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

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.

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Homeostatic Plasticity Hypothesis and Mechanisms of Neocortical Epilepsies

Epilepsy Currents ◽

10.1111/j.1535-7511.2005.00042.x ◽

2005 ◽

Vol 5 (4) ◽

pp. 133-135 ◽

Cited By ~ 1

Author(s):

Jaideep Kapur ◽

Stacey Trotter

Keyword(s):

Synaptic Plasticity ◽

Neuronal Activity ◽

Pyramidal Neurons ◽

Pyramidal Cells ◽

Homeostatic Plasticity ◽

Excitatory Synapses ◽

Excitatory Postsynaptic Currents ◽

Inhibitory Postsynaptic Currents ◽

Postsynaptic Currents ◽

Homeostatic Synaptic Plasticity

Homeostatic Synaptic Plasticity Can Explain Posttraumatic Epileptogenesis in Chronically Isolated Neocortex Houweling AR, Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ Cereb Cortex 2004 [Epub ahead of print] Permanently isolated neocortex develops chronic hyperexcitability and focal epileptogenesis in a period of days to weeks. The mechanisms operating in this model of posttraumatic epileptogenesis are not well understood. We hypothesized that the spontaneous burst discharges recorded in permanently isolated neocortex result from homeostatic plasticity (a mechanism generally assumed to stabilize neuronal activity) induced by low neuronal activity after deafferentation. To test this hypothesis, we constructed computer models of neocortex incorporating a biologically based homeostatic plasticity rule that operates to maintain firing rates. After deafferentation, homeostatic upregulation of excitatory synapses on pyramidal cells, either with or without concurrent downregulation of inhibitory synapses or upregulation of intrinsic excitability, initiated slowly repeating burst discharges that closely resembled the epileptiform burst discharges recorded in permanently isolated neocortex. These burst discharges lasted a few hundred milliseconds, propagated at 1 to 3 cm/s and consisted of large (10–15 mV) intracellular depolarizations topped by a small number of action potentials. Our results support a role for homeostatic synaptic plasticity as a novel mechanism of posttraumatic epileptogenesis. Excitatory and Inhibitory Postsynaptic Currents in a Rat Model of Epileptogenic Microgyria Jacobs KM, Prince DA J Neurophysiol 2005;93:687–696 Developmental cortical malformations are common in patients with intractable epilepsy; however, mechanisms contributing to this epileptogenesis are currently poorly understood. We previously characterized hyperexcitability in a rat model that mimics the histopathology of human four-layered microgyria. Here we examined inhibitory and excitatory postsynaptic currents in this model to identify functional alterations that might contribute to epileptogenesis associated with microgyria. We recorded isolated whole-cell excitatory postsynaptic currents and GABAA receptor–mediated inhibitory currents from layer V pyramidal neurons in the region previously shown to be epileptogenic (paramicrogyral area) and in homotopic control cortex. Epileptiform-like activity could be evoked in 60% of paramicrogyral (PMG) cells by local stimulation. The peak conductance of both spontaneous and evoked inhibitory postsynaptic currents was significantly larger in all PMG cells compared with controls. This difference in amplitude was not present after blockade of ionotropic glutamatergic currents or for miniature (m) inhibitory postsynaptic currents, suggesting that it was due to the excitatory afferent activity driving inhibitory neurons. This conclusion was supported by the finding that glutamatereceptor antagonist application resulted in a significantly greater reduction in spontaneous inhibitory postsynaptic current frequency in one PMG cell group (PMGE) compared with control cells. The frequency of both spontaneous and miniature excitatory postsynaptic currents was significantly greater in all PMG cells, suggesting that pyramidal neurons adjacent to a microgyrus receive more excitatory input than do those in control cortex. These findings suggest that there is an increase in numbers of functional excitatory synapses on both interneurons and pyramidal cells in the PMG cortex, perhaps due to hyperinnervation by cortical afferents originally destined for the microgyrus proper.

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Cortical potentiation induced by calcitonin gene-related peptide (CGRP) in the insular cortex of adult mice

10.21203/rs.2.22676/v2 ◽

2020 ◽

Author(s):

Yinlu Liu ◽

Qi-Yu Chen ◽

Jung Hyun Lee ◽

Xu-Hui Li ◽

Shengyuan Yu ◽

...

