–76). In the periphery, VS-I(CgA17–76) potentiated the contractile effects of noradrenaline on rat mesenteric arteries (n=6), with a significant left-shift in the dose response curve to noradrenaline (3.7×10−7 vs 7.7×10−7). Our results indicate that VS-I(CgA17–76) is active in the periphery but not centrally, and is not a central modulator of cardiorespiratory function and physiological reflexes.

Patterning of somatosympathetic reflexes reveals nonuniform organization of presympathetic drive from C1 and non-C1 RVLM neurons

To determine the organization of presympathetic vasomotor drive by phenotypic populations of rostral ventrolateral medulla (RVLM) neurons, we examined the somatosympathetic reflex (SSR) evoked in four sympathetic nerves together with selective lesions of RVLM presympathetic neurons. Urethane-anesthetized (1.3 g/kg ip), paralyzed, vagotomized and artificially ventilated Sprague-Dawley rats (n = 41) were used. First, we determined the afferent inputs activated by sciatic nerve (SN) stimulation at graded stimulus intensities (50 sweeps at 0.5-1 Hz, 1-80 V). Second, we recorded sympathetic nerve responses (cervical, renal, splanchnic, and lumbar) to intensities of SN stimulation that activated A-fiber afferents (low) or both A- and C-fiber afferents (high). Third, with low-intensity SN stimulation, we examined the cervical SSR following RVLM microinjection of somatostatin, and we determined the splanchnic SSR in rats in which presympathetic C1 neurons were lesioned following intraspinal injections of anti-dopamine-β-hydroxylase-saporin (anti-DβH-SAP). Low-intensity SN stimulation activated A-fiber afferents and evoked biphasic responses in the renal, splanchnic, and lumbar nerves and a single peak in the cervical nerve. Depletion of presympathetic C1 neurons (59 ± 4% tyrosine hydroxylase immunoreactivity profiles lesioned) eliminated peak 2 of the splanchnic SSR and attenuated peak 1, suggesting that only RVLM neurons with fast axonal conduction were spared. RVLM injections of somatostatin abolished the single early peak of cervical SSR confirming that RVLM neurons with fast axonal conduction were inhibited by somatostatin. It is concluded that unmyelinated RVLM presympathetic neurons, presumed to be all C1, innervate splanchnic, renal, and lumbar but not cervical sympathetic outflows, whereas myelinated C1 and non-C1 RVLM neurons innervate all sympathetic outflows examined. These findings suggest that multiple levels of neural control of vasomotor tone exist; myelinated populations may set baseline tone, while unmyelinated neurons may be recruited to provide actions at specific vascular beds in response to distinct stressors.

Increasing intensity of hypoxia augments activation of hypothalamic paraventricular nucleus-projecting neurons in the caudal ventrolateral medulla

Increasing intensity of hypoxia augments activation of hypothalamic paraventricular nucleus-projecting neurons in the caudal ventrolateral medulla

Acute, specific transgenic ‘silencing’ of Phox2b-expressing neurons in the caudal nucleus tractus solitarius reduces arterial pressure and respiration at rest and in response to hypercapnia in conscious rats

The caudal nucleus tractus solitarius (cNTS): 1) receives direct afferent inputs from the peripheral baro- and chemo- receptors; 2) contains neurons directly responsive to CO2 (central chemoreceptors); 3) provides excitatory drive to the neurons in the caudal ventrolateral medulla; 4) is a critical region regulating both baro- and chemo- reflexes, and the set-point of arterial pressure. We hypothesize that transgenic ‘silencing’ of Phox2b-expressing neurons in the cNTS will reduce both respiration and arterial pressure at rest and in response to hypercapnia.

Electrophysiological properties of expiratory and pre-sympathetic neurons in the ventrolateral medulla of rats submitted to chronic intermittent hypoxia

Electrophysiological properties of expiratory and pre-sympathetic neurons in the ventrolateral medulla of rats submitted to chronic intermittent hypoxia