Immunoreactivity for the NMDA NR1 subunit in bulbospinal catecholamine and serotonin neurons of rat ventral medulla

Llewellyn‐Smith, Ida J.; Mueller, Patrick

doi:10.1016/j.autneu.2013.02.024

Cited by 12 publications

(42 citation statements)

References 46 publications

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“…The placement of CTB injections was confirmed in five of six active rats and five of five sedentary rats. In these animals, the locations of the injection sites and the spread of CTB rostrocaudally and dorsoventrally were similar to those in our previous report (Llewellyn‐Smith and Mueller, ). All injections were centered on the T10 IML, and tracer was present in the IML region for approximately one spinal segment rostrally and approximately one spinal segment caudally.…”

Section: Resultssupporting

confidence: 86%

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Physical (in)activity‐dependent structural plasticity in bulbospinal catecholaminergic neurons of rat rostral ventrolateral medulla

Mischel

Llewellyn‐Smith

Mueller

2013

J of Comparative Neurology

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Increased activity of the sympathetic nervous system is thought to play a role in the development and progression of cardiovascular disease. Recent work has shown that physical inactivity versus activity alters neuronal structure in brain regions associated with cardiovascular regulation. Our physiological studies suggest that neurons in the rostral ventrolateral medulla (RVLM) are more responsive to excitation in sedentary versus physically active animals. We hypothesized that enhanced functional responses in the RVLM may be due, in part, to changes in the structure of RVLM neurons that control sympathetic activity. We used retrograde tracing and immunohistochemistry for tyrosine hydroxylase (TH) to identify bulbospinal catecholaminergic (C1) neurons in sedentary and active rats after chronic voluntary wheel-running exercise. We then digitally reconstructed their cell bodies and dendrites at different rostrocaudal levels. The dendritic arbors of spinally-projecting TH neurons from sedentary rats were more branched than those of physically active rats (p<0.05). In sedentary rats, dendritic branching was greater in more rostral versus more caudal bulbospinal C1 neurons whereas, in physically active rats, dendritic branching was consistent throughout the RVLM. In contrast, cell body size and the number of primary dendrites did not differ between active and inactive animals. We suggest that these structural changes provide an anatomical underpinning for the functional differences observed in our in vivo studies. These inactivity-related structural and functional changes enhance the overall sensitivity of RVLM neurons to excitatory stimuli and may contribute to an increased risk of cardiovascular disease in sedentary individuals.

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Section: Resultssupporting

confidence: 86%

“…Injection placement was confirmed as previously described (Llewellyn‐Smith and Mueller, ), with slight modification. Lower thoracic segments were removed from the perfused spinal cords of all rats.…”

Section: Methodsmentioning

confidence: 99%

Physical (in)activity‐dependent structural plasticity in bulbospinal catecholaminergic neurons of rat rostral ventrolateral medulla

Mischel

Llewellyn‐Smith

Mueller

2013

J of Comparative Neurology

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“…Similarly, the average number of cells captured from the sedentary rats on the right and left side are 350 ± 29 and 359 ± 66 respectively. Fluorescently labeled cells were captured throughout the classically defined portion of the cardiovascular region of the RVLM (500 μm caudal and 150-μm rostral to the caudal pole of the facial nucleus) (Llewellyn-Smith and Mueller, 2013;Schreihofer and Sved, 2011). However, the majority of the cells collected were from the caudal 500 μm of the RVLM as shown by the rostro-caudal distribution of Fluorogold-positive neurons in sedentary and active (Figure 4B).…”

Section: Resultsmentioning

confidence: 99%

“…Using the caudal pole of the facial nucleus as a landmark, slides were selected for laser capture microdissection (Figure 1). Only slides containing sections which were 500 μm caudal or 150 μm rostral to the caudal pole of the facial nucleus were used based on previous reports suggesting this 650 μm region contains spinally-projecting RVLM neurons (Llewellyn-Smith and Mueller, 2013;Mischel, Llewellyn-Smith, and Mueller, 2014;Schreihofer and Sved, 2011). …”

Section: Methodsmentioning

confidence: 99%

Physical activity correlates with glutamate receptor gene expression in spinally-projecting RVLM neurons: A laser capture microdissection study

