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.

Role of Potassium Conductances in Determining Input Resistance of Developing Brain Stem Motoneurons

2000 ◽  
Vol 84 (5) ◽  
pp. 2330-2339 ◽  
Author(s):  
William E. Cameron ◽  
Pedro A. Núñez-Abades ◽  
Ilan A. Kerman ◽  
Tracy M. Hodgson
Keyword(s):  
Membrane Potential ◽  
Brain Stem ◽  
Barium Chloride ◽  
Input Resistance ◽  
Membrane Resistance ◽  
Electrode Recording ◽  
Percent Increase ◽  
Potassium Conductances ◽  
Brain Stem Slices

The role of potassium conductances in determining input resistance was studied in 166 genioglossal (GG) motoneurons using sharp electrode recording in brain stem slices of the rats aged 5–7 days, 13–15 days, and 19–24 days postnatal ( P). A high magnesium (Mg2+; 6 mM) perfusate was used to block calcium-mediated synaptic release while intracellular or extracellular cesium (Cs+) and/or extracellular tetraethylammonium (TEA) or barium (Ba2+) were used to block potassium conductances. In all cases, the addition of TEA to the high Mg2+ perfusate generated a larger increase in both input resistance ( R n) and the first membrane time constant (τ0) than did high Mg2+ alone indicating a substantial nonsynaptic contribution to input resistance. With intracellular injection of Cs+, GG motoneurons with lower resistance (<40 MΩ), on the average, showed a larger percent increase in R n than cells with higher resistance (>40 MΩ). There was also a significant increase in the effect of internal Cs+ on R n and τ0 with age. The largest percent increase (67%) in the τ0 due to intracellular Cs+ occurred at P13–15, a developmental stage characterized by a large reduction in specific membrane resistance. Addition of external Cs+blocked conductances (further increasing R n and τ0) beyond those blocked by the TEA perfusate. Substitution of external calcium with 2 mM barium chloride produced a significant increase in both R n and τ0at all ages studied. The addition of either intracellular Cs+ or extracellular Ba2+created a depolarization shift of the membrane potential. The amount of injected current required to maintain the membrane potential was negatively correlated with the control R n of the cell at most ages. Thus low resistance cells had, on the average, more Cs+- and Ba2+-sensitive channels than their high resistance counterparts. There was also a disproportionately larger percent increase in τ0 as compared with R n for both internal Cs+ and external Ba2+. Based on a model by Redman and colleagues, it might be suggested that the majority of these potassium conductances underlying membrane resistance are initially located in the distal dendrites but become more uniformly distributed over the motoneuron surface in the oldest animals.

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.

Dorsal and Ventral Distribution of Excitable and Synaptic Properties of Neurons of the Bed Nucleus of the Stria Terminalis

2003 ◽  
Vol 90 (1) ◽  
pp. 405-414 ◽  
Author(s):  
Regula E. Egli ◽  
Danny G. Winder
Keyword(s):  
Receptor Antagonist ◽  
Drugs Of Abuse ◽  
Input Resistance ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Adult Mice ◽  
Dependent Potential

The bed nucleus of the stria terminalis (BNST) is a structure uniquely positioned to integrate stress information and regulate both stress and reward systems. Consistent with this arrangement, evidence suggests that the BNST, and in particular the noradrenergic input to this structure, is a key component of affective responses to drugs of abuse. We have utilized an in vitro slice preparation from adult mice to determine synaptic and membrane properties of these cells, focusing on the dorsal and ventral subdivisions of the anterolateral BNST (dBNST and vBNST) because of the differential noradrenergic input to these two regions. We find that while resting membrane potential and input resistance are comparable between these subdivisions, excitable properties, including a low-threshold spike (LTS) likely mediated by T-type calcium channels and an Ih-dependent potential, are differentially distributed. Inhibitory and excitatory postsynaptic potentials (IPSPs and EPSPs, respectively) are readily evoked in both dBNST and vBNST. The fast IPSP is predominantly GABAA-receptor mediated and is partially blocked by the AMPA/kainate-receptor antagonist CNQX. In the presence of the GABAA-receptor antagonist picrotoxin, cells in dBNST but not vBNST are more depolarized and have a higher input resistance, suggesting tonic GABAergic inhibition of these cells. The EPSPs elicited in BNST are monosynaptic, exhibit paired pulse facilitation, and contain both an AMPA- and an N-methyl-d-aspartate (NMDA) receptor-mediated component. These data support the hypothesis that neurons of the dorsal and ventral BNST differentially integrate synaptic input, which is likely of behavioral significance. The data also suggest mechanisms by which information may flow through stress and reward circuits.

