Modulation of Synaptic Transmission in the Rat Nucleus of the Solitary Tract by Endomorphin-1

2005 ◽  
Vol 93 (5) ◽  
pp. 2530-2540 ◽  
Author(s):  
Nicholas R. Glatzer ◽  
Bret N. Smith
Keyword(s):  
Synaptic Transmission ◽  
Opioid Receptors ◽  
Nucleus Tractus Solitarius ◽  
Integration Site ◽  
Brain Slices ◽  
Inhibitory Neurons ◽  
Solitary Tract ◽  
Endogenous Opioid ◽  
Opioid Agonist ◽  
Postsynaptic Currents

Activation of opioid receptors in the periphery and centrally in the brain results in inhibition of gastric and other vagally mediated functions. The aim of this study was to examine the role of the endogenous opioid agonist endomorphin 1 (EM-1) in regulating synaptic transmission within the nucleus tractus solitarius (NTS), an integration site for autonomic functions. We performed whole cell patch-clamp recordings from coronal brain slices of the rat medulla. A subset of the neurons studied was prelabeled with a stomach injection of the transsynaptic retrograde virus expressing EGFP, PRV-152. Solitary tract stimulation resulted in constant latency excitatory postsynaptic currents (EPSCs) that were decreased in amplitude by EM-1 (0.01–10 μM). The paired-pulse ratio was increased with little change in input resistance, suggesting a presynaptic mechanism. Spontaneous EPSCs were decreased in both frequency and amplitude by EM-1, and miniature EPSCs were reduced in frequency but not amplitude, suggesting a presynaptic mechanism for the effect. Spontaneous inhibitory postsynaptic currents (IPSCs) were also reduced in frequency by EM-1, but the effect was blocked by TTX, suggesting activity at receptors on the somata of local inhibitory neurons. Synaptic input arising from local NTS neurons, which were activated by focal photolysis of caged glutamate, was inhibited by EM-1. The actions of EM-1 were similar to those of d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) and were blocked by naltrexone, d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), or d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). These results suggest that EM-1 acts at μ-opioid receptors to modulate viscerosensory input and specific components of local synaptic circuitry in the NTS.

Dopamine Modulates Synaptic Transmission in the Nucleus of the Solitary Tract

2002 ◽  
Vol 88 (5) ◽  
pp. 2736-2744 ◽  
Author(s):  
David D. Kline ◽  
Kristin N. Takacs ◽  
Eckhard Ficker ◽  
Diana L. Kunze
Keyword(s):  
Synaptic Transmission ◽  
Nucleus Tractus Solitarius ◽  
Integration Site ◽  
Cell Voltage ◽  
Input Resistance ◽  
D2 Receptors ◽  
Synaptic Activity ◽  
Solitary Tract ◽  
Afferent Fibers ◽  
Sensory Fibers

10.1152/jn.00224.2002. Dopamine (DA) modulates the cardiorespiratory reflex by peripheral and central mechanisms. The aim of this study was to examine the role of DA in synaptic transmission of the nucleus tractus solitarius (NTS), the major integration site for cardiopulmonary reflexes. To examine DA's role, we used whole cell, voltage-clamp recordings in a rat horizontal brain stem slice. Solitary tract stimulation evoked excitatory postsynaptic currents (EPSCs) that were reduced to 70 ± 5% of control by DA (100 μM). The reduction in EPSCs by DA was accompanied by a decrease in the paired pulse depression ratio with little or no change in input resistance or EPSC decay, suggesting a presynaptic mechanism. The D1-like agonist SKF 38393 Br (30 μM) did not alter EPSC amplitude, whereas the D2-like agonist, quinpirole HCl (30 μM), depressed EPSCs to 73 ± 4% of control. The D2-like receptor antagonist, sulpiride (20 μM), abolished DA modulation of EPSCs. Most importantly, sulpiride alone increased EPSCs to 131 ± 10% of control, suggesting a tonic D2-like modulation of synaptic transmission in the NTS. Examination of spontaneous EPSCs revealed DA reversibly decreased the frequency of events from 9.4 ± 2.2 to 6.2 ± 1.4 Hz. Sulpiride, however, did not alter spontaneous events. Immunohistochemistry of NTS slices demonstrated that D2 receptors colocalized with synaptophysin and substance P, confirming a presynaptic distribution. D2 receptors also localized to cultured petrosal neurons, the soma of presynaptic afferent fibers. In the petrosal neurons, D2 was found in cells that were TH-immunopositive, suggesting they were chemoreceptor afferent fibers. These results demonstrate that DA tonically modulates synaptic activity between afferent sensory fibers and secondary relay neurons in the NTS via a presynaptic D2-like mechanism.

