Article

C1 catecholamine neurons form local circuit synaptic connections within the rostroventrolateral medulla of rat.

Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, United States.
Neuroscience (Impact Factor: 3.33). 10/2012; 227. DOI: 10.1016/j.neuroscience.2012.09.049
Source: PubMed

ABSTRACT C1 catecholamine neurons reside within the rostroventrolateral medulla (RVLM), an area that plays an integral role in blood pressure regulation through reticulospinal projections to sympathetic preganglionic neurons in the thoracic spinal cord. In a previous investigation we mapped the efferent projections of C1 neurons, documenting supraspinal projections to cell groups in the preautonomic network that contribute to the control of cardiovascular function. Light microscopic study also revealed putative local circuit connections within RVLM. In this investigation we tested the hypothesis that RVLM C1 neurons elaborate a local circuit synaptic network that permits communication between C1 neurons giving rise to supraspinal and reticulospinal projections. A replication defective lentivirus vector that expresses enhanced green fluorescent protein (EGFP) under the control of a synthetic dopamine beta hydroxylase (DβH) promoter was used to label C1 neurons and their processes. Confocal fluorescence microscopy demonstrated thin varicose axons immunopositive for EGFP and tyrosine hydroxylase that formed close appositions to C1 somata and dendrites throughout the rostrocaudal extent of the C1 area. Dual-labeled electron microscopic analysis revealed axosomatic, axodendritic and axospinous synaptic contacts with C1 and non-C1 neurons with a distribution recapitulating that observed in the light microscopic analysis. Labeled boutons were large, contained light axoplasm, lucent spherical vesicles, and formed asymmetric synaptic contacts. Collectively these data demonstrate that C1 neurons form an asynaptic network within the C1 area that may function to coordinate activity among projection-specific subpopulations of neurons. The data also suggest that the boundaries of RVLM should be defined on the basis of function criteria rather than the C1 phenotype of neurons.

1 Follower
 · 
130 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypoglycemia elicits physiological and behavioral responses which are mediated in part by neurons within the ventrolateral medulla (VLM). The present study describes the neurochemistry of neurons activated by glucoprivation (2-deoxy-D-glucose, 2DG), specifically those within regions containing the A1, caudal C1 (cC1) and rostral C1 (rC1) cell groups. 2DG induced c-Fos immunoreactivity throughout the VLM. Activated neurons expressing prepro-cocaine and amphetamine-regulated transcript (PPCART), neuropeptide Y (NPY), glutamic acid decarboxylase (GAD67) or prepro-enkephalin (PPE) mRNA and/or immunoreactivity (-ir) for tyrosine hydroxylase (TH) were identified. TH(+) neurons were recruited in a dose-dependent manner. At high doses of 2DG [400 mg/kg, (n = 6)], 76 ± 1.2 % of activated neurons were TH(+) representing 52 ± 1.3 % of the total TH population. Virtually all activated neurons in the A1 and cC1 regions but only 60 % in the rC1 region were TH(+). Within the A1 region, TH(+), TH(+)NPY(+) and TH(+)NPY(+)PPE(+) subpopulations were activated and likely regulate vasopressin, oxytocin, and corticotrophin releasing hormone (CRH) from the hypothalamus. Within the cC1 region, non-TH neurons, TH(+)NPY(+), TH(+)NPY(+)PPCART(+), and TH(+)NPY(+)PPE(+) subpopulations were activated, likely regulating autonomic hypothalamic neurons or CRH and thyrotropin releasing hormone secretion. Within the rC1 region, non-TH neurons (40 % of those activated) were predominantly PPE(+) and were recruited by higher 2DG doses. Of the TH(+) activated neurons in the rC1 region, many expressed PPCART and half expressed NPY. The activated spinally projecting population was almost entirely TH(+)PPCART(+) and is likely to regulate adrenaline and glucagon release. These data indicate that glucoprivation activates at least nine phenotypically distinct populations of neurons in the VLM.
    Brain Structure and Function 10/2013; 220(1). DOI:10.1007/s00429-013-0642-3 · 4.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The C1 neurons reside in the rostral and intermediate portions of the ventrolateral medulla (RVLM, IVLM). They use glutamate as a fast transmitter and synthesize catecholamines plus various neuropeptides. These neurons regulate the hypothalamic pituitary axis via direct projections to the paraventricular nucleus and regulate the autonomic nervous system via projections to sympathetic and parasympathetic preganglionic neurons. The presympathetic C1 cells, located in the RVLM, are probably organized in a roughly viscerotopic manner and most of them regulate the circulation. C1 cells are variously activated by hypoglycemia, infection or inflammation, hypoxia, nociception and hypotension and contribute to most glucoprivic responses. C1 cells also stimulate breathing and activate brainstem noradrenergic neurons including the locus coeruleus. Based on the various effects attributed to the C1 cells, their axonal projections and what is currently known of their synaptic inputs, subsets of C1 cells appear to be differentially recruited by pain, hypoxia, infection/ inflammation, hemorrhage and hypoglycemia to produce a repertoire of stereotyped autonomic, metabolic and neuroendocrine responses that help the organism survive physical injury and its associated cohort of acute infection, hypoxia, hypotension and blood loss. C1 cells may also contribute to glucose and cardiovascular homeostasis in the absence of such physical stresses and C1 cell hyperactivity may contribute to the increase in sympathetic nerve activity (SNA) associated with diseases such as hypertension.
    AJP Regulatory Integrative and Comparative Physiology 05/2013; DOI:10.1152/ajpregu.00054.2013 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Catecholaminergic neurons of the rostral ventrolateral medulla (RVLM-CA neurons; C1 neurons) contribute to the sympathetic, parasympathetic and neuroendocrine responses elicited by physical stressors such as hypotension, hypoxia, hypoglycemia, and infection. Most RVLM-CA neurons express vesicular glutamate transporter (VGLUT)2, and may use glutamate as a ionotropic transmitter, but the importance of this mode of transmission in vivo is uncertain. To address this question, we genetically deleted VGLUT2 from dopamine-β-hydroxylase-expressing neurons in mice [DβH(Cre/0) ;VGLUT2(flox/flox) mice (cKO mice)]. We compared the in vivo effects of selectively stimulating RVLM-CA neurons in cKO vs. control mice (DβH(Cre/0) ), using channelrhodopsin-2 (ChR2-mCherry) optogenetics. ChR2-mCherry was expressed by similar numbers of rostral ventrolateral medulla (RVLM) neurons in each strain (~400 neurons), with identical selectivity for catecholaminergic neurons (90-99% colocalisation with tyrosine hydroxylase). RVLM-CA neurons had similar morphology and axonal projections in DβH(Cre/0) and cKO mice. Under urethane anesthesia, photostimulation produced a similar pattern of activation of presumptive ChR2-positive RVLM-CA neurons in DβH(Cre/0) and cKO mice. Photostimulation in conscious mice produced frequency-dependent respiratory activation in DβH(Cre/0) mice but no effect in cKO mice. Similarly, photostimulation under urethane anesthesia strongly activated efferent vagal nerve activity in DβH(Cre/0) mice only. Vagal responses were unaffected by α1 -adrenoreceptor blockade. In conclusion, two responses evoked by RVLM-CA neuron stimulation in vivo require the expression of VGLUT2 by these neurons, suggesting that the acute autonomic responses driven by RVLM-CA neurons are mediated by glutamate.
    European Journal of Neuroscience 11/2013; 39(1). DOI:10.1111/ejn.12421 · 3.67 Impact Factor

Full-text

Download
12 Downloads
Available from
Aug 10, 2014