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.

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.

Possible nicotinic receptor-mediated modulation of synaptic transmission in nucleus of the solitary tract

1997 ◽  
Vol 272 (3) ◽  
pp. R869-R873
Author(s):  
T. Shiraki ◽  
A. Toyoda ◽  
H. Sugino ◽  
A. Hori ◽  
S. Kobayashi
Keyword(s):  
Synaptic Transmission ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Single Channel ◽  
Signal Transmission ◽  
Neuronal Cell ◽  
Cell Voltage ◽  
Extracellular Potassium ◽  
Solitary Tract ◽  
Single Channel Currents

Signal transmission from afferent nerves to neurons in the nucleus of the solitary tract (NTS) may be mediated partially by nicotinic acetylcholine receptors (nAChRs). Here, we investigated nAChR-mediated signal transmission using rat NTS slices. First, we characterized nAChRs by obtaining patch-clamp recordings from NTS neuronal cell bodies. Under whole cell voltage-clamp conditions at -60 mV, application of nicotine induced an inward current, and this effect was blocked by hexamethonium. In outside-out patch recordings, nicotine was seen to induce a hexamethonium-sensitive single-channel current. Second, we investigated nAChR-mediated signal transmission. Fast synaptic transmission mediated by nAChRs was not detected. The action of diffusible acetylcholine (ACh) on nAChRs was then tested using the outside-out patches excised from NTS neurons as probes for ACh. When the patch was placed at a distance of 20-30 microm from the cell body, single-channel currents were recorded, and these were inhibited by hexamethonium. The frequency of channel opening was increased by high-extracellular potassium concentration solution suggesting the voltage-dependent release ofACh that acts on nAChRs. These results suggested that nAChR-mediated signal transmission from sensory afferents to NTS neurons is in part mediated by diffusible ACh.

Presynaptic or postsynaptic location of receptors for angiotensin II and substance P in the medial solitary tract nucleus

1996 ◽  
Vol 75 (6) ◽  
pp. 2220-2228 ◽  
Author(s):  
L. Qu ◽  
A. J. McQueeney ◽  
K. L. Barnes
Keyword(s):  
Substance P ◽  
Synaptic Transmission ◽  
Firing Rate ◽  
Cardiovascular Effects ◽  
Ang Ii ◽  
Solitary Tract ◽  
Medial Nucleus ◽  
Afferent Fibers ◽  
Before And After ◽  
Dorsal Medulla

1. Microinjection of angiotensin (Ang) II or substance P (SP) into the medial nucleus tractus solitarii (nTS) produces similar decreases in arterial pressure and heart rate. We previously reported that some medial nTS neurons responsive to SP were also excited by Ang II, and that Ang II increased the release of SP from medulla slices. Both electrophysiological and anatomic data suggest that the cardiovascular effects of these peptides may be mediated by a common neuronal pathway consisting of SP-containing vagal afferent fibers with presynaptic Ang II receptors that innervate medial nTS neurons with SP receptors. To evaluate the validity of this model, we established the presynaptic or postsynaptic location of the receptors for Ang II and SP that mediate excitation of medial nTS neurons by determining the capacity of each peptide to activate the cell before and after blocking synaptic transmission in rat dorsal medulla slices. 2. Extracellular recordings were obtained from 55 medial nTS neurons responsive to Ang II or SP in 400-microns horizontal slices of the dorsal medulla. Neuronal excitation by Ang II and SP was tested before, during, and after reversal of synaptic blockade with low-Ca2+ (0.2 mM), high Mg2+ (5 mM) artificial cerebrospinal fluid (aCSF). Elimination of synaptically evoked short latency responses of the neuron to current pulses applied to afferent fibers in the solitary tract (TS) documented blockade of synaptic transmission by low-Ca2+ aCSF. In most cases, the basal firing rate of the cell increased slowly during perfusion with low-Ca2+ aCSF and stabilized after approximately 30 min at a higher level of spontaneous activity. Responses to the peptides and TS stimulation were also documented after synaptic blockade had been reversed by adding aCSF containing 2-mM Ca2+. 3. Of the 55 medial nTS neurons, 41 were responsive to Ang II; whereas, 50 of the 55 cells were responsive to SP. The neurons were divided into three subgroups on the basis of their responsiveness to Ang II and SP. Although most neurons were responsive to both Ang II and SP (n = 36), five other cells were excited only by Ang II, and 14 neurons were activated only by SP. Of the 55 neurons, 26 were also responsive to L-glutamate: 14 of 17 cells responsive to both Ang II and SP, all 5 neurons excited by Ang II but not by SP, and 7 of 10 neurons responsive only to SP were also excited by L-glutamate. The latency of the action potentials evoked by TS stimulation was much shorter in those neurons responsive only to Ang II (3.6 ms) than in cells excited by both Ang II and SP (6.8 ms) or responsive only to SP (7.4 ms). 4. In 21 of the 36 medial nTS neurons responsive to both Ang II and SP, Ang II continued to excite the cell when synaptic responses to TS stimulation were prevented by low-Ca2+ aCSF, but had no effect on the firing rate of the other 15 neurons during synaptic blockade. Excitation induced by Ang II was also prevented in two of the five medial nTS neurons responsive only to Ang II when synaptic transmission in the slice was blocked. Low-Ca2+ aCSF failed to prevent excitation by SP or L-glutamate in all medial nTS cells responsive to these agonists (n = 50 and n = 26, respectively). In contrast to these observations in medial nTS neurons, Ang II-induced excitation was not altered during synaptic blockade in any of the six dmnX cells studied. No responses to SP or L-glutamate were blocked in dmnX neurons, as also seen in the medial nTS. 5. When all medial nTS neurons responsive to Ang II were examined, the latencies of the response to TS stimulation were significantly shorter in those neurons with presynaptic Ang II receptors than in the group of cells with postsynaptic receptors. In addition, neurons with presynaptic Ang II receptors were distributed differently within the medial nTS than cells with postsynaptic Ang II receptors.(ABSTRACT TRUNCATED)