Keyword(s):

Insular Cortex ◽

Calcitonin Gene Related Peptide ◽

Anterior Cingulate ◽

Excitatory Postsynaptic Currents ◽

Postsynaptic Currents ◽

Related Peptide ◽

Excitatory Transmission ◽

Bath Application ◽

Calcitonin Gene ◽

Presynaptic Mechanisms

Abstract Recent studies demonstrate that calcitonin gene-related peptide (CGRP) plays critical roles in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP and its receptors are expressed in cortical areas that are critical for pain perception including the anterior cingulate cortex (ACC) and insular cortex (IC). Recent studies reported that CGRP enhanced excitatory transmission in the ACC. However, little is known about the possible effect of CGRP on excitatory transmission in the IC. In the present study, we investigated the role of CGRP on synaptic transmission in the IC slices of adult male mice. Bath application of CGRP produced dose-dependent potentiation of evoked excitatory postsynaptic currents (eEPSCs). This potentiation was NMDA receptor (NMDAR) independent. After application of CGRP1 receptor antagonist CGRP8-37 or BIBN 4096, CGRP produced potentiation was significantly reduced. Paired-pulse facilitation was significantly decreased by CGRP, suggesting possible presynaptic mechanisms. Consistently, bath application of CGRP significantly increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs). By contrast, amplitudes of sEPSCs and mEPSCs were not significantly affected. Finally, adenylyl cyclase subtype 1 (AC1) and protein kinase A (PKA) are critical for CGRP-produced potentiation, since both selective AC1 inhibitor NB001 and the PKA inhibitor KT5720 completely blocked the potentiation. Our results provide direct evidence that CGRP contributes to synaptic potentiation in the IC, and the AC1 inhibitor NB001 may be beneficial for the treatment of migraine in the future.

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Actions of Midazolam on Excitatory Transmission in Dorsal Horn Neurons of Adult Rat Spinal Cord

Anesthesiology ◽

10.1097/00000542-200602000-00020 ◽

2006 ◽

Vol 104 (2) ◽

pp. 338-343 ◽

Cited By ~ 33

Author(s):

Tatsuro Kohno ◽

Ayako Wakai ◽

Toyofumi Ataka ◽

Miho Ikoma ◽

Tomohiro Yamakura ◽

...

Keyword(s):

Spinal Cord ◽

Dorsal Horn ◽

Benzodiazepine Receptor ◽

Gamma Aminobutyric Acid ◽

Excitatory Postsynaptic Currents ◽

Adult Rat ◽

Dorsal Horn Neurons ◽

Postsynaptic Currents ◽

Excitatory Transmission ◽

Adult Rat Spinal Cord

Background Although intrathecal administration of midazolam, a water-soluble imidazobenzodiazepine derivative, has been found to produce analgesia, how it exerts this effect at the neuronal level in the spinal cord is not fully understood. Methods The effects of midazolam on electrically evoked and spontaneous excitatory transmission were examined in lamina II neurons of adult rat spinal cord slices using the whole cell patch clamp technique. Results Bath-applied midazolam (1 microm) diminished Adelta- and C-fiber evoked polysynaptic excitatory postsynaptic currents in both amplitude and integrated area. However, it affected neither Adelta- and C-fiber evoked monosynaptic excitatory postsynaptic currents in amplitude nor miniature excitatory postsynaptic currents in amplitude, frequency, and decay time constant. In the presence of a benzodiazepine receptor antagonist, flumazenil (5 microm), midazolam (1 microm) did not diminish Adelta-fiber evoked polysynaptic excitatory postsynaptic currents, suggesting that midazolam modulate the gamma-aminobutyric acid interneurons in the dorsal horn. Conclusions Midazolam reduced excitatory synaptic transmission by acting on the gamma-aminobutyric acid type A/benzodiazepine receptor in interneurons, leading to a decrease in the excitability of spinal dorsal horn neurons. This may be a possible mechanism for the antinociception by midazolam in the spinal cord.

