scholarly journals Developmental regulation of inhibitory synaptic currents in the dorsal motor nucleus of the vagus in the rat

2016 ◽  
Vol 116 (4) ◽  
pp. 1705-1714 ◽  
Author(s):  
Caitlin A. McMenamin ◽  
Laura Anselmi ◽  
R. Alberto Travagli ◽  
Kirsteen N. Browning
Keyword(s):  
Receptor Antagonist ◽  
Postnatal Development ◽  
Glycine Receptor ◽  
Inhibitory Synapses ◽  
Motor Nucleus ◽  
Early Postnatal Development ◽  
Postnatal Maturation ◽  
Synaptic Inputs ◽  
Time Points ◽  
Dorsal Motor Nucleus

Prior immunohistochemical studies have demonstrated that at early postnatal time points, central vagal neurons receive both glycinergic and GABAergic inhibitory inputs. Functional studies have demonstrated, however, that adult vagal efferent motoneurons receive only inhibitory GABAergic synaptic inputs, suggesting loss of glycinergic inhibitory neurotransmission during postnatal development. The purpose of the present study was to test the hypothesis that the loss of glycinergic inhibitory synapses occurs in the immediate postnatal period. Whole cell patch-clamp recordings were made from dorsal motor nucleus of the vagus (DMV) neurons from postnatal days 1–30, and the effects of the GABAA receptor antagonist bicuculline (1–10 μM) and the glycine receptor antagonist strychnine (1 μM) on miniature inhibitory postsynaptic current (mIPSC) properties were examined. While the baseline frequency of mIPSCs was not altered by maturation, perfusion with bicuculline either abolished mIPSCs altogether or decreased mIPSC frequency and decay constant in the majority of neurons at all time points. In contrast, while strychnine had no effect on mIPSC frequency, its actions to increase current decay time declined during postnatal maturation. These data suggest that in early postnatal development, DMV neurons receive both GABAergic and glycinergic synaptic inputs. Glycinergic neurotransmission appears to decline by the second postnatal week, and adult neurons receive principally GABAergic inhibitory inputs. Disruption of this developmental switch from GABA-glycine to purely GABAergic transmission in response to early life events may, therefore, lead to adverse consequences in vagal efferent control of visceral functions.

Role of Synaptic Inputs in Determining Input Resistance of Developing Brain Stem Motoneurons

2000 ◽  
Vol 84 (5) ◽  
pp. 2317-2329 ◽  
Author(s):  
Pedro A. Núñez-Abades ◽  
John M. Pattillo ◽  
Tracy M. Hodgson ◽  
William E. Cameron
Keyword(s):  
Receptor Antagonist ◽  
Brain Stem ◽  
Glycine Receptor ◽  
Age Groups ◽  
Input Resistance ◽  
Developing Brain ◽  
Inhibitory Synapses ◽  
Combined Application ◽  
Electrode Recording ◽  
Gaba Transmission

The contribution of synaptic input to input resistance was examined in 208 developing genioglossal motoneurons in 3 postnatal age groups (5–7 day, 13–16 day, and 18–24 day) using sharp electrode recording in a slice preparation of the rat brain stem. High magnesium (Mg2+; 6 mM) media generated significant increases (21–38%) in both the input resistance ( R n) and the first time constant (τ0) that were reversible. A large percent of the conductance blocked by high Mg2+ was also sensitive to tetrodotoxin (TTX). Little increase in resistance was attained by adding blockers of specific amino acid (glutamate, glycine, and GABA) transmission over that obtained with the high Mg2+. Comparing across age groups, there was a significantly larger percent change in R n with the addition of high Mg2+ at postnatal days 13 to 15 ( P13–15; 36%) than that found at P5–6 (21%). Spontaneous postsynaptic potentials were sensitive to the combined application of glycine receptor antagonist, strychnine, and the GABAA receptor antagonist, bicuculline. Application of either 10 μM strychnine or bicuculline separately produced a reversible increase in both R n and τ0. Addition of 10 μM bicuculline to a strychnine perfusate failed to further increase either R n or τ0. The strychnine/bicuculline-sensitive component of the total synaptic conductance increased with age so that this form of neurotransmission constituted the majority (>60%) of the observed percent decrease in R n and τ0 in the oldest age group. The proportion of change in τ0 relative to R n following strychnine or high magnesium perfusate varied widely from cell to cell and from age to age without pattern. Based on a model from the literature, this pattern indicates a nonselective distribution of the blocked synaptic conductances over the cell body and dendrites. Taken together, the fast inhibitory synapses (glycine, GABAA) play a greater role in determining cell excitability in developing brain stem motoneurons as postnatal development progresses. These findings suggest that synaptically mediated conductances effect the membrane behavior of developing motoneurons.

