scholarly journals Plasticity of spontaneous excitatory and inhibitory synaptic activity in morphologically defined vestibular nuclei neurons during early vestibular compensation

2012 ◽  
Vol 107 (1) ◽  
pp. 29-41 ◽  
Author(s):  
Mei Shao ◽  
June C. Hirsch ◽  
Kenna D. Peusner
Keyword(s):  
Charge Transfer ◽  
Brain Slices ◽  
Vestibular Nuclei ◽  
Synaptic Activity ◽  
Vestibular Compensation ◽  
Early Recovery ◽  
Inhibitory Postsynaptic Currents ◽  
Principal Cells ◽  
Postsynaptic Currents ◽  
Lesion Side

After unilateral peripheral vestibular lesions, the brain plasticity underlying early recovery from the static symptoms is not fully understood. Principal cells of the chick tangential nucleus offer a subset of morphologically defined vestibular nuclei neurons to study functional changes after vestibular lesions. Chickens show posture and balance deficits immediately after unilateral vestibular ganglionectomy (UVG), but by 3 days most subjects begin to recover, although some remain uncompensated. With the use of whole cell voltage-clamp, spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) and miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) were recorded from principal cells in brain slices 1 and 3 days after UVG. One day after UVG, sEPSC frequency increased on the lesion side and remained elevated at 3 days in uncompensated chickens only. Also by 3 days, sIPSC frequency increased on the lesion side in all operated chickens due to major increases in GABAergic events. Significant change also occurred in decay time of the events. To determine whether fluctuations in frequency and kinetics influenced overall excitatory or inhibitory synaptic drive, synaptic charge transfer was calculated. Principal cells showed significant increase in excitatory synaptic charge transfer only on the lesion side of uncompensated chickens. Thus compensation continues when synaptic charge transfer is in balance bilaterally. Furthermore, excessive excitatory drive in principal cells on the lesion side may prevent vestibular compensation. Altogether, this work is important for it defines the time course and excitatory and inhibitory nature of changing spontaneous synaptic inputs to a morphologically defined subset of vestibular nuclei neurons during critical early stages of recovery after UVG.

scholarly journals Spontaneous Synaptic Activity Is Primarily GABAergic in Vestibular Nucleus Neurons of the Chick Embryo

2003 ◽  
Vol 90 (2) ◽  
pp. 1182-1192 ◽  
Author(s):  
Mei Shao ◽  
June C. Hirsch ◽  
Christian Giaume ◽  
Kenna D. Peusner
Keyword(s):  
Glutamate Receptor ◽  
Vestibular Nucleus ◽  
Glycine Receptor ◽  
Brain Slices ◽  
Reversal Potential ◽  
Cell Voltage ◽  
Synaptic Activity ◽  
Pipette Solution ◽  
Principal Cells ◽  
Postsynaptic Currents

The principal cells of the chick tangential nucleus are vestibular nucleus neurons participating in the vestibular reflexes. In 16-day embryos, the application of glutamate receptor antagonists abolished the postsynaptic responses generated on vestibular-nerve stimulation, but spontaneous synaptic activity was largely unaffected. Here, spontaneous synaptic activity was characterized in principal cells from brain slices at E16 using whole cell voltage-clamp recordings. With KCl electrodes, the frequency of spontaneous inward currents was 3.1 Hz at –60 mV, and the reversal potential was +4 mV. Cs-gluconate pipette solution allowed the discrimination of glycine/GABAA versus glutamate receptor-mediated events according to their different reversal potentials. The ratio for spontaneous excitatory to inhibitory events was about 1:4. Seventy-four percent of the outward events were GABAA, whereas 26% were glycine receptor-mediated events. Both pre- and postsynaptic GABAB receptor effects were shown, with presynaptic GABAB receptors inhibiting 40% of spontaneous excitatory postsynaptic currents (sEPSCs) and 53% of spontaneous inhibitory postsynaptic currents (sIPSCs). With TTX, the frequency decreased ∼50% for EPSCs and 23% for IPSCs. These data indicate that the spontaneous synaptic activity recorded in the principal cells at E16 is primarily inhibitory, action potential-independent, and based on the activation of GABAA receptors that can be modulated by presynaptic GABAB receptors.

