scholarly journals 5-Hydroxytryptamine 2C receptors tonically augment synaptic currents in the nucleus tractus solitarii

2012 ◽  
Vol 108 (8) ◽  
pp. 2292-2305 ◽  
Author(s):  
James R. Austgen ◽  
Heather A. Dantzler ◽  
Brenna K. Barger ◽  
David D. Kline
Keyword(s):  
Membrane Potential ◽  
Brain Stem ◽  
Glutamate Release ◽  
Input Resistance ◽  
Receptor Activation ◽  
Nucleus Tractus Solitarii ◽  
Visceral Afferents ◽  
Receptor Blockade ◽  
Cardiorespiratory System ◽  
Epsc Amplitude

The nucleus tractus solitarii (nTS) is the primary termination and integration point for visceral afferents in the brain stem. Afferent glutamate release and its efficacy on postsynaptic activity within this nucleus are modulated by additional neuromodulators and transmitters, including serotonin (5-HT) acting through its receptors. The 5-HT2 receptors in the medulla modulate the cardiorespiratory system and autonomic reflexes, but the distribution of the 5-HT2C receptor and the role of these receptors during synaptic transmission in the nTS remain largely unknown. In the present study, we examined the distribution of 5-HT2C receptors in the nTS and their role in modulating excitatory postsynaptic currents (EPSCs) in monosynaptic nTS neurons in the horizontal brain stem slice. Real-time RT-PCR and immunohistochemistry identified 5-HT2C receptor message and protein in the nTS and suggested postsynaptic localization. In nTS neurons innervated by general visceral afferents, 5-HT2C receptor activation increased solitary tract (TS)-EPSC amplitude and input resistance and depolarized membrane potential. Conversely, 5-HT2C receptor blockade reduced TS-EPSC and miniature EPSC amplitude, as well as input resistance, and hyperpolarized membrane potential. Synaptic parameters in nTS neurons that receive sensory input from carotid body chemoafferents were also attenuated by 5-HT2C receptor blockade. Taken together, these data suggest that 5-HT2C receptors in the nTS are located postsynaptically and augment excitatory neurotransmission.

scholarly journals Presynaptic GABAB Receptors Regulate Retinohypothalamic Tract Synaptic Transmission by Inhibiting Voltage-Gated Ca2+ Channels

2006 ◽  
Vol 95 (6) ◽  
pp. 3727-3741 ◽  
Author(s):  
Mykhaylo G. Moldavan ◽  
Robert P. Irwin ◽  
Charles N. Allen
Keyword(s):  
Glutamate Release ◽  
Receptor Activation ◽  
Gabab Receptors ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Epsc Amplitude ◽  
Receptor Modulation ◽  
Joint Application ◽  
Retinohypothalamic Tract

Presynaptic GABAB receptor activation inhibits glutamate release from retinohypothalamic tract (RHT) terminals in the suprachiasmatic nucleus (SCN). Voltage-clamp whole cell recordings from rat SCN neurons and optical recordings of Ca2+-sensitive fluorescent probes within RHT terminals were used to examine GABAB-receptor modulation of RHT transmission. Baclofen inhibited evoked excitatory postsynaptic currents (EPSCs) in a concentration-dependent manner equally during the day and night. Blockers of N-, P/Q-, T-, and R-type voltage-dependent Ca2+ channels, but not L-type, reduced the EPSC amplitude by 66, 36, 32, and 18% of control, respectively. Joint application of multiple Ca2+ channel blockers inhibited the EPSCs less than that predicted, consistent with a model in which multiple Ca2+ channels overlap in the regulation of transmitter release. Presynaptic inhibition of EPSCs by baclofen was occluded by ω-conotoxin GVIA (≤72%), mibefradil (≤52%), and ω-agatoxin TK (≤15%), but not by SNX-482 or nimodipine. Baclofen reduced both evoked presynaptic Ca2+ influx and resting Ca2+ concentration in RHT terminals. Tertiapin did not alter the evoked EPSC and baclofen-induced inhibition, indicating that baclofen does not inhibit glutamate release by activation of Kir3 channels. Neither Ba2+ nor high extracellular K+ modified the baclofen-induced inhibition. 4-Aminopyridine (4-AP) significantly increased the EPSC amplitude and the charge transfer, and dramatically reduced the baclofen effect. These data indicate that baclofen inhibits glutamate release from RHT terminals by blocking N-, T-, and P/Q-type Ca2+ channels, and possibly by activation of 4-AP–sensitive K+ channels, but not by inhibition of R- and L-type Ca2+ channels or by Kir3 channel activation.