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High Ratio of Synaptic Excitation to Synaptic Inhibition in Hilar Ectopic Granule Cells of Pilocarpine-Treated Rats

Journal of Neurophysiology ◽

10.1152/jn.00663.2010 ◽

2010 ◽

Vol 104 (6) ◽

pp. 3293-3304 ◽

Cited By ~ 41

Author(s):

Ren-Zhi Zhan ◽

Olga Timofeeva ◽

J. Victor Nadler

Keyword(s):

Status Epilepticus ◽

Granule Cell ◽

Granule Cells ◽

Mossy Fiber ◽

High Ratio ◽

Synaptic Function ◽

Excitatory Postsynaptic Currents ◽

Inhibitory Postsynaptic Currents ◽

Synaptic Excitation ◽

Postsynaptic Currents

After experimental status epilepticus, many dentate granule cells born into the postseizure environment migrate aberrantly into the dentate hilus. Hilar ectopic granule cells (HEGCs) have also been found in persons with epilepsy. These cells exhibit a high rate of spontaneous activity, which may enhance seizure propagation. Electron microscopic studies indicated that HEGCs receive more recurrent mossy fiber innervation than normotopic granule cells in the same animals but receive much less inhibitory innervation. This study used hippocampal slices prepared from rats that had experienced pilocarpine-induced status epilepticus to test the hypothesis that an imbalance of synaptic excitation and inhibition contributes to the hyperexcitability of HEGCs. Mossy fiber stimulation evoked a much smaller GABAA receptor–mediated inhibitory postsynaptic currents (IPSC) in HEGCs than in normotopic granule cells from either control rats or rats that had experienced status epilepticus. However, recurrent mossy fiber-evoked excitatory postsynaptic currents (EPSCs) of similar size were recorded from HEGCs and normotopic granule cells in status epilepticus–experienced rats. HEGCs exhibited the highest frequency of miniature excitatory postsynaptic currents (mEPSCs) and the lowest frequency of miniature inhibitory postsynaptic currents (mIPSCs) of any granule cell group. On average, both mEPSCs and mIPSCs were of higher amplitude, transferred more charge per event, and exhibited slower kinetics in HEGCs than in granule cells from control rats. Charge transfer per unit time in HEGCs was greater for mEPSCs and much less for mIPSCs than in the normotopic granule cell groups. A high ratio of excitatory to inhibitory synaptic function probably accounts, in part, for the hyperexcitability of HEGCs.

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Adrenoreceptor modulation of oromotor pathways in the rat medulla

Journal of Neurophysiology ◽

10.1152/jn.00091.2014 ◽

2014 ◽

Vol 112 (3) ◽

pp. 580-593 ◽

Cited By ~ 8

Author(s):

Jason S. Nasse ◽

Joseph B. Travers

Keyword(s):

Patch Clamp ◽

Calcium Imaging ◽

Solitary Tract ◽

Noradrenergic Neurons ◽

Medullary Reticular Formation ◽

Inward Current ◽

Postsynaptic Currents ◽

Presynaptic Mechanisms ◽

Reticular Neurons ◽

Patch Clamp Electrophysiology

Regulation of feeding behavior involves the integration of multiple physiological and neurological pathways that control both nutrient-seeking and consummatory behaviors. The consummatory phase of ingestion includes stereotyped oromotor movements of the tongue and jaw that are controlled through brain stem pathways. These pathways encompass not only cranial nerve sensory and motor nuclei for processing feeding-related afferent signals and supplying the oromotor musculature but also reticular neurons for orchestrating ingestion and coordinating it with other behaviors that utilize the same musculature. Based on decerebrate studies, this circuit should be sensitive to satiety mechanisms mediated centrally by A2 noradrenergic neurons in the caudal nucleus of the solitary tract (cNST) that are potently activated during satiety. Because the first observable phase of satiety is inhibition of oromotor movements, we hypothesized that norepinephrine (NE) would act to inhibit prehypoglossal neurons in the medullary reticular formation. Using patch-clamp electrophysiology of retrogradely labeled prehypoglossal neurons and calcium imaging to test this hypothesis, we demonstrate that norepinephrine can influence both pre- and postsynaptic properties of reticular neurons through both α1- and α2-adrenoreceptors. The α1-adrenoreceptor agonist phenylephrine (PE) activated an inward current in the presence of TTX and increased the frequency of both inhibitory and excitatory miniature postsynaptic currents. The α2-adrenoreceptor agonist dexmedetomidine (DMT) inhibited cNST-evoked excitatory currents as well as spontaneous and miniature excitatory currents through presynaptic mechanisms. The diversity of adrenoreceptor modulation of these prehypoglossal neurons may reflect their role in a multifunctional circuit coordinating both ingestive and respiratory lingual function.