scholarly journals Isoflurane Differentially Modulates Inhibitory and Excitatory Synaptic Transmission to the Solitary Tract Nucleus

2008 ◽  
Vol 108 (4) ◽  
pp. 675-683 ◽  
Author(s):  
James H. Peters ◽  
Stuart J. McDougall ◽  
David Mendelowitz ◽  
Dennis R. Koop ◽  
Michael C. Andresen
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Second Order ◽  
Visceral Afferents ◽  
Gas Chromatography Mass Spectrometry ◽  
Gamma Aminobutyric Acid ◽  
Solitary Tract ◽  
Excitatory Postsynaptic Currents ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Presynaptic Mechanisms

Background Isoflurane anesthesia produces cardiovascular and respiratory depression, although the specific mechanisms are not fully understood. Cranial visceral afferents, which innervate the heart and lungs, synapse centrally onto neurons within the medial portion of the nucleus tractus solitarius (NTS). Isoflurane modulation of afferent to NTS synaptic communication may underlie compromised cardiorespiratory reflex function. Methods Adult rat hindbrain slice preparations containing the solitary tract (ST) and NTS were used. Shocks to ST afferents evoked excitatory postsynaptic currents with low-variability (SEM <200 mus) latencies identifying neurons as second order. ST-evoked and miniature excitatory postsynaptic currents as well as miniature inhibitory postsynaptic currents were measured during isoflurane exposure. Perfusion bath samples were taken in each experiment to measure isoflurane concentrations by gas chromatography-mass spectrometry. Results Isoflurane dose-dependently increased the decay-time constant of miniature inhibitory postsynaptic currents. At greater than 300 mum isoflurane, the amplitude of miniature inhibitory postsynaptic currents was decreased, but the frequency of events remained unaffected, whereas at equivalent isoflurane concentrations, the frequency of miniature excitatory postsynaptic currents was decreased. ST-evoked excitatory postsynaptic current amplitudes decreased without altering event kinetics. Isoflurane at greater than 300 mum increased the latency to onset and rate of synaptic failures of ST-evoked excitatory postsynaptic currents. Conclusions In second-order NTS neurons, isoflurane enhances phasic inhibitory transmission via postsynaptic gamma-aminobutyric acid type A receptors while suppressing excitatory transmission through presynaptic mechanisms. These results suggest that isoflurane acts through multiple distinct mechanisms to inhibit neurotransmission within the NTS, which would underlie suppression of homeostatic reflexes.

Ketamine Differentially Blocks Sensory Afferent Synaptic Transmission in Medial Nucleus Tractus Solitarius (mNTS)

2003 ◽  
Vol 98 (1) ◽  
pp. 121-132 ◽  
Author(s):  
Young-Ho Jin ◽  
Timothy W. Bailey ◽  
Mark W. Doyle ◽  
Bai-yan Li ◽  
Kyoung S. K. Chang ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Sensory Neurons ◽  
Action Potentials ◽  
Nucleus Tractus Solitarius ◽  
Solitary Tract ◽  
Medial Nucleus ◽  
Conduction Velocities ◽  
Autonomic Reflexes ◽  
Synaptic Failure ◽  
The Brain

