Asymmetrical changes in lumbar sympathetic nerve activity following stimulation of the sciatic nerve in rat

Korim, Willian Seiji, et al. "Asymmetrical changes in lumbar sympathetic nerve activity following stimulation of the sciatic nerve in rat." Brain research 1391 (2011): 60-70. The somatosympathetic reflex (SSR) can be observed as responses in post ganglionic sympathetic nerves after the stimulation of Type 2 and 3 sensory fibers. Before this study it was known that this reflex produced differential responses in ipsilateral and contralateral hindlimb blood flow (HFB) following activation of the sciatic nerve. However, how these changes were occurring was unknown, Pilowsky's laboratory hypothesized that changes in HBF was due to differential changes in lumbar sympathetic nerve activity (lSNA) and this was being driven by supraspinal structures (RVLM). To do this sciatic nerve stimulation was accomplished while both ipsilateral and contralateral lSNA was recorded under a variety of conditions (normal, cervical spinal transections, and injections of muscimol into the contralateral RVLM). Before the the cervical spinal transections and blockade of the RVLM it was observed that following sciatic nerve stimulation a differential response was observed at the level of the lSNA. Specifically, the ipsilateral recording showed inhibitory potentials corresponding to decreases in lSNA, while contralateral recordings showed sympathoexcitatory potentials corresponding to increased lSNA. This is consistent with previous literature showing increases in ipsilateral HBF and decreases in contralateral HBF following stimulation of type 2 and 3 sensory fibers. The second observation, was following cervical spinal transections both ipsilateral inhibitory and contralateral excitatory response were diminished. This suggests the reflex is controlled partially by a supraspinal structure. Pilowsky hypothesized that the RVLM was taking part in this reflex and initially did microinjections of muscimol into the contralateral RVLM. Following the microinjections all inhibitory and excitatory responses were abolished. To further investigate, microinjections of glutamate antagonist (kynurenic acid) were also injected into the RVLM and it was seen that only the sympathoexcitatory responses were abolished. In conclusion, the microinjections studies suggest that the RVLM plays a role in the sympathoexcitatory SSR by activating pre-ganglionic sympathetic nerves in which then activate the post-ganglionic sympathetic nerves (lSN) controlling blood flow at the level of the hindlimbs. However, the exact role the RVLM plays in sympathoinhibition is still not clear and needs further investigation. ~JI

Intrinsic properties of rostral ventrolateral medulla pre-sympathetic and bulbospinal respiratory neurons of juvenile rats are not affected by chronic intermittent hypoxia.

Exp Physiol. 2014 Apr 11. [Epub ahead of print] Almado CE1, Leao RM, Machado BH. This group has previously shown that rats exposed to chronic intermittent hypoxia (CIH) will exhibit hypertension which correlates with increased sympathetic nerve activity (SNA) during the late expiratory period of breathing. This suggested activation of augmenting expiratory (aug-E) neurons in the RVLM and botzinger complex which project to the phrenic nucleus in the spinal cord. That could either come from changes in cell signaling, or changes in intrinsic cell properties. In this paper they examined the latter of the two possibilities. They used brainstem slices to do patch clamp recordings of the cells in the RVLM and the BotC. To retrogradely label the RVLM cells of interest, they injected a fluorescent tracer in to the T3-T4 IML. To label the RVLM/BotC aug-E cells that project to the phrenic nucleus, they injected rhodamine microbeads into the phrenic nucleus at C4-C5. 4 days later, after recovery, they began the CIH protocol (5 mins normoxia, 4 mins of pure N2 infusion to make 40s of hypoxia at 6% O2, protocol repeated every 9 minutes for 8hr/day, 10 days). The brains of rats were then removed and sectioned so that they could get slices containing the cells they wanted for testing. Cells were identified by fluorescence within the 3 200um slices they could get per brain ALL 18 presympathetic RVLM neurons they found were spontaneously active in slices, and only had a slight reduction in firing frequency after simultaneous blockade of multiple ionotropic receptors, suggesting that the cells have pacemaker activity. When they looked at the properties of these cells after CIH, they found no difference in membrane potential, firing frequency, capacitance, resistance, etc. When they looked at the RVLM/BotC neurons that project to the phrenic nucleus, they looked to be similar to the other cells in terms of cell properties, except that they had a higher input resistance and different, irregular, patern of spontaneous action potential firing. However, they once again found no differences between CIH and control groups. The take home message here is that CIH did NOT alter the intrinsic properties of cells, but that it most likely alters neuromodulation - but they can not say that other cells involved in breathing weren't altered. It would have been neat if they could have maybe drugged the ringer with assorted ionotropic recptor agonists as well as antagonists to see if they would have had differential changes in receptor activity, or if they could have labeled the cells through the patch pipette, fixed the slices, and then done a reconstruction... but I suppose you can only do so much at a time with your experiments. -DH