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Enhancement of Excitatory Synaptic Transmission in Spiny Neurons After Transient Forebrain Ischemia

Journal of Neurophysiology ◽

10.1152/jn.01166.2005 ◽

2006 ◽

Vol 95 (3) ◽

pp. 1537-1544 ◽

Cited By ~ 27

Author(s):

Yuchun Zhang ◽

Ping Deng ◽

Yan Li ◽

Zao C. Xu

Keyword(s):

Pyridoxal Phosphate ◽

Glutamate Release ◽

P2x Receptor ◽

Disulfonic Acid ◽

Forebrain Ischemia ◽

Excitatory Postsynaptic Currents ◽

Transient Forebrain Ischemia ◽

Postsynaptic Currents ◽

Spiny Neurons ◽

Presynaptic Mechanisms

Spiny neurons in the neostriatum are highly vulnerable to ischemia. Enhancement of excitatory synaptic transmissions has been implicated in ischemia-induced excitotoxic neuronal death. Here we report that evoked excitatory postsynaptic currents in spiny neurons were potentiated after transient forebrain ischemia. The ischemia-induced potentiation in synaptic efficacy was associated with an enhancement of presynaptic release as demonstrated by an increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs) and a decrease in the paired-pulse ratio. The amplitude of inward currents evoked by exogenous application of glutamate did not show significant changes after ischemia, suggesting that postsynaptic mechanism is not involved. The ischemia-induced increase in mEPSCs frequency was not affected by blockade of voltage-gated calcium channels, but it was eliminated in the absence of extracellular calcium. Bath application of ATP P2X receptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS) significantly reduced mEPSC frequency in ischemic neurons but had no effects on the control ones. Furthermore, the inhibitory effect of PPADS on ischemic neurons was abolished in Ca2+-free external solution. These results indicate that excitatory synaptic transmissions in spiny neurons are potentiated after ischemia via presynaptic mechanisms. Activation of P2X receptors and the consequent Ca2+ influx might contribute to the ischemia-induced facilitation of glutamate release.

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Vanilloid, purinergic, and CCK receptors activate glutamate release on single neurons of the nucleus tractus solitarius centralis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00054.2011 ◽

2011 ◽

Vol 301 (2) ◽

pp. R394-R401 ◽

Cited By ~ 17

Author(s):

Kirsteen N. Browning ◽

ShuXia Wan ◽

Vander Baptista ◽

R. Alberto Travagli

Keyword(s):

Nucleus Tractus Solitarius ◽

Glutamate Release ◽

Single Neurons ◽

Excitatory Postsynaptic Currents ◽

Cck Receptors ◽

Postsynaptic Currents ◽

C Fibers ◽

Whole Cell Patch Clamp ◽

Vagal Afferent ◽

Paracrine Activation

Baroreceptor inputs to nucleus of the tractus solitarius medialis (mNTS) neurons can be differentiated, among other features, by their response to vanilloid or purinergic agonists, active only on C- or A-fibers, respectively. A major aim of this study was to examine whether neurons of NTS centralis (cNTS), a subnucleus dominated by esophageal inputs, exhibit a similar dichotomy. Since it has been suggested that cholecystokinin (CCK), exerts its gastrointestinal (GI)-related effects via paracrine activation of vagal afferent C-fibers, we tested whether CCK-sensitive fibers impinging upon cNTS neurons are responsive to vanilloid but not purinergic agonists. Using whole cell patch-clamp recordings from cNTS, we recorded miniature excitatory postsynaptic currents (mEPSCs) to test the effects of the vanilloid agonist capsaicin, the purinergic agonist α,β-methylene-ATP (α,β-Met-ATP), and/or CCK-octapeptide (CCK-8s). α,β-Met-ATP, capsaicin; and CCK-8s increased EPSC frequency in 37, 71, and 46% of cNTS neurons, respectively. Approximately 30% of cNTS neurons were responsive to both CCK-8s and α,β-Met-ATP, to CCK-8s and capsaicin, or to α,β-Met-ATP and capsaicin, while 32% of neurons were responsive to all three agonists. All neurons responding to either α,β-Met-ATP or CCK-8s were also responsive to capsaicin. Perivagal capsaicin, which is supposed to induce a selective degeneration of C-fibers, decreased the number of cNTS neurons responding to capsaicin or CCK-8s but not those responding to α,β-Met-ATP. In summary, GI inputs to cNTS neurons cannot be distinguished on the basis of their selective responses to α,β-Met-ATP or capsaicin. Our data also indicate that CCK-8s increases glutamate release from purinergic and vanilloid responsive fibers impinging on cNTS neurons.