Glutamate Mediates an Excitatory Influence of the Paraventricular Hypothalamic Nucleus on the Dorsal Motor Nucleus of the Vagus

2002 ◽  
Vol 88 (1) ◽  
pp. 49-63 ◽  
Author(s):  
Xueguo Zhang ◽  
Ronald Fogel
Keyword(s):  
Nmda Receptor ◽  
Firing Rate ◽  
Receptor Antagonist ◽  
Ampa Receptor ◽  
Kynurenic Acid ◽  
Electrical Current ◽  
The Other ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Stimulation Of

Data have shown that the paraventricular nucleus of the hypothalamus (PVN) and the dorsal motor nucleus of the vagus (DMNV) play important roles in the regulation of gastrointestinal function and eating behavior. Anatomical studies have demonstrated direct projections from the PVN to the DMNV and physiological studies showed that the DMNV mediates many of the effects of PVN stimulation and electrical current stimulation of the PVN excites a subset of DMNV neurons. The aim of this study was to characterize the role of glutamate receptors in the excitatory influence of the PVN on gut-related DMNV neurons. Using single-cell recording techniques, we determined the effects of kynurenic acid, 6-cyano-7-nitroquinoxalene-2,3-dione (CNQX), anddl-2-amino-5-phosphonopentanoic acid (dl-AP5) on the increase in firing rate due to electrical current stimulation of the PVN. In initial experiments, we studied 24 DMNV neurons excited by electrical current stimulation of the PVN. Kynurenic acid, a broad-spectrum glutamate receptor antagonist, prevented the PVN effect in 22 neurons and significantly attenuated the effect in the other cells. Nine of these neurons demonstrated an inhibition in firing rate with PVN stimulation after pretreatment with kynurenic acid. In a separate group of 12 neurons, we determined the effects of CNQX (1.2 nmol) injected into the DMNV. This AMPA receptor antagonist completely blocked the excitatory response to PVN stimulation of six DMNV neurons and significantly attenuated the response of the other six DMNV neurons. The addition of 1.2 nmol dl-AP5, a N-methyl-d-aspartate (NMDA) receptor antagonist, further attenuated the response to PVN stimulation in four of the five DMNV neurons that were still excited after CNQX treatment. The fifth neuron demonstrated PVN- induced inhibition of firing rate after treatment with CNQX and dl-AP5. In a separate group of 11 DMNV neurons excited by electrical stimulation of the PVN,dl-AP5 partially attenuated the excitatory responses of only four DMNV neurons and did not block the excitation of any cells. The mean latency (14 neurons tested) from the PVN to the DMNV was 37.71 ± 2.40 (SE) ms. Monosynaptic action potentials and excitatory postsynaptic potentials were demonstrated in three DMNV neurons by intracellular recording. Our results indicate that glutamate released from PVN neurons projecting to the DMNV excite the gut-related vagal motor neurons by acting predominantly on the AMPA receptor. The NMDA receptor plays only a minor role in the excitatory effect.

scholarly journals Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat

2017 ◽  
Vol 313 (5) ◽  
pp. G434-G441 ◽  
Author(s):  
L. Anselmi ◽  
L. Toti ◽  
C. Bove ◽  
R. A. Travagli
Keyword(s):  
Receptor Antagonist ◽  
Brain Stem ◽  
Sch 23390 ◽  
Systemic Administration ◽  
Membrane Properties ◽  
Receptor Subtype ◽  
Motor Nucleus ◽  
Gastric Tone ◽  
Dorsal Motor Nucleus ◽  
The Brain

Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1) assess the gastric effects of brain stem DA application, 2) identify the DA receptor subtype, and, 3) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway.