Background Ketamine increases blood pressure and heart rate by unknown mechanisms, but studies suggest that an intact central nervous system and arterial baroreceptors are required. In the brain stem, medial nucleus tractus solitarius receives afferents from nodose neurons that initiate cardiovascular autonomic reflexes. Here, the authors assessed ketamine actions on afferent medial nucleus tractus solitarius synaptic transmission. Methods Ketamine was applied to horizontally sliced brain stems. Solitary tract (ST) stimulation evoked excitatory postsynaptic currents (eEPSCs) in medial nucleus tractus solitarius neurons. Capsaicin (200 nm) block of ST eEPSCs sorted neurons into sensitive (n = 19) and resistant (n = 23). In nodose ganglion slices, shocks to the peripheral vagal trunk activated afferent action potentials in sensory neurons classified by conduction velocities and capsaicin. Results Ketamine potently (10-100 mciro m) blocked small, ST-evoked -methyl-d-aspartate synaptic currents found only in a subset of capsaicin-resistant neurons (6 of 12). Surprisingly, ketamine reversibly inhibited ST eEPSC amplitudes and induced synaptic failure at lower concentrations in capsaicin-sensitive than in capsaicin-resistant neurons (P < 0.005; n = 11 and 11). Spontaneous EPSCs using non- -methyl-d-aspartate receptors were insensitive even to 1-3 mm ketamine, suggesting that ST responses were blocked presynaptically. Similarly, ketamine blocked C-type action potential conduction at lower concentrations than A-type nodose sensory neurons. Conclusion The authors conclude that ketamine inhibits postsynaptic -methyl-d-aspartate receptors and presynaptic afferent processes in medial nucleus tractus solitarius. Unexpectedly, capsaicin-sensitive (C-type), unmyelinated afferents are significantly more susceptible to block than capsaicin-resistant (A-type), myelinated afferents. This differentiation may be related to tetrodotoxin-resistant sodium currents. Since C-type afferents mediate powerful arterial baroreflexes effects, these differential actions may contribute to ketamine-induced cardiovascular dysfunction.

scholarly journals Opioid withdrawal abruptly disrupts amygdala circuit function by reducing peptide actions

2021 ◽  
Author(s):  
Gabrielle C Gregoriou ◽  
Sahil D Patel ◽  
Sebastian Pyne ◽  
Bryony L Winters ◽  
Elena E Bagley
Keyword(s):  
Drug Use ◽  
Synaptic Transmission ◽  
Basolateral Amygdala ◽  
Glutamate Release ◽  
Brain Slices ◽  
Opioid Withdrawal ◽  
Endogenous Opioids ◽  
Endogenous Opioid ◽  
Patch Clamp Electrophysiology ◽  
Dependent Learning

Opioid withdrawal drives relapse and contributes to compulsive drug use through disruption of endogenous opioid dependent learning circuits in the amygdala. Normally, endogenous opioids control these circuits by inhibiting glutamate release from basolateral amygdala principal neurons onto GABAergic intercalated cells. Using patch-clamp electrophysiology in rat brain slices, we reveal that opioid withdrawal dials down this endogenous opioid inhibition of synaptic transmission. Peptide activity is dialled down due to a protein kinase A dependent increase in the activity of the peptidase, neprilysin. This disrupts peptidergic control of both GABAergic and glutamatergic transmission through multiple amygdala circuits, including reward-related outputs to the nucleus accumbens. This likely disrupts peptide-dependent learning processes in the amygdala during withdrawal. and may direct behaviour towards compulsive drug use. Restoration of endogenous peptide activity during withdrawal may be a viable option to normalise synaptic transmission in the amygdala and restore normal reward learning.

scholarly journals The physiological modulation by intracellular kinases of hippocampal γ-oscillation in vitro

2020 ◽  
Vol 318 (5) ◽  
pp. C879-C888
Author(s):  
JianGang Wang ◽  
XiaHuan Gao ◽  
YaLi Wang ◽  
MengMeng Wang ◽  
ChunBo Ge ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Synaptic Transmission ◽  
Cell Voltage ◽  
Inhibitory Neurons ◽  
Akt Inhibitor ◽  
Postsynaptic Currents ◽  
Gamma Frequency ◽  
Dependent Protein ◽  
Amp Activated Protein Kinase