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Norepinephrine Facilitates Inhibitory Transmission in Substantia Gelatinosa of Adult Rat Spinal Cord (Part 1)

Anesthesiology ◽

10.1097/00000542-200002000-00030 ◽

2000 ◽

Vol 92 (2) ◽

pp. 473-473 ◽

Cited By ~ 106

Author(s):

Hiroshi Baba ◽

Koki Shimoji ◽

Megumu Yoshimura

Keyword(s):

Spinal Cord ◽

Substantia Gelatinosa ◽

Gamma Aminobutyric Acid ◽

Sprague Dawley ◽

Patch Clamp Technique ◽

Membrane Hyperpolarization ◽

Nociceptive Transmission ◽

Inhibitory Postsynaptic Currents ◽

Adult Rat ◽

Postsynaptic Currents

Background The activation of descending norepinephrine-containing fibers from the brain stem inhibits nociceptive transmission at the spinal level. How these descending noradrenergic pathways exert the analgesic effect is not understood fully. Membrane hyperpolarization of substantia gelatinosa (Rexed lamina II) neurons by the activation of alpha2 receptors may account for depression of pain transmission. In addition, it is possible that norepinephrine affects transmitter release in the substantia gelatinosa. Methods Adult male Sprague-Dawley rats (9-10 weeks of age, 250-300 g) were used in this study. Transverse spinal cord slices were cut from the isolated lumbar cord. The blind whole-cell patch-clamp technique was used to record from neurons. The effects of norepinephrine on the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents were evaluated. Results In the majority of substantia gelatinosa neurons tested, norepinephrine (10-100 microM) dose-dependently increased the frequency of gamma-aminobutyric acid (GABA)ergic and glycinergic miniature inhibitory postsynaptic currents; miniature excitatory postsynaptic currents were unaffected. This augmentation was mimicked by an alpha1-receptor agonist, phenylephrine (10-60 microM), and inhibited by alpha1-receptor antagonists prazosin (0.5 microM) and 2-(2,6-dimethoxyphenoxyethyl) amino-methyl-1,4-benzodioxane (0.5 microM). Neither postsynaptic responsiveness to exogenously applied GABA and glycine nor the kinetics of GABAergic and glycinergic inhibitory postsynaptic currents were affected by norepinephrine. Conclusion These results suggest that norepinephrine enhances inhibitory synaptic transmission in the substantia gelatinosa through activation of presynaptic alpha1 receptors, thus providing a mechanism underlying the clinical use of alpha1 agonists with local anesthetics in spinal anesthesia.

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Enflurane Directly Depresses Glutamate AMPA and NMDA Currents in Mouse Spinal Cord Motor Neurons Independent of Actions on GABAAor Glycine Receptors

Anesthesiology ◽

10.1097/00000542-200010000-00032 ◽

2000 ◽

Vol 93 (4) ◽

pp. 1075-1084 ◽

Cited By ~ 58

Author(s):

Gong Cheng ◽

Joan J. Kendig

Keyword(s):