scholarly journals Computational Studies on Acquisition and Adaptation of Ocular Following Responses Based on Cerebellar Synaptic Plasticity

2002 ◽  
Vol 87 (3) ◽  
pp. 1554-1571 ◽  
Author(s):  
Kenji Yamamoto ◽  
Yasushi Kobayashi ◽  
Aya Takemura ◽  
Kenji Kawano ◽  
Mitsuo Kawato
Keyword(s):  
Synaptic Plasticity ◽  
Brain Stem ◽  
Visual Motion ◽  
Climbing Fiber ◽  
Inhibitory Synapses ◽  
Ocular Following ◽  
Mst Neurons ◽  
P Cells ◽  
The Brain

To investigate how cerebellar synaptic plasticity guides the acquisition and adaptation of ocular following response (OFR), a large-scale network model was developed. The model includes the cerebral medial superior temporal area (MST), Purkinje cells (P cells) of the ventral paraflocculus, the accessory optic and climbing fiber systems, the brain stem oculomotor network, and the oculomotor plant. The model reconstructed temporal profiles of both firing patterns of MST neurons and P cells and eye movements. Model MST neurons ( n = 1,080) were set to be driven by retinal error and exhibited 12 preferred directions, 30 preferred velocities, and 3 firing waveforms. Correspondingly, each model P cell contained 1,080 excitatory synapses from granule cell axons (GCA) and 1,080 inhibitory synapses. P cells ( n = 40) were classified into four groups by their laterality (hemisphere) and by preferred directions of their climbing fiber inputs (CF) (contralateral or upward). The brain stem neural circuit and the oculomotor plant were modeled on the work of Yamamoto et al. The initial synaptic weights on the P cells were set randomly. At the beginning, P cell simple spikes were not well modulated by visual motion, and the eye was moved only slightly by the accessory optic system. The synaptic weights were updated according to integral-differential equation models of physiologically demonstrated synaptic plasticity: long-term depression and long-term potentiation for GCA synapses and rebound potentiation for inhibitory synapses. We assumed that maximum plasticity was induced when GCA inputs preceded CF inputs by 200 ms. After more than 10,000 presentations of ramp-step visual motion, the strengths of both the excitatory and inhibitory synapses were modified. Subsequently, the simple spike responses became well developed, and ordinary OFRs were acquired. The preferred directions of simple spikes became the opposite of those of CFs. Although the model MST neurons were set to possess a wide variety of firing characteristics, the model P cells acquired only downward or ipsilateral preferred directions, high preferred velocities and stereotypical firing waveforms. Therefore the drastic transition of the neural representation from the population codes in the MST to the firing-rate codes of simple spikes were learned at the GCA-P cell synapses and inhibitory cells-P cell synapses. Furthermore, the model successfully reproduced the gain- and directional-adaptation of OFR, which was demonstrated by manipulating the velocity and direction of visual motion, respectively. When we assumed that synaptic plasticity could only occur if CF inputs preceded GCA inputs, the ordinary OFR were acquired but neither the gain-adaptation nor the directional adaptation could be reproduced.