Increased dietary salt intake enhances the exercise pressor reflex.

Am J Physiol Heart Circ Physiol. 2014 Feb;306(3):H450-4. doi: 10.1152/ajpheart.00813.2013. Yamauchi K, Tsuchimochi H, Stone AJ, Stocker SD, Kaufman MP. People in this group have previously shown that high-salt diets can lead to altered sympathetic signaling in rats, but this time around they wanted to look and see if the diet caused changes in the exercise pressor reflex - which itself depends partly on the RVLM. They fed rats either 0.1% or 4.0% salt diets. Between groups there were no differences in arterial pressure or plasma levels of K, Na, or Cl. However, there was a near significant difference (p=0.06) in heart rate, with the high-salt diet causing a decrease. They then tested the effect of static hindlimb muscle contraction (via tetanic electrical stimulation of motor neurons in the ventral root) on blood pressure and heart rate and saw that rats fed a high-salt diet had enhanced increases in both categories. The increases in both groups were almost completely eliminated by cutting the muscle afferent nerves (L4 and L5 dorsal root denervation), indicating that these afferents are responsible f. To check to see if there was a change in response to sympathetic neural input, they stimulated the lumbar sympathetic chain at different frequencies. This produced frequency-dependent increases in arterial pressure and frequency-dependent decreases in femoral blood flow, and vascular conductance, but there was not a difference between groups. I guess that means that some salt-induced changes happen between the neurons feeding the skeletal muscle and the muscle itself, and that changes they've previously shown in the sympathetic system don't occur at the peripheral sites, but must occur centrally, like in the RVLM. -DH

Peripheral chemoreceptors mediate training-induced plasticity in paraventricular nucleus pre-autonomic oxytocinergic neurons

Josiane C. Cruz, Marina T. Cavalleri, Alexandre Ceroni and Lisete C. Michelini February 1, 2013 Experimental Physiology, 98, 386-396. Previously this laboratory showed that sino-aortic denervation prevented the training induced plasticity. So they investigated the effects of chemoreceptor denervation and on cardiovascular system and on oxytocin gene and protein expression in Paraventricular nucleus (PVN) in SHRs and WKYs that were either sedentary or exercise trained. They measured resting and baroreflex and peripheral chemoreceptor reflex responses. They chemo-denervated rats and assessed treadmill performance along with HR, BP, chemoreceptors responses, baroreceptor responses, along with mRNA and protein expression of oxytocin in PVN. They found that HR was significantly reduced in trained when compared to sedentary rats in SHAM group. However, in the chemo-denervated group the reduced HR response seen in the trained group was not present. Oxytocin mRNA expression in the PVN was upregulated in the sham exercise trained group when compared to the sham sedentary group. In the chemo- denervated rats the oxytocin mRNA was not significantly different between groups. There was increased oxytocin immunoreactivity in the medial and posterior PVN in the sham SHR exercise trained rats when compared to sham SHR sedentary rats. The chemoreceptor reflex is playing an important role in exercise induced changes in PVN oxytocinergic neurons.-MD

Autonomic cardiovascular responses to hypercapnia in conscious rats: the roles of the chemo- and baroreceptors

