scholarly journals Prostaglandin E2 depresses solitary tract-mediated synaptic transmission in the nucleus tractus solitarius

Neuroscience ◽  
2007 ◽  
Vol 146 (2) ◽  
pp. 792-801 ◽  
Author(s):  
N. Laaris ◽  
D. Weinreich
2002 ◽  
Vol 88 (5) ◽  
pp. 2736-2744 ◽  
Author(s):  
David D. Kline ◽  
Kristin N. Takacs ◽  
Eckhard Ficker ◽  
Diana L. Kunze

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.


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 ◽  
...  

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.


2005 ◽  
Vol 93 (5) ◽  
pp. 2530-2540 ◽  
Author(s):  
Nicholas R. Glatzer ◽  
Bret N. Smith

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.


1997 ◽  
Vol 78 (1) ◽  
pp. 82-91 ◽  
Author(s):  
Stefan Titz ◽  
Bernhard U. Keller

Titz, Stefan and Bernhard U. Keller. Rapidly deactivating AMPA receptors determine excitatory synaptic transmission to interneurons in the nucleus tractus solitarius from rat. J. Neurophysiol. 78: 82–91, 1997. Excitatory synaptic transmission was investigated in interneurons of the parvocellular nucleus tractus solitarius (pNTS) by performing patch-clamp experiments in thin slice preparations from rat brain stem. Stimulation of single afferent fibers evoked excitatory postsynaptic currents (EPSCs) mediated by glutamate receptors of the dl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) and N-methyl-d-aspartate types. AMPA-receptor-mediated EPSCs displayed decay time constants of 3.5 ± 1.2 (SD) ms (13 cells), which were slow compared with EPSC decay time constants in neurons of the cerebellum or hippocampus. Slow EPSC decay was not explained by dendritic filtering, because the passive membrane properties of pNTS interneurons provided favorable voltage-clamp conditions. Also, the slowness of EPSC decay did not result from slow deactivation of AMPA receptors (0.7 ± 0.2 ms, 5 cells), which was investigated during rapid application of agonist to outside-out patches. Comparison of AMPA receptor kinetics with EPSC decay time constants suggested that the slow time course of EPSCs resulted from the prolonged presence of glutamate in the synaptic cleft.


2008 ◽  
Vol 108 (4) ◽  
pp. 675-683 ◽  
Author(s):  
James H. Peters ◽  
Stuart J. McDougall ◽  
David Mendelowitz ◽  
Dennis R. Koop ◽  
Michael C. Andresen

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.


1995 ◽  
Vol 74 (4) ◽  
pp. 1518-1528 ◽  
Author(s):  
M. C. Andresen ◽  
M. Yang

1. Synaptic responses of medial nucleus tractus solitarius (mNTS) neurons to solitary tract (ST) activation were studied in a horizontal brain slice preparation of the rat medulla. Slices included sections of ST sufficiently long that the ST could be electrically activated several millimeters from the recording site of cell bodies in mNTS. 2. Three types of synaptic events were evoked in response to ST stimulation: simple excitatory postsynaptic potentials (EPSPs), simple inhibitory postsynaptic potentials (IPSPs), and complex EPSP-IPSP sequences. Simple EPSPs had substantially shorter latencies than IPSPs (3.39 +/- 0.65 ms, mean +/- SE, n = 42, vs. 5.86 +/- 0.71 ms, n = 6, respectively). 3. EPSP amplitude increased linearly with increasing hyperpolarization, with an extrapolated reversal potential near 0 mV. 4. EPSPs were maximal at < 0.5 Hz of sustained, constant-frequency ST stimulation (n = 14). EPSP amplitude declined to an average of 57.5% of control at 10 Hz after 2 s of sustained stimulation. With 1 min of sustained, 100-Hz stimulation, EPSP amplitude declined to near zero. 5. With stimuli intermittently delivered as 100-ms bursts every 300 ms, generally comparable average EPSPs were evoked during constant and burst patterns of ST stimulation. The amplitude of the initial EPSP in each burst was very well maintained even at intraburst stimulation rates of 100 Hz. 6. At resting membrane potentials, low constant frequencies of ST stimulation (< 5 Hz) reliably elicited action potentials and suppressed spontaneous spiking, but higher frequencies led to spike failures (> 85% at 100 Hz). Between 5 and 10 Hz, this periodic stimulation-suppression cycle clearly entrained action potential activity to the ST stimuli. Similar patterns of current pulses (5 ms) reliably evoked action potentials with each pulse to higher frequencies (50 Hz) without failures, and entrainment was similar to ST stimulation. 7. In a subset of nucleus tractus solitarius (NTS) neurons (3 of 9 studied), bursts of ST stimuli were as much as 50% more effective at transmitting high frequencies (> 10 Hz) of ST stimulation than the equivalent constant frequencies (P < 0.0001). 8. The long-latency simple IPSPs with no preceding EPSPs reversed to become depolarizing at potentials more negative than -62.9 +/- 7.0 mV (n = 5) and were blocked by the non-N-methyl-D-aspartate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (n = 3). The ST stimulation frequency-response relation of these IPSPs was similar to that for the short-latency EPSP response excited by ST synapses. Thus these IPSPs appear to be activated polysynaptically via a glutamatergic-GABAergic sequence in response to ST activation. 9. The results suggest that sensory afferent synapses in mNTS have limited transmission of high-frequency inputs. Both synaptic transmission and the characteristics of the postsynaptic neuron importantly contribute to the action potential transmission from afferent to NTS neuron and beyond. This overall frequency response limitation may contribute to the accommodation of reflex responses from sensory afferent inputs such as arterial baroreceptors within their physiological discharge frequency range.


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