Hippocampal network oscillations at gamma frequency band (γ-oscillation, 20–80 Hz) are synchronized synaptic activities generated by the interactions between the excitatory and inhibitory interneurons and are associated with higher brain function such as learning and memory. Despite extensive studies about the modulation of intracellular kinases on synaptic transmission and plasticity, little is known about the effects of these kinases on γ-oscillations. In this study, we examined the effects of several critical intracellular kinases such as cyclic AMP-dependent protein kinase (PKA), protein kinase B (PKB)/Akt, protein kinase C (PKC), extracellular-regulated protein kinases (ERK) and AMP-activated protein kinase (AMPK), known to regulate synaptic transmission, on hippocampal γ-oscillations in vitro. We found that AMPK inhibitor but not PKA, PKC, or ERK inhibitor, strongly enhanced the power of γ-oscillation (γ-power) and that Akt inhibitor weakly increased γ-power. Western blot analysis confirmed that AMPK inhibitor reduced the expression of p-AMPK but not total AMPK. By using the slice whole cell voltage-clamp technique, we found that AMPK inhibitor increased the frequency but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSC) and had no effect on either frequency or amplitude of spontaneous excitatory postsynaptic currents (sEPSC). Therefore, AMPK activation negatively modulates hippocampal γ-oscillation via modulation of the inhibitory neurons.

Direct Actions of Cannabinoids on Synaptic Transmission in the Nucleus Accumbens: A Comparison With Opioids

2001 ◽  
Vol 85 (1) ◽  
pp. 72-83 ◽  
Author(s):  
Alexander F. Hoffman ◽  
Carl R. Lupica
Keyword(s):  
Nucleus Accumbens ◽  
Synaptic Transmission ◽  
Drugs Of Abuse ◽  
Glutamate Release ◽  
Brain Slices ◽  
Resting Membrane Potential ◽  
Projection Neurons ◽  
Whole Cell ◽  
Postsynaptic Currents ◽  
Abused Drugs

The nucleus accumbens (NAc) represents a critical site for the rewarding and addictive properties of several classes of abused drugs. The medium spiny GABAergic projection neurons (MSNs) in the NAc receive innervation from intrinsic GABAergic interneurons and glutamatergic innervation from extrinsic sources. Both GABA and glutamate release onto MSNs are inhibited by drugs of abuse, suggesting that this action may contribute to their rewarding properties. To investigate the actions of cannabinoids in the NAc, we performed whole cell recordings from MSNs located in the shell region in rat brain slices. The cannabinoid agonist WIN 55,212-2 (1 μM) had no effect on the resting membrane potential, input resistance, or whole cell conductance, suggesting no direct postsynaptic effects. Evoked glutamatergic excitatory postsynaptic currents (EPSCs) were inhibited to a much greater extent by [Tyr-d-Ala2, N-CH3-Phe4, Gly-ol-enkephalin] (DAMGO, ∼35%) than by WIN 55,212-2 (<20%), and an analysis of miniature EPSCs suggested that the effects of DAMGO were presynaptic, whereas those of WIN 55,212-2 were postsynaptic. However, electrically evoked GABAergic inhibitory postsynaptic currents (evIPSCs), were reduced by WIN 55,212-2 in every neuron tested (EC50 = 123 nM; 60% maximal inhibition), and the inhibition of IPSCs by WIN 55,212-2 was completely antagonized by the CB1 receptor antagonist SR141716A (1 μM). In contrast evIPSCs were inhibited in ∼50% of MSNs by the μ/δ opioid agonistd-Ala2-methionine2-enkephalinamide and were completely unaffected by a selective μ-opioid receptor agonist (DAMGO). WIN 55,212-2 also increased paired-pulse facilitation of the evIPSCs and did not alter the amplitudes of tetrodotoxin-resistant miniature IPSCs, suggesting a presynaptic action. Taken together, these data suggest that cannabinoids and opioids differentially modulate inhibitory and excitatory synaptic transmission in the NAc and that the abuse liability of marijuana may be related to the direct actions of cannabinoids in this structure.