Cholecystokinin-8s excites identified rat pancreatic-projecting vagal motoneurons

2007 ◽  
Vol 293 (2) ◽  
pp. G484-G492 ◽  
Author(s):  
Shuxia Wan ◽  
F. Holly Coleman ◽  
R. Alberto Travagli
Keyword(s):  
Brain Stem ◽  
Pancreatic Polypeptide ◽  
Potassium Conductance ◽  
Input Resistance ◽  
Exocrine Secretion ◽  
Motor Nucleus ◽  
Pancreatic Exocrine Secretion ◽  
Calcium Dependent ◽  
Synaptic Circuits ◽  
Pancreatic Exocrine

It is known that cholecystokinin (CCK) acts in a paracrine fashion to increase pancreatic exocrine secretion via vagal circuits. Recent evidence, however, suggests that CCK-8s actions are not restricted to afferent vagal fibers, but also affect brain stem structures directly. Within the brain stem, preganglionic neurons of the dorsal motor nucleus of the vagus (DMV) send efferent fibers to subdiaphragmatic viscera, including the pancreas. Our aims were to investigate whether DMV neurons responded to exogenously applied CCK-8s and, if so, the mechanism of action. Using whole cell patch-clamp recordings we show that perfusion with CCK-8s induced a concentration-dependent excitation in ∼60% of identified pancreas-projecting DMV neurons. The depolarization was significantly reduced by tetrodotoxin, suggesting both direct (on the DMV membrane) and indirect (on local synaptic circuits) effects. Indeed, CCK-8s increased the frequency of miniature excitatory currents onto DMV neurons. The CCK-A antagonist, lorglumide, prevented the CCK-8s-mediated excitation whereas the CCK-B preferring agonist, CCK-nonsulfated, had no effect, suggesting the involvement of CCK-A receptors only. In voltage clamp, the CCK-8s-induced inward current reversed at −106 ± 3 mV and the input resistance increased by 150 ± 15%, suggesting an effect mediated by the closure of a potassium conductance. Indeed, CCK-8s reduced both the amplitude and the time constant of decay of a calcium-dependent potassium conductance. When tested with pancreatic polypeptide (which reduces pancreatic exocrine secretion), cells that responded to CCK-8s with an excitation were, instead, inhibited by pancreatic polypeptide. These data indicate that CCK-8s may control pancreas-exocrine secretion also via an effect on pancreas-projecting DMV neurons.

Antagonism of the Antinocifensive Action of Halothane by Intrathecal Administration of GABA-A Receptor Antagonists

1996 ◽  
Vol 84 (5) ◽  
pp. 1205-1214 ◽  
Author(s):  
Peggy Mason ◽  
Casey A. Owens ◽  
Donna L. Hammond
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Glycine Receptor ◽  
Intrathecal Administration ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Receptor Antagonists ◽  
Response Latencies ◽  
Halothane Concentration

Background The hind brain and the spinal cord, regions that contain high concentrations of gamma-aminobutyric acid (GABA) and GABA receptors, have been implicated as sites of action of inhalational anesthetics. Previous studies have established that general anesthetics potentiate the effects of gamma-aminobutyric acid at the GABAA receptor. It was therefore hypothesized that the suppression of nocifensive movements during anesthesia is due to an enhancement of GABAA receptor-mediated transmission within the spinal cord. Methods Rats in which an intrathecal catheter had been implanted 1 week earlier were anesthetized with halothane. Core temperature was maintained at a steady level. After MAC determination, the concentration of halothane was adjusted to that at which the rats last moved in response to tail clamping. Saline, a GABAA, a GABAB, or glycine receptor antagonist was then injected intrathecally. The latency to move in response to application of the tail clamp was redetermined 5 min later, after which the halothane concentration was increased by 0.2%. Response latencies to application of the noxious stimulus were measured at 7-min intervals during the subsequent 35 min. To determine whether these antagonists altered baseline response latencies by themselves, another experiment was conducted in which the concentration of halothane was not increased after intrathecal administration of GABAA receptor antagonists. Results Intrathecal administration of the GABAA receptor antagonists bicuculline (0.3 micrograms) or picrotoxin (0.3, 1.0 micrograms) antagonized the suppression of nocifensive movement produced by the small increase in halothane concentration. In contrast, the antinocifensive effect of the increase in halothane concentration was not attenuated by the GABAB receptor antagonist CGP 35348 or the glycine receptor antagonist strychnine. By themselves, the GABAA receptor antagonists did not alter response latency in rats anesthetized with sub-MAC concentrations of halothane. Conclusions Intrathecal administration of bicuculline or picrotoxin, at doses that do not change the latency to pinch-evoked movement when administered alone, antagonized the suppression of noxious-evoked movement produced by halothane concentrations equal to or greater than MAC. These results suggest that enhancement of GABAA receptor-mediated transmission within the spinal cord contributes to halothane's ability to suppress nocifensive movements.