scholarly journals Characterization of a Novel Tonic γ-Aminobutyric AcidA Receptor-Mediated Inhibition in Magnocellular Neurosecretory Neurons and Its Modulation by Glia

Endocrinology ◽  
2006 ◽  
Vol 147 (8) ◽  
pp. 3746-3760 ◽  
Author(s):  
Jin Bong Park ◽  
Silvia Skalska ◽  
Javier E. Stern
Keyword(s):  
Gabaa Receptor ◽  
Gabaa Receptors ◽  
Neuronal Excitability ◽  
Tonic Inhibition ◽  
Synaptic Activity ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Gaba Transporters ◽  
Neurosecretory Neurons ◽  
Vasopressin Neurons

In addition to mediating conventional quantal synaptic transmission (also known as phasic inhibition), γ-aminobutyric acidA (GABAA) receptors have been recently shown to underlie a slower, persistent form of inhibition (tonic inhibition). Using patch-clamp electrophysiology and immunohistochemistry, we addressed here whether a GABAA receptor-mediated tonic inhibition is present in supraoptic nucleus (SON) neurosecretory neurons; identified key modulatory mechanisms, including the role of glia; and determined its functional role in controlling SON neuronal excitability. Besides blocking GABAA-mediated inhibitory postsynaptic currents, the GABAA receptor blockers bicuculline and picrotoxin caused an outward shift in the holding current (Itonic), both in oxytocin and vasopressin neurons. Conversely, the high-affinity antagonist gabazine selectively blocked inhibitory postsynaptic currents. Under basal conditions, Itonic was independent on the degree of synaptic activity but was strongly modulated by the activity GABA transporters (GATs), mostly the GAT3 isoform, found here to be localized in SON glial cells/processes. Extracellular activation of GABAergic afferents evoked a small gabazine-insensitive, bicuculline-sensitive current, which was enhanced by GAT blockade. These results suggest that Itonic may be activated by spillover of GABA during conditions of strong and/or synchronous synaptic activity. Blockade of Itonic increased input resistance, induced membrane depolarization and firing activity, and enhanced the input-output function of SON neurons. In summary, our results indicate that GABAA receptors, possibly of different molecular configuration and subcellular distribution, mediate synaptic and tonic inhibition in SON neurons. The latter inhibitory modality plays a major role in modulating SON neuronal excitability, and its efficacy is modulated by the activity of glial GATs.

Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic currents in cultured rat hippocampal neurons

1993 ◽  
Vol 70 (4) ◽  
pp. 1339-1349 ◽  
Author(s):  
M. V. Jones ◽  
N. L. Harrison
Keyword(s):  
Charge Transfer ◽  
Gabaa Receptor ◽  
Hippocampal Neurons ◽  
Slow Component ◽  
Volatile Anesthetics ◽  
Fast Component ◽  
Synaptic Inhibition ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Kinetics Of

1. The effects of the volatile anesthetics enflurane, halothane, and isoflurane on gamma-aminobutyric acid (GABA) receptor-mediated inhibitory postsynaptic currents (IPSCs) were studied in cultured rat hippocampal neurons. The experimental concentrations of anesthetics were measured directly using gas chromatography. All three anesthetics increased the overall duration of IPSCs, measured as the time to half-decay (T1/2). Clinically effective concentrations of anesthetics [between 0.5 and 1.5 times MAC (minimum alveolar concentration)] produced between 100 and 400% increases in T1/2. These effects were fully reversible, and did not involve alterations in the reversal potential for the IPSC (EIPSC). 2. The decay of the IPSC was fitted as a sum of two exponential functions, yielding a fast component (tau fast = 20 ms), and a slow component (tau slow = 77 ms), such that the fast component accounted for 79% of the IPSC amplitude and 52% of the total charge transfer. All three anesthetics produced concentration-related increases in the amplitude and charge transfer of the slow component, while simultaneously decreasing the amplitude and charge transfer of the fast component. Thus T1/2 approximated tau fast under control conditions, but approximated tau slow in the presence of the anesthetics. 3. Varying the calcium chelating agents in the recording pipettes had no effect on the quality or magnitude of alterations in IPSC kinetics produced by halothane, suggesting that variations in intracellular calcium levels are not required for the effect of halothane on the time course of the IPSC. 4. The (+)-stereoisomer of isoflurane produced greater increases in the duration of the IPSC than the (-)-isomer when applied at approximately equal concentrations, suggesting that there is a structurally selective site of interaction for isoflurane that modulates the GABAA receptor. 5. These results suggest that the previously shown abilities of volatile anesthetics to potentiate responses to exogenously applied GABA and to prolong the duration of GABA-mediated synaptic inhibition may be due to an alteration in the gating kinetics of the GABAA receptor/channel complex. Prolongation of synaptic inhibition in the CNS is consistent with the physiological effects that accompany anesthesia and may contribute to the mechanism of anesthetic action.