Shigeru Oikawa, Haruhisa Hirakawa, Tatsumi Kusakabe, Yasuhide Nakashima, Yoshiaki Hayashida Autonomic Neuroscience: Basic and Clinical 117 (2005) 105– 114 The level of CO2 is tightly regulated by the chemoreceptor reflex. We know that this reflex is activated when in response to hypercapnia leading to an increase in blood pressure and sympathetic nerve activity. Heart rate (HR) tends to decrease in response to hypercapnia; however there is evidence to support the opposite effect. This particular study wanted to investigate the role of chemoreceptors and baroreceptors in response to hypercapnia in the conscious rats. Chemo denervation did not have any effect on baroreflex function. They found that in response to hypercapnia there was increases in BP and renal sympathetic nerve activity (RSNA) and a decrease in HR in the intact and chemo denervated rats. Hypercapnia did not affect baroreceptor function in the intact rats. I response to atropine the decrease in HR observed during hypercapnia was not seen. Interestingly, when the aortic depressor nerve was bilateral removed the HR response was not seen. These data demonstrate that the increase in BP and RSNA is due sympatho-exicitatory effect on the central nervous system. Furthermore, the peripheral chemoreceptors are not necessary for activation the sympathetic nervous system. Because after the atropine administration there was no change in HR this shows that there was activation of parasympathetic nervous system. So hypercapnia leads to increases in SNA through central chemoreceptor activation and a decrease in in HR due to activation of the parasympathetic system. Also the chemo-receptors are not playing a major in the cardiovascular response to hypercapnia in conscious but the aortic depressor nerve may play a role in mediating the PSNA response.-MD

Monosynaptic Glutamatergic Activation of Locus Coeruleus and Other Lower Brainstem Noradrenergic Neurons by the C1 Cells in Mice

Holloway, B. B., Stornetta, R. L., Bochorishvili, G., Erisir, A., Viar, K. E., & Guyenet, P. G. (2013). "Monosynaptic Glutamatergic Activation of Locus Coeruleus and Other Lower Brainstem Noradrenergic Neurons by the C1 Cells in Mice." The Journal of Neuroscience, 33(48), 18792-18805. C1 and A1 neuronal cells are within the RVLM which is previously known to be activated by change in stresses and blood pressure. This study utilizes channelrhodopsin-2 (ChR2) and observes the expression of that gene in the brains of adult dopamine-β-hydroxylase (DβH) mice. This can observe the effects of C1 neurons on noradrenergic system. The study showed that ChR2 catecholaminergic cells were VGluT2 and had an excitatory affect on brainstem noradrenergic neurons. C1 and A1 cells did not express GABAergic or glycinergic markers (Comer et al., 1999; Schreihofer et al., 1999; Stornetta and Guyenet, 1999; Stornetta et al., 2002a). This experiment particularly observed the activity of the Locus Coeruleus (LC) neurons based on activation from the C1 neurons. C1 cells relay stimuli to sympathetic preganglionic neurons, LC, A1 and A2 noradrenergic neurons. Basically, the C1 cells are able to excite noradrenergic responses in the CNS. This helped me understand the process of the cascade of mice with dopamine-β-hydroxylase (DβH) which turns dopamine into norepinephrine. This study particularly observed specific C1, LC, and noradrenergic neurons activity. -CW

Losartan improves baroreflex control of heart rate of coarcted hypertensive rats

CLAUDIA M. SANTOS, VERA PONTIERI, MOACIR LEOMIL NETO, AND LISETE C. MICHELINI Am.J.Physiol. 269 (Heart Circ. PhysioZ. 38): H812-H818,1995 They wanted to determine the role of angiotensin II in control of HR and impaired baroreflex control of HR during coarcted hypertension. They measured blood pressure and HR along with assessing plasma renin activity. in sham and coarcted hypertension. They gave losartan and captopril into the lateral ventricle and also gave it orally. They found that losartan given orally and intracerebroventricular helped improved reflex HR responses. However, captopril did have a significant effect on reflex and basal HR. These data suggest that Ang II type 1 receptors in the systemic is playing a role in mediating the control of HR in coarcted hypertension and that antagonism of the rereceptor leads to normalization of HR.-MD