5-Hydroxytryptamine Responses in Immature Rat Rostral Ventrolateral Medulla Neurons In Vitro

1998 ◽  
Vol 80 (3) ◽  
pp. 1033-1041 ◽  
Author(s):  
L. L. Hwang ◽  
N. J. Dun
Keyword(s):  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Reversal Potential ◽  
Input Resistance ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Immature Rat ◽  
Apparent Change ◽  
Biphasic Responses

Hwang, L. L. and N. J. Dun. 5-Hydroxytryptamine responses in immature rat rostral ventrolateral medulla neurons in vitro. J. Neurophysiol. 80: 1033–1041, 1998. Whole cell patch recordings were made from rostral ventrolateral medulla (RVLM) neurons of brainstem slices from 8- to 12-day-old rats. By superfusion or pressure ejection to RVLM neurons, 5-hydroxytryptamine (5-HT) elicited three types of membrane potential changes: a slow hyperpolarization (5-HTH), a slow depolarization (5-HTD) and a biphasic response, which persisted in a tetrodotoxin (TTX, 0.3 μM)-containing solution. 5-HTH were accompanied by a decrease of input resistance in the majority of responsive neurons. Hyperpolarization reduced and depolarization increased the 5-HTH; the mean reversal potential was −92.3 mV in 3.1 mM and shifted to −69.3 mV in 7 mM [K+]o. Barium (Ba2+, 0.1 mM) but not tetraethylammonium (TEA, 10 mM) suppressed 5-HTH. The 5-HT1A receptor agonist (±)-8-hydroxy-dipropylamino-tetralin (8-OH-DPAT; 5–50 μM) hyperpolarized RVLM neurons. The 5-HT1A antagonist pindobind-5-HT1A (PBD; 1–3 μM) and the 5-HT2/5-HT1 receptor antagonist spiperone (1–10 μM) suppressed 5-HTH and the hyperpolarizing phase of biphasic responses; the 5-HT2 receptor antagonist ketanserin (3 μM) was without significant effect. 5-HTD were associated with an increase or no apparent change of input resistance in RVLM neurons. Hyperpolarization of the membrane decreased or caused no apparent change in 5-HTD. 5-HTD were reduced in an elevated [K+]o (7.0 mM) solution and >60% in a low Na+ (26 mM) solution and were not significantly changed in a low Cl− (6.7 mM) or Ca2+-free/high Mg2+ (10.9 mM) solution. The 5-HT2 receptor agonist α-methyl-5-HT (50 μM) depolarized RVLM neurons, and the 5-HT2 antagonist ketanserin (1–10 μM) attenuated the 5-HTD and the depolarizing phase of biphasic responses, whereas the 5-HT1A receptor antagonist PBD (2 μM) was without effect. Inclusion of the hydrolysis resistant guanine nucleotide GDP-β-S in patch solution significantly reduced the 5-HTH as well as the 5-HTD. The present study shows that, in the immature rat RVLM neurons, 5-HT causes a slow hyperpolarization and depolarization probably by interacting with 5-HT1A and 5-HT2 receptors, which are G-proteins coupled. 5-HTH may involve an increase of an inwardly rectifying K+ conductance, and 5-HTD appear to be caused by a decrease of K+ conductance and/or increase of nonselective cation conductance.

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