scholarly journals Structural and functional characterization of dendritic arbors and GABAergic synaptic inputs on interneurons and principal cells in the rat basolateral amygdala

2015 ◽  
Vol 114 (2) ◽  
pp. 942-957 ◽  
Author(s):  
Paul M. Klenowski ◽  
Matthew J. Fogarty ◽  
Arnauld Belmer ◽  
Peter G. Noakes ◽  
Mark C. Bellingham ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Morphological Characteristics ◽  
Cell Types ◽  
Network Activity ◽  
Emotional States ◽  
Inhibitory Postsynaptic Currents ◽  
Principal Cells ◽  
Postsynaptic Currents ◽  
Gabaergic Synapses ◽  
Local Circuitry

The basolateral amygdala (BLA) is a complex brain region associated with processing emotional states, such as fear, anxiety, and stress. Some aspects of these emotional states are driven by the network activity of synaptic connections, derived from both local circuitry and projections to the BLA from other regions. Although the synaptic physiology and general morphological characteristics are known for many individual cell types within the BLA, the combination of morphological, electrophysiological, and distribution of neurochemical GABAergic synapses in a three-dimensional neuronal arbor has not been reported for single neurons from this region. The aim of this study was to assess differences in morphological characteristics of BLA principal cells and interneurons, quantify the distribution of GABAergic neurochemical synapses within the entire neuronal arbor of each cell type, and determine whether GABAergic synaptic density correlates with electrophysiological recordings of inhibitory postsynaptic currents. We show that BLA principal neurons form complex dendritic arborizations, with proximal dendrites having fewer spines but higher densities of neurochemical GABAergic synapses compared with distal dendrites. Furthermore, we found that BLA interneurons exhibited reduced dendritic arbor lengths and spine densities but had significantly higher densities of putative GABAergic synapses compared with principal cells, which was correlated with an increased frequency of spontaneous inhibitory postsynaptic currents. The quantification of GABAergic connectivity, in combination with morphological and electrophysiological measurements of the BLA cell types, is the first step toward a greater understanding of how fear and stress lead to changes in morphology, local connectivity, and/or synaptic reorganization of the BLA.

Development of GABAA Receptor-Mediated Inhibitory Postsynaptic Currents in Hippocampus

2002 ◽  
Vol 88 (6) ◽  
pp. 3097-3107 ◽  
Author(s):  
Matthew I. Banks ◽  
Jason B. Hardie ◽  
Robert A. Pearce
Keyword(s):  
Developmental Regulation ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Cell Voltage ◽  
Fold Increase ◽  
Developmental Changes ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Age Range ◽  
Kinetics Of