Tyrosine hydroxylase immunoreactivity as indicator of sympathetic activity: simultaneous evaluation in different tissues of hypertensive rats

Katia Burgi,* Marina T. Cavalleri,* Adilson S. Alves, Luiz R. G. Britto, Vagner R. Antunes, and Lisete C. Michelini Am J Physiol Regul Integr Comp Physiol 300: R264–R271, 2011. December 9, 2010; doi:10.1152/ajpregu.00687.2009. Since tyrosine hydroxylase (TH) is a marker of sympathetic nerve activity, they wanted to investigate whether TH would be a good marker for sympathetic innervation to different organ beds. In this article they used tyrosine hydroxylase as an indicator of SNA. THir was then compared to NE content in arterioles by use of high-performance liquid chromatography (HPLC). They also recorded RSNA and LSNA in rats. They did all the recordings and sampling in SHRs and WKYs. They found that in the SHRs that the THir was increased in arterioles taken from heart and kidneys when compared to WKYs. The THir was not different between SHRs and WKYs. They then looked at NE by using HPLC. They found in the SHRs that there was increase NE in the kidney and heart when compared to the WKYs. They also measured RNSA and LSNA in SHRs and WKYs. They found that there were more spiking in the RSNA recording in SHRs when compared to WKYs. They saw no difference between groups for LSNA. This method may be useful for investigating regional difference SNA. -MD

History of Electrophysiological Recording for Functional Neurosurgery, Principles of Extracellular Single-Unit Recording

Microelectrode recording in movement disorder surgery. Zvi Israel, Michael Schulder, Mary M. Heinricher. p1-13 I don’t know if book chapters count for the journal blog, but I’m making a command decision that they do. This is because today I found a couple of chapters in a book about extracellular recording that were pretty great. The first chapter (Zvi Israel and Michael Schulder) was a brief review that covered the history of everything from EEG down to the first intra- and extracellular recording electrodes. The second chapter (Mary M. Heinricher) goes in to the theory of extracellular recordings and detection of field potentials before giving an introduction to the concept of waveform analysis and separation of units in a multi-unit recording by multi-dimensional spike sorting. It wraps up by discussing a few types of sampling biases and how to get around some. This chapter is very basic, but its strength is that it explains the concepts in an incredibly clear way that I’ve never seen in reviews/books before. I’d highly recommend reading at least the second chapter, and I’m hoping I can soon see what’s in later chapters too. -DH

Surgery upregulates high mobility group box-1 and disrupts the blood-brain barrier causing cognitive dysfunction in aged rats.

CNS Neurosci Ther. 2012 Dec;18(12):994-1002. doi: 10.1111/cns.12018. Epub 2012 Oct 19. He HJ, Wang Y, Le Y, Duan KM, Yan XB, Liao Q, Liao Y, Tong JB, Terrando N, Ouyang W. In this paper, suggested by Dr Mueller, the authors looked at how general anesthesia (e.g. isoflurane) can disrupt the blood brain barrier, and lead to expression of HMGB1, a protein involved in regulation of transcription that is believed to be involved in neuroinflamation. To test the idea that anesthesia and surgery cause changes associated with neuroinflamation, rats were anesthetized with isoflurane and some underwent splenectomy. Results: Anesthesia alone did not increase systemic TNF-a or HMGB1, but anesthesia plus surgery did increase MHGB1 on the first postoperative day. When they looked at homogenized hippocampal protein and mRNA of IL-1B, TNF-a, HMGB1, and its receptor, RAGE, all were increased by anesthesia and anesthesia plus surgery. Surgery caused the changes to be significant at 1 and 3 days post-op. They also saw that anesthesia alone was sufficient to cause ruptures to the blood brain barrier, as evidenced by IgG leakage from blood vessels in to parenchyma. This leakage was even worse at 1 and 3 days post-op. In terms of cognition, rats treated with anesthesia or anesthesia and surgery both performed worse than control in a Morris water maze test. So I guess this is something we might want to keep in mind with our rats that get repeatedly imaged for longitudinal MRI studies, and also those who also undergo survival surgery. While this paper didn’t look at changes in the RVLM, it’s reasonable to think that they might occur at the same time the changes are happening in the hippocampus. -DH