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.

Thyrotropin-releasing hormone (TRH) depolarizes a subset of inspiratory neurons in the newborn mouse brain stem in vitro

1996 ◽  
Vol 75 (2) ◽  
pp. 811-819 ◽  
Author(s):  
J. C. Rekling ◽  
J. Champagnat ◽  
M. Denavit-Saubie
Keyword(s):  
Membrane Potential ◽  
Brain Stem ◽  
Respiratory Rhythm ◽  
Input Resistance ◽  
Newborn Mouse ◽  
Hypoglossal Motoneurons ◽  
Inspiratory Neurons ◽  
Type 3

1. To extend the classification of respiratory neurons based on active membrane properties and discharge patterns to include responses to respiratory modulators, we have studied the effect of thyrotropin-releasing hormone (TRH, 1-5 microM) on the spontaneous respiratory-related neural activity in a thick brain stem slice preparation from the newborn mouse. The action of TRH on the respiratory output from the slice was investigated by recordings from the XII nerve. Cellular responses to TRH were investigated using whole cell recordings from hypoglossal motoneurons and three types of inspiratory neurons located in the rostral ventrolateral part of the slice. 2. Bath-applied TRH (1 microM) decreased the time between inspiratory discharges recorded on the XII nerve from 12.3 +/- 3.3 s to 4.9 +/- 1.1 s (n = 28; means +/- SD), i.e., caused an approximate threefold increase in the respiratory frequency. The coefficient of variation of the time between the inspiratory discharges decreased by one-half. Thus the respiratory output became more stable in response to TRH. The duration of the inspiratory discharges increased from 474 +/- 108 ms to 679 +/- 114 ms, and the amplitude decreased by 24%. An increase in the interdischarge noise on the XII nerve was recorded in the early phase of the TRH application. 3. Anatomically identified hypoglossal motoneurons (7 cells) responded to bath applied TRH with a depolarization eliciting spikes between the inspiratory potentials. The depolarization was accompanied by an increase in spontaneous excitatory synaptic activity that disappeared late during the TRH application. The duration of the inspiratory potentials was increased, indicating that the hypoglossal motoneurons received a longer duration synaptic input from the respiratory rhythm generator. 4. Type-1 inspiratory neurons showed a prolonged depolarization (3 cells), a transient depolarization (2 cells), or no change in membrane potential (2 cells) during 10 min of continued superfusion with a TRH-containing solution. The duration of the inspiratory potentials was increased during the TRH superfusion. With tetrodoxin (TTX, 1 microM) present in the superfusing solution TRH induced a prolonged depolarization (3 cells) or a transient depolarization (1 cell), demonstrating that type-1 inspiratory neurons are depolarized postsynaptically by TRH. The input resistance was not changed during the depolarizing response to TRH. 5. Type-2 inspiratory neurons showed a transient depolarization (7 cells) in response to bath-applied TRH. The duration of the inspiratory potentials was increased markedly during TRH. The transient depolarization was not the result of a postsynaptic action of TRH, because type-2 neurons (9 cells) showed no depolarization to TRH with TTX present in the superfusing solution. 6. Type-3 inspiratory neurons showed a transient depolarization (4 cells) with a partial recovery of the membrane potential late during the TRH application. The duration of the inspiratory potentials increased markedly during TRH. Four cells showed a transient depolarization with an increase in input resistance during TRH with TTX present in the superfusing solution. Thus type-3 neurons are depolarized postsynaptically by TRH. 7. We conclude that TRH increases the frequency of the respiratory rhythm in newborn mice through an action at the level of the brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Glucose sensing by GABAergic neurons in the mouse nucleus tractus solitarii

