Institute for Integrative Physiology

Chicago, IL, United States

Institute for Integrative Physiology

Chicago, IL, United States
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DePuy S.D.,University of Virginia | DePuy S.D.,Institute for Integrative Physiology | Stornetta R.L.,University of Virginia | Bochorishvili G.,University of Virginia | And 4 more authors.
Journal of Neuroscience | Year: 2013

The C1 neurons are a nodal point for blood pressure control and other autonomic responses. Here we test whether these rostral ventrolateral medullary catecholaminergic (RVLM-CA) neurons use glutamate as a transmitter in the dorsal motor nucleus of the vagus (DMV). After injecting Cre-dependent adeno-associated virus (AAV2) DIO-Ef1α-channelrhodopsin2(ChR2)-mCherry (AAV2) into the RVLM of dopamine-β-hydroxylase Cre transgenic mice (DβHCre/0), mCherry was detected exclusively in RVLM-CA neurons. Within the DMV >95% mCherry-immunoreactive(ir) axonal varicosities were tyrosine hydroxylase (TH)-ir and the same proportion were vesicular glutamate transporter 2 (VGLUT2)-ir. VGLUT2-mCherry colocalization was virtually absent when AAV2 was injected into the RVLM of DβHCre/0;VGLUT2flox/flox mice, into the caudal VLM (A1 noradrenergic neuron-rich region) of DβHCre/0 mice or into the raphe of ePetCre/0 mice. Following injection of AAV2 into RVLM of TH-Cre rats, phenylethanolamine N-methyl transferase and VGLUT2 immunoreactivities were highly colocalized in DMV within EYFP-positive or EYFP-negative axonal varicosities. Ultrastructurally, mCherry terminals from RVLM-CA neurons in DβHCre/0 mice made predominantly asymmetric synapses with choline acetyl-transferase-ir DMV neurons. Photostimulation of ChR2-positive axons in DβHCre/0 mouse brain slices produced EPSCs in 71% of tested DMV preganglionic neurons (PGNs) but no IPSCs. Photostimulation (20 Hz) activated PGNs up to 8 spikes/s (current-clamp). EPSCs were eliminated by tetrodotoxin, reinstated by 4-aminopyridine, and blocked by ionotropic glutamate receptor blockers. In conclusion, VGLUT2 is expressed by RVLM-CA (C1) neurons in rats and mice regardless of the presence of AAV2, the C1 neurons activate DMV parasympathetic PGNs monosynaptically and this connection uses glutamate as an ionotropic transmitter. © 2013 the authors.


Peng Y.-J.,Institute for Integrative Physiology | Nanduri J.,Institute for Integrative Physiology | Zhang X.,Institute for Integrative Physiology | Wang N.,Institute for Integrative Physiology | And 4 more authors.
Journal of Applied Physiology | Year: 2012

The objectives of the present study were to examine the effects of intermittent hypoxia (IH) on arterial baroreflex function and assess the underlying mechanism(s). Experiments were performed on adult male rats treated with 14 days of IH (15 s of hypoxia, 5 min of normoxia; 8 h/day) or normoxia (control). Arterial blood pressures were elevated in IH-treated rats, and this effect was associated with attenuated heart rate and splanchnic sympathetic nerve responses to arterial baroreflex activation. In IH-treated rats, carotid baroreceptor responses to elevated sinus pressures were attenuated. Endothelin-1 (ET-1) levels were elevated in the carotid sinus region of IH-treated rats, and this effect was associated with increased endothelin converting enzyme (ECE) activity, which generates biologically active ET-1. ETA receptor antagonist prevented the effects of IH on carotid baroreceptor activity. In IH-treated rats, reactive oxygen species (ROS) levels were elevated in the carotid sinus region, and antioxidant treatment prevented the effects of IH on ET-1 levels, ECE activity, carotid baroreceptor activity, and baroreflex function. These results demonstrate that 1) IH attenuates arterial baroreflex function, which is in part due to reduced carotid baroreceptor responses to elevated carotid sinus pressure, and 2) IH-induced carotid baroreceptor dysfunction involves reactive oxygen speciesdependent upregulation of ET-1 signaling in the carotid sinus region. Copyright © 2012 the American Physiological Society.

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