Altered Inflammatory Response Is Associated With an Impaired Autonomic Input to the Bone Marrow in the Spontaneously Hypertensive Rat

Zubcevic, Jasenka, et al. "Altered Inflammatory Response Is Associated With an Impaired Autonomic Input to the Bone Marrow in the Spontaneously Hypertensive Rat." Hypertension (2013): HYPERTENSIONAHA-113. This study was interested in the relationship between the immune system and cardiovascular disease, which they examined through the comparison of spontaneous hypertensive rats (SHR) and wild type Wistar-Kyoto Rats (WKY). They hypothesized that SHR would exhibit autonomic and endothelial dysfunctions, including increased inflammatory responses. Differences in femoral sympathetic nerve activity (fSNA) (innervation of bone marrow [BM]), alpha2a/beta2-adrenergic receptor expression, BM norepinephrine, BM imflammatory cells (ICs), edothelial progenitor cells (EPCs), and in vivo activity of the hypothalamic paraventricular nucleus (PVN)using MeMRI and GFP-pseudorabies virus (PRV)retrograde tracing. It is known that sympathetic drive in rats peaks at approximately 8pm and drops to its lowest levels around 11am, so most factors were measured both during the day and at night to review any possible changes in circadian-related sympathetic drive. Following the studies it was found that fSNA was increased 80% at night in the SHR compared to the WKY. There was also increased BM Nor and BM ICs during both the day and night in SHRs compared to WKY. Contrarily, BM EPCs were seen to decrease in SHR compared to WKY both during the day and night. However, blood ICs and blood EPCs were not seen to change from day to night time levels in the SHRs. Based upon the fact that IC's are known to compromise vascular integrity and EPCs are known to repair vascular damage, these results are conclusive with the hypothesis made. In order to compare sympathetic to parasympathetic drive in these animals levels of acetylcholine transferase and acetylcholine esterase were also measured showing decreases in both enzymes in the SHR population compared to the WKYs, insinuating a disregulation of sympathetic to parasympathetic drive. To support this, levels of fSNA were found to be significantly higher (25%)in SHR compared to normotensive control rats. Finally, both MeMRI and PRV retrograde tracing both revealed increased levels of in vivo neuronal activity of the PVN in SHRs compared to WKYs. Conclusively, this study showed an improper circadian-related balance between sympathetic and parasympathetic drive to immune organs (BM) that may be playing a role in perpetuating neurogenic hypertension. ~JI

Mapping of the habenulo-interpeduncular pathway in living mice using manganese-enhanced 3D MRI.

Magn Reson Imaging. 2006 Apr;24(3):209-15. Epub 2006 Jan 6. Watanabe T, Radulovic J, Boretius S, Frahm J, Michaelis T. I chose this paper because I've been wondering about intercerebroventricular (ICV) injections for MEMRI studies. In this paper, the authors wanted to use memri to map the habenula (Hb) , so they injected MnCl2 in to left ventricle. They were able to trace fibers from Hb (near ventricle) to the interpeduncular nucleus (IP), however the reproducability was variable. They proposed that contact with the choroid plexus may have removed much of the Mn and introduced the variability in CSF manganese concentration. They then went on to scan the Hb and the IP at 2, 6, and 24 hours after a subcutaneous injection and found that 6hr gave the best signal to noise ratio. They note that the Hb showed the increase before its projections and say that this is evidence of anterograde Mn transport, but I don't entirely agree with making that jump in reasoning since I'm pretty sure a few groups mention that areas closer to CSF/blood tend to light up earlier, regardless of projections. Anyway, this paper introduces the issue of the choroid plexus interfering with ICV injections, something I hadn't accounted for and, apparently, neither did the authors. Things are always more complicated than we want them to be. -DH