Δ9-Tetrahydrocannabinol selectively acts on CB1 receptors in specific regions of dorsal vagal complex to inhibit emesis in ferrets

2003 ◽  
Vol 285 (3) ◽  
pp. G566-G576 ◽  
Author(s):  
Marja D. Van Sickle ◽  
Lorraine D. Oland ◽  
Ken Mackie ◽  
Joseph S. Davison ◽  
Keith A. Sharkey
Keyword(s):  
Receptor Antagonist ◽  
Brain Stem ◽  
Area Postrema ◽  
Motor Nucleus ◽  
Cb1 Receptors ◽  
Dorsal Vagal Complex ◽  
Dorsal Motor Nucleus ◽  
Site Of Action ◽  
Fos Expression ◽  
The Brain

The aim of this study was to investigate the efficacy, receptor specificity, and site of action of Δ9-tetrahydrocannabinol (THC) as an antiemetic in the ferret. THC (0.05-1 mg/kg ip) dose-dependently inhibited the emetic actions of cisplatin. The ED50 for retching was ∼0.1 mg/kg and for vomiting was 0.05 mg/kg. A specific cannabinoid (CB)1 receptor antagonist SR-141716A (5 mg/kg ip) reversed the effect of THC, whereas the CB2 receptor antagonist SR-144528 (5 mg/kg ip) was ineffective. THC applied to the surface of the brain stem was sufficient to inhibit emesis induced by intragastric hypertonic saline. The site of action of THC in the brain stem was further assessed using Fos immunohistochemistry. Fos expression induced by cisplatin in the dorsal motor nucleus of the vagus (DMNX) and the medial subnucleus of the nucleus of the solitary tract (NTS), but not other subnuclei of the NTS, was significantly reduced by THC rostral to obex. At the level of the obex, THC reduced Fos expression in the area postrema and the dorsal subnucleus of the NTS. The highest density of CB1 receptor immunoreactivity was found in the DMNX and the medial subnucleus of the NTS. Lower densities were observed in the area postrema and dorsal subnucleus of the NTS. Caudal to obex, there was moderate density of staining in the commissural subnucleus of the NTS. These results show that THC selectively acts at CB1 receptors to reduce neuronal activation in response to emetic stimuli in specific regions of the dorsal vagal complex.

scholarly journals Nitric oxide controls excitatory/inhibitory balance in the hypoglossal nucleus during early postnatal development

2020 ◽  
Vol 225 (9) ◽  
pp. 2871-2884
Author(s):  
Federico Portillo ◽  
Bernardo Moreno-López
Keyword(s):  
Nitric Oxide ◽  
Postnatal Development ◽  
Chronic Administration ◽  
Inhibitory Synapses ◽  
Hypoglossal Nucleus ◽  
Sudden Infant ◽  
Early Postnatal Development ◽  
Synaptic Remodeling ◽  
Obstructive Sleep ◽  
Actomyosin Contraction

AbstractSynaptic remodeling during early postnatal development lies behind neuronal networks refinement and nervous system maturation. In particular, the respiratory system is immature at birth and is subjected to significant postnatal development. In this context, the excitatory/inhibitory balance dramatically changes in the respiratory-related hypoglossal nucleus (HN) during the 3 perinatal weeks. Since, development abnormalities of hypoglossal motor neurons (HMNs) are associated with sudden infant death syndrome and obstructive sleep apnea, deciphering molecular partners behind synaptic remodeling in the HN is of basic and clinical relevance. Interestingly, a transient expression of the neuronal isoform of nitric oxide (NO) synthase (NOS) occurs in HMNs at neonatal stage that disappears before postnatal day 21 (P21). NO, in turn, is a determining factor for synaptic refinement in several physiopathological conditions. Here, intracerebroventricular chronic administration (P7–P21) of the broad spectrum NOS inhibitor l-NAME (N(ω)-nitro-l-arginine methyl ester) differentially affected excitatory and inhibitory rearrangement during this neonatal interval in the rat. Whilst l-NAME led to a reduction in the number of excitatory structures, inhibitory synaptic puncta were increased at P21 in comparison to administration of the inactive stereoisomer d-NAME. Finally, l-NAME decreased levels of the phosphorylated form of myosin light chain in the nucleus, which is known to regulate the actomyosin contraction apparatus. These outcomes indicate that physiologically synthesized NO modulates excitatory/inhibitory balance during early postnatal development by acting as an anti-synaptotrophic and/or synaptotoxic factor for inhibitory synapses, and as a synaptotrophin for excitatory ones. The mechanism of action could rely on the modulation of the actomyosin contraction apparatus.