Activation of δ-Opioid Receptors Excites Spinally Projecting Locus Coeruleus Neurons Through Inhibition of GABAergic Inputs

2002 ◽  
Vol 88 (5) ◽  
pp. 2675-2683 ◽  
Author(s):  
Yu-Zhen Pan ◽  
De-Pei Li ◽  
Shao-Rui Chen ◽  
Hui-Lin Pan
Keyword(s):  
Locus Coeruleus ◽  
Dorsal Horn ◽  
Opioid Receptors ◽  
Brain Slices ◽  
Gaba Release ◽  
Current Clamp ◽  
Excitatory Effect ◽  
Inhibitory System ◽  
Postsynaptic Currents

Stimulation of the noradrenergic nucleus locus coeruleus (LC) releases norepinephrine in the spinal cord, which inhibits dorsal horn neurons and produces analgesia. Activation of this descending noradrenergic pathway also contributes to the analgesic action produced by systemic opioids. The δ-opioid receptors are present presynaptically in the LC. However, their functional role in the control of the activity of spinally projecting LC neurons remains uncertain. In this study, we tested the hypothesis that activation of presynaptic δ-opioid receptors excites spinally projecting LC neurons through inhibition of GABA release. Spinally projecting LC neurons were retrogradely labeled by a fluorescent dye, DiI, injected into the spinal dorsal horn of rats. Whole cell voltage- and current-clamp recordings were performed on DiI-labeled LC neurons in brain slices in vitro. Retrogradely labeled LC noradrenergic neurons were demonstrated by dopamine-β-hydroxylase immunofluorescence. [d-Pen2,d-Pen5]-enkephalin (DPDPE, 1 μM) significantly decreased the frequency of GABA-mediated miniature inhibitory postsynaptic currents (IPSCs) of nine DiI-labeled LC neurons from 2.1 ± 0.5 to 0.7 ± 0.2 Hz without altering their amplitude and the kinetics. On the other hand, the miniature excitatory postsynaptic currents (EPSC) of nine DiI-labeled LC neurons were not significantly altered by DPDPE. Furthermore, DPDPE significantly inhibited the amplitude of evoked IPSC but not EPSC in eight DiI-labeled LC neurons. Under the current-clamp condition, the firing activity in 9 of 11 DiI-labeled LC neurons was significantly increased by 1 μM DPDPE from 4.6 ± 0.7 to 6.2 ± 1.0 Hz. Bicuculline (20 μM) also significantly increased the firing frequency in 13 of 20 neurons from 1.8 ± 0.5 to 2.8 ± 0.6 Hz. Additionally, the excitatory effect of DPDPE on LC neurons was diminished in the presence of bicuculline. Collectively, these data strongly suggest that activation of presynaptic δ-opioid receptors by DPDPE excites a population of spinally projecting LC neurons by preferential inhibition of GABA release. Thus presynaptic δ-opioid receptors likely play an important role in the regulation of the excitability of spinally projecting LC neurons and the descending noradrenergic inhibitory system.

Postnatal Development of Inhibitory Synaptic Transmission in the Rostral Nucleus of the Solitary Tract

2001 ◽  
Vol 85 (5) ◽  
pp. 2203-2212 ◽  
Author(s):  
Gintautas Grabauskas ◽  
Robert M. Bradley
Keyword(s):  
Synaptic Transmission ◽  
Postnatal Development ◽  
Age Groups ◽  
Brain Slices ◽  
Single Stimulus ◽  
Synaptic Activity ◽  
Membrane Properties ◽  
Tetanic Stimulation ◽  
Solitary Tract ◽  
Inhibitory Synaptic Transmission