Abstract: Manganese Enhanced MRI Assay of Spinal Cord Functional Connectivity

By: Xiaowei Zhang, Naomi Santa Maria, Samuel Barnes, and Russell E. Jacobs These studies looked to develop manganese-enhanced MRI for the examination of longitudinal spinal cord injury therapies. Previous to MeMRI extensive histology was needed on spinal tissue in order to characterize different therapies, these techniques however prevented longitudinal follow-up. Utilizing manganese as a retrograde tracer, 2,000 nanoliters of 200 mM MnCl2 was injected through a burr hole in the right lamina of adult female mice. The entire spinal cord and caudal portion of the brain were then imaged for four 400 micron sagittal T1 weighted slices 30 min, 8, 24, 48 and 72 hours after the injections. Interestingly, they were able watch manganese travel up the spinal cord into the brain stem, which pertains to what I am looking to do in the future. They saw that manganese intensity increased in the caudal part of the brain at 72 hours which is 24 hours post the time we are currently imaging the RVLM after spinal cord injections. We will be looking to examine a more acute time course of manganese uptake following spinal injections over the last month, this includes imaging the RVLM every 8 hours after injections. At some point it would be ideal to mimic these studies and observe manganese transport up the cord. However, more preliminary studies must first be done to facilitate this. ~JI

New method of manganese-enhanced Magnetic Resonance Imaging (MEMRI) for rat brain research.

Exp Anim. 2012;61(2):157-64. Jeong KY, Lee C, Cho JH, Kang JH, Na HS. In this paper, they wanted to figure out what they believed to be the best way to do MeMRI - using intracerebroventricular administration (ICV) of Mn, similar to what we have recently discussed. They conducted their by using T1-Weighted scans following 50uL injections of 20, 30, 40, 60, and 80mM MnCl2 in to the cisterna magna, tracing signal enhancement over the next 4 days. They found that 20mM injections produced the fewest toxic side effects and that larger concentrations were sometimes lethal. Signal enhancement was seen as early as 1hr after Mn administration, but only in circumventricular areas. After 7hr there was a general, but heterogenous, signal enhancement. The signal continued to spread out, but was too intense to analyze at 14 and 19hrs. Their best enhancement was at 24hr after injection, and the signal began to decrease until they stopped imaging at 96hr post-administration. So this paper was cool because they answered a couple of questions I've been having. However, it did not address activity-dependent uptake like I would want to do. It seems like their entire goal was to look at brain structure, regardless of the effect on the animal. For the functional studies I would like to do, it might be better to use a lower dose of Mn and measure at 12-14hours. -DH

Reflex effects of stimulation of carotid sinus and aortic baroreceptors on hindlimb vascular resistance in dogs

Dampney, Roger AL, Michael G. Taylor, and Elspeth M. McLachian. "Reflex effects of stimulation of carotid sinus and aortic baroreceptors on hindlimb vascular resistance in dogs." Circulation research 29.2 (1971): 119-127. Before this study, published in 1971, the baroreflex had been established as a regulator of cardiovascular circulation via sensory receptors known as the carotid sinus and aortic baroreceptors. As their names describe, these two sets of sensory receptors are located on blood vessels in the carotid bodies on either side of the neck and at the level of the aortic arch. Each set of receptors are sensitive to the stretching of the vascular wall, and we now know that when stimulated they will relay information to the NTS which plays a role in modulating sympathetic outflow from the RVLM via GABAergic inhibition from the CVLM. At the time the baroreceptors located in the carotid bodies had been characterize much more extensively than the receptors located at the aortic arch. The goal then of this study was to define reflex changes following variations of aortic stimulation as well as compare the sensitivity of the aortic receptors to the already defined carotid receptors. To do this, two experimental setups were used. In both set ups canine hindlimbs were perfused at the level of the abdominal aorta directly below the bifurcation of the renal arteries. Blood was perfused into the hindlimbs at a constant rate using a pulsitile pump to mimic a heartbeat, and arterial pressure in the hindlimbs was measured from a branch of one of the femoral arteries. In the first set of experiments the carotid receptors were isolated and the vessels were perfused at a constant pressure to ensure no sensory information was being relayed to the brain. In this way, they were able to ensure that the reflex changes being observed were strictly from the aortic receptors. In the second experiment the opposite was done and the vagi were cut diminishing sensory information from the aortic receptors. After stimulation of the aortic receptors at different frequencies, what was found is that at a specific frequency of stimulation, compared to the carotid receptors, the aortic receptors did not produce as large of a reflex change seen at the level of the hindlimb vasculature. For example the maximal gain observed from stimulation of the aortic receptors was 1.1, where as the maximal gain observed from stimulation of the carotid receptors was 2.2. These observations allowed for the conclusion that aortic baroreceptor have lower sensitivity to changes in blood pressure than the carotid baroreceptors, in a way that greater changes in pressure must occur for the aortic receptors to induces changes in vascular resistance at the level of the hindlegs. ~JI