Hippocampal CA1 pyramidal cells receive two kinetic classes of GABAA receptor-mediated inhibition: slow dendritic inhibitory postsynaptic currents (GABAA,slow IPSCs) and fast perisomatic (GABAA,fast) IPSCs. These two classes of IPSCs are likely generated by two distinct groups of interneurons, and we have previously shown that the kinetics of the IPSCs have important functional consequences for generating synchronous firing patterns. Here, we studied developmental changes in the properties of GABAA,fast and GABAA,slowspontaneous, miniature, and evoked IPSCs (sIPSCs, mIPSCs, and eIPSCs, respectively) using whole cell voltage-clamp recordings in brain slices from animals aged P10–P35. We found that the rate of GABAA,slow sIPSCs increased by over 70-fold between P11 and P35 (from 0.0017 to 0.12 s−1). Over this same age range, we observed a >3.5-fold increase in the maximal amplitude of GABAA,slow eIPSCs evoked by stratum lacunosum-moleculare (SL-M) stimuli. However, the rate and amplitude of GABAA,slow mIPSCs remained unchanged between P10 and P30, suggesting that the properties of GABAA,slow synapses remained stable over this age range, and that the increase in sIPSC rate and in eIPSC amplitude was due to increased excitability or excitation of GABAA,slow interneurons. This hypothesis was tested using bath application of norepinephrine (NE), which we found at low concentrations (1 μM) selectively increased the rate of GABAA,slow sIPSCs while leaving GABAA,fast sIPSCs unchanged. This effect was observed in animals as young as P13 and was blocked by coapplication of tetrodotoxin, suggesting that NE was acting to increase the spontaneous firing rate of GABAA,slow interneurons and consistent with our hypothesis that developmental changes in GABAA,slow IPSCs are due to changes in presynaptic excitability. In contrast to the changes we observed in GABAA,slow IPSCs, the properties of GABAA,fast sIPSCs remained largely constant between P11 and P35, whereas the rate, amplitude, and kinetics of GABAA,fast mIPSCs showed significant changes between P10 and P30, suggesting counterbalancing changes in action potential-dependent GABAA,fast sIPSCs. These observations suggest differential developmental regulation of the firing properties of GABAA,fast and GABAA,slow interneurons in CA1 between P10 and P35.

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.

GABAA Receptor β3 Subunit Deletion Decreases α2/3 Subunits and IPSC Duration

2003 ◽  
Vol 89 (1) ◽  
pp. 128-134 ◽  
Author(s):  
Epolia Ramadan ◽  
Zhanyan Fu ◽  
Gabriele Losi ◽  
Gregg E. Homanics ◽  
Joseph H. Neale ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Cortical Neurons ◽  
Behavioral Deficits ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Surface Staining ◽  
Α1 Subunit

Deletion of the β3 subunit of the GABAA receptor produces severe behavioral deficits and epilepsy. GABAA receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) in cortical neurons in cultures from β3 −/− mice were significantly faster than those in β3 +/+ mice and were more prolonged by zolpidem. Surface staining revealed that the number of β2/3, α2, and α3 (but not of α1) subunit-expressing neurons and the intensity of subunit clusters were significantly reduced in β3 −/− mice. Transfection of β3 −/− neurons with β3 cDNA restored β2/3, α2, and α3 subunits immunostaining and slowed mIPSCs decay. We show that the deletion of the β3 subunit causes the loss of a subset of GABAA receptors with α2 and α3 subunits while leaving a receptor population containing predominantly α1 subunit with fast spontaneous IPSC decay and increased zolpidem sensitivity.

Altered desensitization produces enhancement of EPSPs in neocortical neurons

1994 ◽  
Vol 72 (2) ◽  
pp. 1032-1036 ◽  
Author(s):  
M. R. Pelletier ◽  
J. J. Hablitz
Keyword(s):  
Nmda Receptors ◽  
Time Course ◽  
Glutamate Release ◽  
Epileptiform Activity ◽  
Brain Slices ◽  
Synaptic Activity ◽  
Membrane Properties ◽  
Repetitive Firing ◽  
Resting Membrane Potential ◽  
Bath Application

1. Neocortical brain slices were prepared from rats (35–50 days of age) and maintained in vitro. Intracellular recordings were obtained from neurons in cortical layers II/III. The effect of bath application of cyclothiazide (CYZ), a potent blocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor desensitization, on evoked synaptic activity and passive membrane properties was investigated. 2. Bath application of CYZ did not significantly affect resting membrane potential, input resistance, or repetitive firing. CYZ increased both the amplitude and duration of evoked excitatory postsynaptic potentials (EPSPs). Polysynaptic responses were also augumented. These effects persisted after the blockade of N-methyl-D-aspartate (NMDA) receptors with D-2-amino-5-phosphonovaleric acid (D-APV). The magnitude of these effects appeared to vary directly with stimulation intensity and presumably, amount of glutamate release. 3. Epileptiform activity was induced by bath application of bicuculline methiodide. The amplitude and duration of evoked paroxysmal discharges were increased by CYZ. Similar results were seen in presence of D-APV. 4. These results indicate that CYZ has significant effects on synaptic transmission. Desensitization of non-NMDA receptors may be an important mechanism for determining the time course of EPSPs and in curtailing epileptiform responses in the rat neocortex.

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.

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