2015 ◽  
Vol 114 (2) ◽  
pp. 999-1007 ◽  
Author(s):  
Carie R. Boychuk ◽  
Peter Gyarmati ◽  
Hong Xu ◽  
Bret N. Smith
Keyword(s):  
Membrane Potential ◽  
Glucose Concentration ◽  
Blood Glucose Concentration ◽  
Glutamate Release ◽  
Glucose Sensing ◽  
Gabaergic Neurons ◽  
Nucleus Tractus Solitarii ◽  
Acid Decarboxylase ◽  
Action Potential Firing ◽  
Gaba Neurons

Changes in blood glucose concentration alter autonomic function in a manner consistent with altered neural activity in brain regions controlling digestive processes, including neurons in the brain stem nucleus tractus solitarii (NTS), which process viscerosensory information. With whole cell or on-cell patch-clamp recordings, responses to elevating glucose concentration from 2.5 to 15 mM were assessed in identified GABAergic NTS neurons in slices from transgenic mice that express EGFP in a subset of GABA neurons. Single-cell real-time RT-PCR was also performed to detect glutamic acid decarboxylase (GAD67) in recorded neurons. In most identified GABA neurons (73%), elevating glucose concentration from 2.5 to 15 mM resulted in either increased (40%) or decreased (33%) neuronal excitability, reflected by altered membrane potential and/or action potential firing. Effects on membrane potential were maintained when action potentials or fast synaptic inputs were blocked, suggesting direct glucose sensing by GABA neurons. Glucose-inhibited GABA neurons were found predominantly in the lateral NTS, whereas glucose-excited cells were mainly in the medial NTS, suggesting regional segregation of responses. Responses were prevented in the presence of glucosamine, a glucokinase (GCK) inhibitor. Depolarizing responses were prevented when KATP channel activity was blocked with tolbutamide. Whereas effects on synaptic input to identified GABAergic neurons were variable in GABA neurons, elevating glucose increased glutamate release subsequent to stimulation of tractus solitarius in unlabeled, unidentified neurons. These results indicate that GABAergic NTS neurons act as GCK-dependent glucose sensors in the vagal complex, providing a means of modulating central autonomic signals when glucose is elevated.

Neuronal Bursting Induced by NK3 Receptor Activation in the Neonatal Rat Spinal Cord In Vitro

2001 ◽  
Vol 86 (6) ◽  
pp. 2939-2950 ◽  
Author(s):  
Cristina Marchetti ◽  
Andrea Nistri
Keyword(s):  
Spinal Cord ◽  
Membrane Potential ◽  
Dorsal Root ◽  
Extracellular Recording ◽  
Rhythmic Activity ◽  
Input Resistance ◽  
Receptor Activation ◽  
Neonatal Rat ◽  
Rat Spinal Cord

Intracellular recording from lumbar motoneurons and extracellular recording from ventral roots of the neonatal rat isolated spinal cord were used to study the mechanisms responsible for the excitation mediated by NK3 tachykinin receptors. The selective NK3 agonists senktide or [MePhe7]neurokinin B induced a slow depolarization with superimposed oscillations (mean period ± SD was 2.8 ± 0.8 s) that, in the majority of cases, showed left-right alternation at segmental level and were synchronous between L2 and L5 of the same side. During agonist wash out (5–20 min) a delayed form of hyperexcitability emerged consisting of bursts lasting 8 ± 2 s (average interburst interval 55 ± 21 s) with superimposed oscillations usually with homosegmental alternation and heterosegmental synchronicity. Such bursting was accompanied by depression of GABAergic dorsal root potentials evoked by dorsal root stimulation and of the recurrent inhibitory postsynaptic potential recorded from motoneurons. Despite bursting, motoneuron membrane potential returned to baseline while input resistance was increased. Bursts were a network-dependent phenomenon triggered by previous NK3 receptor activation because bursting was suppressed by glutamate receptor antagonists and was insensitive to motoneuron membrane potential or subsequent application of an NK3 receptor antagonist. NK3 receptors operated synergistically with N-methyl-d-aspartate (NMDA) and 5-hydroxytryptamine (5-HT) to trigger fully alternating locomotor-like rhythms while NK3 receptor antagonism disrupted the same rhythm. In summary, in the neonatal rat spinal cord NK3 receptors could trigger rhythmic activity predominantly with alternation at segmental level but with synchronous coupling between ipsilateral motor pools. NK3receptor activation could also facilitate fictive locomotor patterns induced by NMDA and 5-HT.