Differential modulation of sympathetic and respiratory activities by cholinergic mechanisms in the nucleus of the solitary tract in rats.

Exp Physiol. 2014 Apr 11. [Epub ahead of print] Furuya WI, Bassi M, Menani JV, Colombari E, Zoccal DB, Colombari DS. I chose this paper because it was another relevant and recent one from my EB mentor, Debora Colombari. In it, they looked at the contributions of ACh signaling in the intermediate NTS (iNTS) and the caudal NTS (cNTS) to the phrenic nerve activity (PNA) and sympathetic nerve activity (SNA; thoracic sympathetic chain), with an emphasis on the NTS's roles in the baroreflex and peripheral chemoreflex. They found that injecting ACh into the iNTS inhibited SNA and PNA, but injections into the cNTS increased PNA without changing mean SNA (though it did change the pattern). Non-selective blockade of ACh receptors with mecamylamie (but not muscarinic blockade with atropine) in the iNTS blocked the ACh-induced effects on SNA and PNA. These blockades in the iNTS could also not alter baro- and chemoreflexes - so these must have been nicotinic-mediated effects. The cNTS was a little more complicated in that non-selective ACh blockade aboloshed the effect of ACh, but muscarinic blockade only reduced it - suggesting both receptor types are involved. However, PNA chemoreflex responses were reduced by mecamylamine but not atropine. The take-home message here is that different subnuclei of the NTS contribute differently to chemo- and baroreflexes, and that the NTS contributes to chemoreflex mainly through nicotinic activation. -DH

Lesion of the commissural nucleus of the solitary tract/A2 noradrenergic neurons facilitates the activation of angiotensinergic mechanisms in response to hemorrhage.

Neuroscience. 2013 Dec 19;254:196-204. doi: 10.1016/j.neuroscience.2013.09.017. Epub 2013 Sep 20. Freiria-Oliveira AH1, Blanch GT, De Paula PM, Menani JV, Colombari DS. I'll be honest, I chose this week's papers based on the fact that they came from the lab of my EB2014 meeting mentor, Débora Colombari. I was not very familiar with the work from this lab before EB, but it turns out they work on the NTS and AT1, which is something our lab has talked about on a number of occasions. In this paper, they used anti-dbh-sapporin to lesion the noradrenergic cells in the NTS, a.k.a the A2 group. They then induced a pretty heavy 4-step hemorrhage in rats and looked at the how a lack of the A2 group affects blood pressure. If you're curious about the proximity of the RVLM to the NTS and if their lesions might have affected the C1 neurons (which was my first thought), their first figure in the paper shows that while the NTS had a huge reduction in TH-positive cells, the RVLM appeared to be in perfect shape. Anyway, what they found was that lesioned rats actually recovered their blood pressure FASTER than control rats after hemmorhage, and that application of losartan (iv or intracerebroventricular) could block this change. Their argument is that A2 neurons probably work to inhibit angiotensinergic pathways. I don't claim to know all the neural microcircuitry, but since we're an RVLM lab... maybe we can claim that it's all because of NTS-CVLM-RVLM-RSNA? -DH