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.

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.

Cannabinoids modulate spontaneous synaptic activity in retinal ganglion cells

2011 ◽  
Vol 28 (5) ◽  
pp. 393-402 ◽  
Author(s):  
T. P. MIDDLETON ◽  
D. A. PROTTI
Keyword(s):  
Synaptic Transmission ◽  
Retinal Ganglion Cells ◽  
Cannabinoid Receptor ◽  
Ganglion Cells ◽  
Cell Voltage ◽  
Receptor Activation ◽  
Synaptic Activity ◽  
Retinal Cell ◽  
Retinal Ganglion ◽  
Retinal Processing

AbstractThe endocannabinoid (ECB) system has been found throughout the central nervous system and modulates cell excitability in various forms of short-term plasticity. ECBs and their receptors have also been localized to all retinal cells, and cannabinoid receptor activation has been shown to alter voltage-dependent conductances in several different retinal cell types, suggesting a possible role for cannabinoids in retinal processing. Their effects on synaptic transmission in the mammalian retina, however, have not been previously investigated. Here, we show that exogenous cannabinoids alter spontaneous synaptic transmission onto retinal ganglion cells (RGCs). Using whole-cell voltage-clamp recordings in whole-mount retinas, we measured spontaneous postsynaptic currents (SPSCs) in RGCs in adult and young (P14–P21) mice. We found that the addition of an exogenous cannabinoid agonist, WIN55212-2 (5 μM), caused a significant reversible reduction in the frequency of SPSCs. This change, however, did not alter the kinetics of the SPSCs, indicating a presynaptic locus of action. Using blockers to isolate inhibitory or excitatory currents, we found that cannabinoids significantly reduced the release probability of both GABA and glutamate, respectively. While the addition of cannabinoids reduced the frequency of both GABAergic and glutamatergic SPSCs in both young and adult mice, we found that the largest effect was on GABA-mediated currents in young mice. These results suggest that the ECB system may potentially be involved in the modulation of signal transmission in the retina. Furthermore, they suggest that it might play a role in the developmental maturation of synaptic circuits, and that exogenous cannabinoids are likely able to disrupt retinal processing and consequently alter vision.

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.

scholarly journals NMDA Receptor-Dependent Synaptic Activity in Dorsal Motor Nucleus of Vagus Mediates the Enhancement of Gastric Motility by Stimulating ST36

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Xinyan Gao ◽  
Yongfa Qiao ◽  
Baohui Jia ◽  
Xianghong Jing ◽  
Bin Cheng ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Gastric Motility ◽  
Low Frequency ◽  
Synaptic Activity ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Vagal Reflex ◽  
Precise Molecular Mechanism ◽  
Lines Of Evidence

Previous studies have demonstrated the efficacy of electroacupuncture at ST36 for patients with gastrointestinal motility disorders. While several lines of evidence suggest that the effect may involve vagal reflex, the precise molecular mechanism underlying this process still remains unclear. Here we report that the intragastric pressure increase induced by low frequency electric stimulation at ST36 was blocked by AP-5, an antagonist of N-methyl-D-aspartate receptors (NMDARs). Indeed, stimulating ST36 enhanced NMDAR-mediated, but not 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic-acid-(AMPA-) receptor-(AMPAR-) mediated synaptic transmission in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). We also identified that suppression of presynapticμ-opioid receptors may contribute to upregulation of NMDAR-mediated synaptic transmission induced by electroacupuncture at ST36. Furthermore, we determined that the glutamate-receptor-2a-(NR2A-) containing NMDARs are essential for NMDAR-mediated enhancement of gastric motility caused by stimulating ST36. Taken together, our results reveal an important role of NMDA receptors in mediating enhancement of gastric motility induced by stimulating ST36.

Sign in / Sign up

Export Citation Format

Share Document