scholarly journals Comparison of baroreceptive to other afferent synaptic transmission to the medial solitary tract nucleus

2008 ◽  
Vol 295 (5) ◽  
pp. H2032-H2042 ◽  
Author(s):  
Michael C. Andresen ◽  
James H. Peters
Keyword(s):  
Synaptic Transmission ◽  
Brain Stem ◽  
Glutamate Release ◽  
Second Order ◽  
Visceral Afferents ◽  
Solitary Tract Nucleus ◽  
Failure Rates ◽  
Solitary Tract ◽  
Frequency Dependent ◽  
Aortic Depressor Nerve

Cranial nerve visceral afferents enter the brain stem to synapse on neurons within the solitary tract nucleus (NTS). The broad heterogeneity of both visceral afferents and NTS neurons makes understanding afferent synaptic transmission particularly challenging. To study a specific subgroup of second-order neurons in medial NTS, we anterogradely labeled arterial baroreceptor afferents of the aortic depressor nerve (ADN) with lipophilic fluorescent tracer (i.e., ADN+) and measured synaptic responses to solitary tract (ST) activation recorded from dye-identified neurons in medial NTS in horizontal brain stem slices. Every ADN+ NTS neuron received constant-latency ST-evoked excitatory postsynaptic currents (EPSCs) (jitter <192 μs, SD of latency). Stimulus-recruitment profiles showed single thresholds and no suprathreshold recruitment, findings consistent with EPSCs arising from a single, branched afferent axon. Frequency-dependent depression of ADN+ EPSCs averaged ∼70% for five shocks at 50 Hz, but single-shock failure rates did not exceed 4%. Whether adjacent ADN− or those from unlabeled animals, other second-order NTS neurons (jitters <200 μs) had ST transmission properties indistinguishable from ADN+. Capsaicin (CAP; 100 nM) blocked ST transmission in some neurons. CAP-sensitive ST-EPSCs were smaller and failed over five times more frequently than CAP-resistant responses, whether ADN+ or from unlabeled animals. Variance-mean analysis of ST-EPSCs suggested uniformly high probabilities for quantal glutamate release across second-order neurons. While amplitude differences may reflect different numbers of contacts, higher frequency-dependent failure rates in CAP-sensitive ST-EPSCs may arise from subtype-specific differences in afferent axon properties. Thus afferent transmission within medial NTS differed by axon class (e.g., CAP sensitive) but was indistinguishable by source of axon (e.g., baroreceptor vs. nonbaroreceptor).

scholarly journals Astrocytic glutamate transporters reduce the neuronal and physiological influence of metabotropic glutamate receptors in nucleus tractus solitarii

2020 ◽  
Vol 318 (3) ◽  
pp. R545-R564 ◽  
Author(s):  
Diana Martinez ◽  
Richard C. Rogers ◽  
Gerlinda E. Hermann ◽  
Eileen M. Hasser ◽  
David D. Kline
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Glutamate Release ◽  
Synaptic Activity ◽  
Nucleus Tractus Solitarii ◽  
Substantial Contribution ◽  
Epsc Amplitude ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii

Astrocytic excitatory amino acid transporters (EAATs) are critical to restraining synaptic and neuronal activity in the nucleus tractus solitarii (nTS). Relief of nTS EAAT restraint generates two opposing effects, an increase in neuronal excitability that reduces blood pressure and breathing and an attenuation in afferent [tractus solitarius (TS)]-driven excitatory postsynaptic current (EPSC) amplitude. Although the former is due, in part, to activation of ionotropic glutamate receptors, there remains a substantial contribution from another unidentified glutamate receptor. In addition, the mechanism(s) by which EAAT inhibition reduced TS-EPSC amplitude is unknown. Metabotropic glutamate receptors (mGluRs) differentially modulate nTS excitability. Activation of group I mGluRs on nTS neuron somas leads to depolarization, whereas group II/III mGluRs on sensory afferents decrease TS-EPSC amplitude. Thus we hypothesize that EAATs control postsynaptic excitability and TS-EPSC amplitude via restraint of mGluR activation. To test this hypothesis, we used in vivo recording, brain slice electrophysiology, and imaging of glutamate release and TS-afferent Ca2+. Results show that EAAT blockade in the nTS with (3 S)-3-[[3-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methoxy]-l-aspartic acid (TFB-TBOA) induced group I mGluR-mediated depressor, bradycardic, and apneic responses that were accompanied by neuronal depolarization, elevated discharge, and increased spontaneous synaptic activity. Conversely, upon TS stimulation TFB-TBOA elevated extracellular glutamate to decrease presynaptic Ca2+ and TS-EPSC amplitude via activation of group II/III mGluRs. Together, these data suggest an important role of EAATs in restraining mGluR activation and overall cardiorespiratory function.

Effects of ouabain on background and voltage-dependent currents in canine colonic myocytes

1990 ◽  
Vol 259 (3) ◽  
pp. C402-C408 ◽  
Author(s):  
E. P. Burke ◽  
K. M. Sanders
Keyword(s):  
Membrane Potential ◽  
Potential Gradient ◽  
Circular Muscle ◽  
Input Resistance ◽  
Pump Current ◽  
Muscle Layer ◽  
Membrane Properties ◽  
Resting Potential ◽  
Voltage Dependent ◽  
In Cells

Previous studies have suggested that the membrane potential gradient across the circular muscle layer of the canine proximal colon is due to a gradient in the contribution of the Na(+)-K(+)-ATPase. Cells at the submucosal border generate approximately 35 mV of pump potential, whereas at the myenteric border the pump contributes very little to resting potential. Results from experiments in intact muscles in which the pump is blocked are somewhat difficult to interpret because of possible effects of pump inhibitors on membrane conductances. Therefore, we studied isolated colonic myocytes to test the effects of ouabain on passive membrane properties and voltage-dependent currents. Ouabain (10(-5) M) depolarized cells and decreased input resistance from 0.487 +/- 0.060 to 0.292 +/- 0.040 G omega. The decrease in resistance was attributed to an increase in K+ conductance. Studies were also performed to measure the ouabain-dependent current. At 37 degrees C, in cells dialyzed with 19 mM intracellular Na+ concentration [( Na+]i), ouabain caused an inward current averaging 71.06 +/- 7.49 pA, which was attributed to blockade of pump current. At 24 degrees C or in cells dialyzed with low [Na+]i (11 mM), ouabain caused little change in holding current. With the input resistance of colonic cells, pump current appears capable of generating at least 35 mV. Thus an electrogenic Na+ pump could contribute significantly to membrane potential.

Calmidazolium selectively inhibits exocytotic glutamate release evoked by P2X7 receptor activation

2012 ◽  
Vol 60 (8) ◽  
pp. 768-772 ◽  
Author(s):  
Chiara Cervetto ◽  
Maria Chiara Mazzotta ◽  
Daniela Frattaroli ◽  
Susanna Alloisio ◽  
Mario Nobile ◽  
...  
Keyword(s):  
P2x7 Receptor ◽  
Glutamate Release ◽  
Receptor Activation ◽  
P2x7 Receptor Activation
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