scholarly journals Depressed cardiac contractility and its postnatal development in rats after chemical sympathectomy

2008 ◽  
pp. 507-515
Author(s):  
J Švíglerová ◽  
J Kuncová ◽  
L Nalos ◽  
J Slavíková ◽  
M Štengl
Keyword(s):  
Left Ventricle ◽  
Right Ventricle ◽  
Neuropeptide Y ◽  
Postnatal Development ◽  
Cardiac Contractility ◽  
Papillary Muscles ◽  
Chemical Sympathectomy ◽  
Postnatal Maturation ◽  
Time Points ◽  
The Right

The contribution of the sympathetic innervation to the postnatal development of cardiac contractility remains unclear. In this study, the postnatal maturation of cardiac contractility was compared in control rats and rats after chemical sympathectomy. The chemical sympathectomy was induced by administration of 6-hydroxydopamine to newborn rats. At days 20, 40 and 60 of postnatal life, the contractile parameters and concentrations of sympathetic neurotransmitters were measured in both right and left ventricles. In rats with chemical sympathectomy, concentrations of norepinephrine were reduced almost completely in both ventricles at all time points. The contractility of the left ventricle papillary muscles was substantially decreased at all time points. In contrast, the contractility of the right ventricle papillary muscles was decreased only transiently, showing a recovery at day 60 regardless of the permanently decreased concentration of norepinephrine. The concentration of neuropeptide Y, another neurotransmitter present in sympathetic nerves, showed the same developmental trend as contractility: permanent reduction in the left ventricle, transient reduction with a recovery at day 60 in the right ventricle. The data indicate that the sympathetic nervous system plays an important role in the postnatal development of cardiac contractility and neuropeptide Y may contribute to this effect.

scholarly journals Development and long-term integration of MGE-lineage cortical interneurons in the heterochronic environment

2017 ◽  
Vol 118 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Phillip Larimer ◽  
Julien Spatazza ◽  
Michael P. Stryker ◽  
Arturo Alvarez-Buylla ◽  
Andrea R. Hasenstaub
Keyword(s):  
Pyramidal Cells ◽  
Developmental Time ◽  
Host Cells ◽  
Inhibitory Synapses ◽  
Input Output ◽  
Early Postnatal Development ◽  
Time Points ◽  
Fast Spiking ◽  
Output Characteristics

Interneuron precursors transplanted into visual cortex induce network plasticity during their heterochronic maturation. Such plasticity can have a significant impact on the function of the animal and is normally present only during a brief critical period in early postnatal development. Elucidating the synaptic and physiological properties of interneuron precursors as they mature is key to understanding how long-term circuit changes are induced by transplants. We studied the development of transplant-derived interneurons and compared it to endogenously developing interneurons (those that are born and develop in the same animal) at parallel developmental time points, using patch-clamp recordings in acute cortical slices. We found that transplant-derived interneurons develop into fast-spiking and non-fast-spiking neurons characteristic of the medial ganglionic eminence (MGE) lineage. Transplant-derived interneurons matured more rapidly than endogenously developing interneurons, as shown by more hyperpolarized membrane potentials, smaller input resistances, and narrower action potentials at a juvenile age. In addition, transplant-derived fast-spiking interneurons have more quickly saturating input-output relationships and lower maximal firing rates in adulthood, indicating a possible divergence in function. Transplant-derived interneurons both form inhibitory synapses onto host excitatory neurons and receive excitatory synapses from host pyramidal cells. Unitary connection properties are similar to those of host interneurons. These transplant-derived interneurons, however, were less densely functionally connected onto host pyramidal cells than were host interneurons and received fewer spontaneous excitatory inputs from host cells. These findings suggest that many physiological characteristics of interneurons are autonomously determined, while some factors impacting their circuit function may be influenced by the environment in which they develop. NEW & NOTEWORTHY Transplanting embryonic interneurons into older brains induces a period of plasticity in the recipient animal. We find that these interneurons develop typical fast-spiking and non-fast-spiking phenotypes by the end of adolescence. However, the input-output characteristics of transplant-derived neurons diverged from endogenously developing interneurons during adulthood, and they showed lower connection rates to local pyramidal cells at all time points. This suggests a unique and ongoing role of transplant-derived interneurons in host circuits, enabling interneuron transplant therapies.

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