2014

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Physical inactivity is an important risk factor in the development of cardiovascular disease. The rostral ventrolateral portion of the medulla (RVLM) is composed of heterogeneous populations of neurons that are involved in the regulation of the cardiovascular system. Because of functional heterogeneity, studying the changes in the gene expression of this specific population of neurons within the RVLM is challenging. In the present study, a fluorescent retrograde tracer was injected into the spinal cord to specifically label bulbospinal RVLM neurons in sedentary and active rats. Laser capture microdissection (LCM) was then employed to collect the fluorescently labeled neurons from sections encompassing the rostrocaudal extent of the RVLM. RNA extracted from the neurons was used in qRT-PCR analysis. Changes in gene expression levels of glutamate and GABA receptor subunits were compared between sedentary and physically active rats. GLUR3 subunit showed a significant negative correlation between total running distance and its relative gene expression in active rats. There were no significant difference in the gene expression of NMDA (NR1, NR2A, NR2B, NR2C and NR2D), AMPA (GLUR1, GLUR2 and GLUR3) and GABAA (GABAA1 and GABAA2) receptor subunits. Overall, the present study demonstrates the feasibility of utilizing LCM to investigate the gene expression changes in a specific population of neurons in the RVLM. Correlation studies suggest that physical activity could contribute to neuroplasticity in the RVLM.

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“…The obligatory GluN1 subunit of the heteromeric, ionotropic NMDA receptor (Dingledine et al, 1999) is expressed in the RVLM (Llewellyn-Smith and Mueller, 2013). .…”

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Sex differences in NMDA GluN1 plasticity in rostral ventrolateral medulla neurons containing corticotropin-releasing factor type 1 receptor following slow-pressor angiotensin II hypertension

et al. 2015

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There are profound, yet incompletely understood, sex differences in the neurogenic regulation of blood pressure. Both corticotrophin signaling and glutamate receptor plasticity, which differ between males and females, are known to play important roles in the neural regulation of blood pressure. However, the relationship between hypertension and glutamate plasticity in corticotrophin-releasing hormone (CRF) receptive neurons in brain cardiovascular regulatory areas, including the rostral ventrolateral medulla (RVLM) and paraventricular nucleus of the hypothalamus (PVN), is not understood. In the present study, we used dual label immunoelectron microscopy to analyze sex differences in slow-pressor angiotensin II (AngII) hypertension with respect to the subcellular distribution of the obligatory GluN1 subunit of the N-methyl-D-aspartate receptor (NMDAR) in the RVLM and PVN. Studies were conducted in mice expressing the enhanced green fluorescence protein (EGFP) under the control of the CRF type 1 receptor (CRF1) promoter (i.e., CRF1-EGFP reporter mice). By light microscopy, GluN1-immunoreactivity was found in CRF1-EGFP neurons of the RVLM and PVN. Moreover, in both regions tyrosine hydroxylase was found in CRF1-EGFP neurons. In response to AngII, male mice showed an elevation in blood pressure that was associated with an increase in the proportion of GluN1 on presumably functional areas of the plasma membrane in CRF1-EGFP dendritic profiles in the RVLM. In female mice, AngII was neither associated with an increase in blood pressure nor an increase in plasma membrane GluN1 in the RVLM. Unlike the RVLM, AngII-mediated hypertension had no effect on GluN1 localization in CRF1-EGFP dendrites in the PVN of either male or female mice. These studies provide an anatomical mechanism for sex-differences in the convergent modulation of RVLM catecholaminergic neurons by CRF and glutamate. Moreover, these results suggest that sexual dimorphism in AngII-induced hypertension is reflected by NMDA receptor trafficking in presumptive sympathoexcitatory neurons in the RVLM.

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Immunoreactivity for the NMDA NR1 subunit in bulbospinal catecholamine and serotonin neurons of rat ventral medulla

Cited by 12 publications

References 46 publications

Physical (in)activity‐dependent structural plasticity in bulbospinal catecholaminergic neurons of rat rostral ventrolateral medulla

Physical (in)activity‐dependent structural plasticity in bulbospinal catecholaminergic neurons of rat rostral ventrolateral medulla

Physical activity correlates with glutamate receptor gene expression in spinally-projecting RVLM neurons: A laser capture microdissection study

Sex differences in NMDA GluN1 plasticity in rostral ventrolateral medulla neurons containing corticotropin-releasing factor type 1 receptor following slow-pressor angiotensin II hypertension

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