To explore the postnatal development of inhibitory synaptic activity in the rostral (gustatory) nucleus of the solitary tract (rNST), whole cell and gramicidin perforated patch-clamp recordings were made in five age groups of rats [ postnatal day 0–7 ( P0–7), P8–14, P15–21, P22–30, and P > 55]. The passive membrane properties of the developing rNST neurons as well as the electrophysiological and pharmacological characteristics of single and tetanic stimulus-evoked inhibitory postsynaptic potentials (IPSPs) were studied in brain slices under glutamate receptor blockade. During the first postnatal weeks, significant changes in resting membrane potential, spontaneous activity, input resistance, and neuron membrane time constant of the rNST neurons occurred. Although all the IPSPs recorded were hyperpolarizing, the rise and decay time constants of the single stimulus shock-evoked IPSPs decreased, and the inhibition response–concentration function to the γ-aminobutyric acid (GABA) receptor antagonist bicuculline methiodide (BMI) shifted to the left during development. In P0–7 and P8–14, but not in older animals, the IPSPs had a BMI-insensitive component that was sensitive to block by picrotoxin, suggesting a transient expression of GABAC receptors. Tetanic stimulation resulted in both short- and long-term changes of inhibitory synaptic transmission in the rNST. For P0–7 and P8–14 animals tetanic stimulation resulted in a sustained hyperpolarization that was maintained for some time after termination of the tetanic stimulation. In contrast, tetanic stimulation of neurons in P15–21 and older animals resulted in hyperpolarization that was not sustained but decayed back to a more positive level with an exponential time course. Tetanic stimulation resulted in potentiation of single stimulus shock-evoked IPSPs in ∼50% of neurons in all age groups. These developmental changes in inhibitory synaptic transmission in the rNST may play an important role in shaping synaptic activity in early development of the rat gustatory system during a time of maturation of taste preferences and aversions.

scholarly journals GPI-1046 Increases Presenilin-1 Expression and Restores NMDA Channel Activity

2010 ◽  
Vol 37 (4) ◽  
pp. 457-467 ◽  
Author(s):  
Joseph P. Steiner ◽  
Kathryn B. Payne ◽  
Christopher Drummond Main ◽  
Sabrina D'Alfonso ◽  
Kirsten X. Jacobsen ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Synaptic Transmission ◽  
Brain Slices ◽  
Synaptic Activity ◽  
Presenilin 1 ◽  
Receptor Function ◽  
Channel Function ◽  
Nmda Channel ◽  
Nmda Receptor Function ◽  
6 Hydroxydopamine

Background:Previously we showed that 6-hydroxydopamine lesions of the substantia nigra eliminate corticostriatal LTP and that the neuroimmunolophilin ligand (NIL), GPI-1046, restores LTP.Methods:We used cDNA microarrays to determine what mRNAs may be over- or under-expressed in response to lesioning and/or GPI-1046 treatment. Patch clamp recordings were performed to investigate changes in NMDA channel function before and after treatments.Results:We found that 51 gene products were differentially expressed. Among these we found that GPI-1046 treatment up-regulated presenilin-1 (PS-1) mRNA abundance. This finding was confirmed using QPCR. PS-1 protein was also shown to be over-expressed in the striatum of lesioned/GPI-1046-treated rats. As PS-1 has been implicated in controlling NMDA-receptor function and LTP is reduced by lesioning we assayed NMDA mediated synaptic activity in striatal brain slices. The lesion-induced reduction of dopaminergic innervation was accompanied by the near complete loss of NDMA receptor-mediated synaptic transmission between the cortex and striatum. GPI-1046 treatment of the lesioned rats restored NMDA-mediated synaptic transmission but not the dopaminergic innervation. Restoration of NDMA channel function was apparently specific as the sodium channel current density was also reduced due to lesioning but GPI-1046 did not reverse this effect. We also found that restoration of NMDA receptor function was also not associated with either an increase in NMDA receptor mRNA or protein expression.Conclusion:As it has been previously shown that PS-1 is critical for normal NMDA receptor function, our data suggest that the improvement of excitatory neurotransmission occurs through the GPI-1046-induced up-regulation of PS-1.

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