Spinal Cord ◽

Nmda Receptor ◽

Glutamate Receptors ◽

Dorsal Horn ◽

Motor Neurons ◽

Aminobutyric Acid ◽

Gamma Aminobutyric Acid ◽

Excitatory Postsynaptic Currents ◽

Postsynaptic Currents ◽

Anesthetic Concentration

Background The spinal cord is an important anatomic site at which volatile agents act to prevent movement in response to a noxious stimulus. This study was designed to test the hypothesis that enflurane acts directly on motor neurons to inhibit excitatory synaptic transmission at glutamate receptors. Methods Whole-cell recordings were made in visually identified motor neurons in spinal cord slices from 1- to 4-day-old mice. Excitatory postsynaptic currents (EPSCs) or potentials (EPSPs) were evoked by electrical stimulation of the dorsal root entry area or dorsal horn. The EPSCs were isolated pharmacologically into glutamate N-methyl-d-aspartate (NMDA) receptor- and non-NMDA receptor-mediated components by using selective antagonists. Currents also were evoked by brief pulse pressure ejection of glutamate under various conditions of pharmacologic blockade. Enflurane was made up as a saturated stock solution and diluted in the superfusate; concentrations were measured using gas chromatography. Results Excitatory postsynaptic currents and EPSPs recorded from motor neurons by stimulation in the dorsal horn were mediated by glutamate receptors of both non-NMDA and NMDA subtypes. Enflurane at a general anesthetic concentration (one minimum alveolar anesthetic concentration) reversibly depressed EPSCs and EPSPs. Enflurane also depressed glutamate-evoked currents in the presence of tetrodotoxin (300 nm), showing that its actions are postsynaptic. Block of inhibitory gamma-aminobutyric acid A and glycine receptors by bicuculline (20 micrometer) or strychnine (2 micrometer) or both did not significantly reduce the effects of enflurane on glutamate-evoked currents. Enflurane also depressed glutamate-evoked currents if the inhibitory receptors were blocked and if either D,L-2-amino-5-phosphonopentanoic acid (50 micrometer) or 6-cyano-7-nitroquinoxaline-2,3-dione disodium (10 micrometer) was applied to block NMDA or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-kainate receptors respectively. Conclusions Enflurane exerts direct depressant effects on both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and NMDA glutamate currents in motor neurons. Enhancement of gamma-aminobutyric acid A and glycine inhibition is not needed for this effect. Direct depression of glutamatergic excitatory transmission by a postsynaptic action on motor neurons thus may contribute to general anesthesia as defined by immobility in response to a noxious stimulus.

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Organization and Properties of GABAergic Neurons in Solitary Tract Nucleus (NTS)

Journal of Neurophysiology ◽

10.1152/jn.00038.2008 ◽

2008 ◽

Vol 99 (4) ◽

pp. 1712-1722 ◽

Cited By ~ 64

Author(s):

Timothy W. Bailey ◽

Suzanne M. Appleyard ◽

Young-Ho Jin ◽

Michael C. Andresen

Keyword(s):

Fluorescent Protein ◽

Signal Propagation ◽

Gabaergic Neurons ◽

Visceral Afferents ◽

Egfp Expression ◽

Acid Decarboxylase ◽

Solitary Tract Nucleus ◽

Solitary Tract ◽

Afferent Pathways ◽

Postsynaptic Currents

Cranial visceral afferents enter the brain at the solitary tract nucleus (NTS). GABAergic neurons are scattered throughout the NTS, but their relation to solitary tract (ST) afferent pathways is imprecisely known. We hypothesized that most GABAergic NTS neurons would be connected only indirectly to the ST. We identified GABAergic neurons in brain stem horizontal slices using transgenic mice in which enhanced green fluorescent protein (EGFP) expression was linked to glutamic acid decarboxylase expression (GAD+). Finely graded electrical shocks to ST recruit ST-synchronized synaptic events with all-or-none thresholds and individual waveforms did not change with greater suprathreshold intensities—evidence consistent with initiation by single afferent axons. Most (∼70%) GAD+ neurons received ST-evoked excitatory postsynaptic currents (EPSCs) that had minimally variant latencies (jitter, SD of latency <200 μs) and waveforms consistent with single, direct ST connections (i.e., monosynaptic). Increasing stimulus intensity evoked additional ST-synchronized synaptic responses with jitters >200 μs including inhibitory postsynaptic currents (IPSCs), indicating indirect connections (polysynaptic). Shocks of suprathreshold intensity delivered adjacent (50–300 μm) to the ST failed to excite non-ST inputs to second-order neurons, suggesting a paucity of axons passing near to ST that connected to these neurons. Despite expectations, we found similar ST synaptic patterns in GAD+ and unlabeled neurons. Generally, ST information that arrived indirectly had small amplitudes (EPSCs and IPSCs) and frequency-dependent failures that reached >50% for IPSCs to bursts of stimuli. This ST afferent pathway organization is strongly use-dependent—a property that may tune signal propagation within and beyond NTS.

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