Differential Short-Term Changes in GABAergic or Glycinergic Synaptic Efficacy on Rat Hypoglossal Motoneurons

2001 ◽  
Vol 86 (2) ◽  
pp. 565-574 ◽  
Author(s):  
Roberta Donato ◽  
Andrea Nistri
Keyword(s):  
Neonatal Rat ◽  
Patch Clamp Recording ◽  
Short Term ◽  
Hypoglossal Motoneurons ◽  
Whole Cell Patch Clamp ◽  
Gabaergic Synapses ◽  
Synaptic Changes ◽  
Rat Brain Slice ◽  
Neonatal Rat Brain ◽  
Brain Slice Preparation

Using whole cell patch-clamp recording from hypoglossal motoneurons of a neonatal rat brain slice preparation, we investigated short-term changes in synaptic transmission mediated by GABA or glycine. In 1.5 mM extracellular Ca2+[Ca2+]o, pharmacologically isolated GABAergic or glycinergic currents were elicited by electrical stimulation of the reticular formation. At low stimulation frequency, glycinergic currents were larger and faster than GABAergic ones. GABAergic currents were strongly facilitated by pulse trains at 5 or 10 Hz without apparent depression. This phenomenon persisted after pharmacological block of GABABreceptors. Glycinergic currents were comparatively much less enhanced than GABAergic currents. One possible mechanism to account for this difference is that GABAergic currents decayed so slowly that consecutive responses summated over an incrementing baseline. However, while synaptic summation appeared at ≥10-Hz stimulation, at 5 Hz strong facilitation developed with minimal summation of GABA-mediated currents. Glycinergic currents decayed so fast that summation was minimal. As [Ca2+]o is known to shape short-term synaptic changes, we examined if varying [Ca2+]o could differentially affect facilitation of GABA- or glycine-operated synapses. With 5 mM [Ca2+]o, the frequency of spontaneous GABAergic or glycinergic currents appeared much higher but GABAergic current facilitation was blocked (and replaced by depression), whereas glycinergic currents remained slightly facilitated. [Ca2+]omanipulation thus brought about distinct processes responsible for facilitation of GABAergic or glycinergic transmission. Our data therefore demonstrate an unexpectedly robust, short-term increase in the efficiency of GABAergic synapses that can become at least as effective as glycinergic synapses.

Developmental Changes in the Fidelity and Short-Term Plasticity of GABAergic Synapses in the Neonatal Rat Dorsal Horn

2008 ◽  
Vol 99 (6) ◽  
pp. 3144-3150 ◽  
Author(s):  
Rachel A. Ingram ◽  
Maria Fitzgerald ◽  
Mark L. Baccei
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Receptive Fields ◽  
Neuronal Firing ◽  
Neonatal Rat ◽  
Superficial Dorsal Horn ◽  
Short Term ◽  
Dorsal Horn Neurons ◽  
Gabaergic Synapses

The lower thresholds and increased excitability of dorsal horn neurons in the neonatal rat suggest that inhibitory processing is less efficient in the immature spinal cord. This is unlikely to be explained by an absence of functional GABAergic inhibition because antagonism of γ-aminobutyric acid (GABA) type A receptors augments neuronal firing in vivo from the first days of life. However, it is possible that more subtle deficits in GABAergic signaling exist in the neonate, such as decreased reliability of transmission or greater depression during repetitive stimulation, both of which could influence the relative excitability of the immature spinal cord. To address this issue we examined monosynaptic GABAergic inputs onto superficial dorsal horn neurons using whole cell patch-clamp recordings made in spinal cord slices at a range of postnatal ages (P3, P10, and P21). The amplitudes of evoked inhibitory postsynaptic currents (IPSCs) were significantly lower and showed greater variability in younger animals, suggesting a lower fidelity of GABAergic signaling at early postnatal ages. Paired-pulse ratios were similar throughout the postnatal period, whereas trains of stimuli (1, 5, 10, and 20 Hz) revealed frequency-dependent short-term depression (STD) of IPSCs at all ages. Although the magnitude of STD did not differ between ages, the recovery from depression was significantly slower at immature GABAergic synapses. These properties may affect the integration of synaptic inputs within developing superficial dorsal horn neurons and thus contribute to their larger receptive fields and enhanced afterdischarge.

scholarly journals Morphine-induced synaptic plasticity in the VTA is reversed by HDAC inhibition

2016 ◽  
Vol 116 (3) ◽  
pp. 1093-1103 ◽  
Author(s):  
Michael E. Authement ◽  
Ludovic D. Langlois ◽  
Haifa Kassis ◽  
Shawn Gouty ◽  
Matthieu Dacher ◽  
...  
Keyword(s):  
Behavioral Plasticity ◽  
Drugs Of Abuse ◽  
Patch Clamp Recording ◽  
Whole Cell Patch Clamp ◽  
Synaptic Changes ◽  
Induced Changes ◽  
And Behavior ◽  
H3 Acetylation

Dopamine (DA) dysfunction originating from the ventral tegmental area (VTA) occurs as a result of synaptic abnormalities following consumption of drugs of abuse and underlies behavioral plasticity associated with drug abuse. Drugs of abuse can cause changes in gene expression through epigenetic mechanisms in the brain that underlie some of the lasting neuroplasticity and behavior associated with addiction. Here we investigated the function of histone acetylation and histone deacetylase (HDAC)2 in the VTA in recovery of morphine-induced synaptic modifications following a single in vivo exposure to morphine. Using a combination of immunohistochemistry, Western blot, and whole cell patch-clamp recording in rat midbrain slices, we show that morphine increased HDAC2 activity in VTA DA neurons and reduced histone H3 acetylation at lysine 9 (Ac-H3K9) in the VTA 24 h after the injection. Morphine-induced synaptic changes at glutamatergic synapses involved endocannabinoid signaling to reduce GABAergic synaptic strength onto VTA DA neurons. Both plasticities were recovered by in vitro incubation of midbrain slices with a class I-specific HDAC inhibitor (HDACi), CI-994, through an increase in acetylation of histone H3K9. Interestingly, HDACi incubation also increased levels of Ac-H3K9 and triggered GABAergic and glutamatergic plasticities in DA neurons of saline-treated rats. Our results suggest that acute morphine-induced changes in VTA DA activity and synaptic transmission engage HDAC2 activity locally in the VTA to maintain synaptic modifications through histone hypoacetylation.

scholarly journals Inhibition of microglial activation by minocycline reduced preoligodendrocyte injury in a neonatal rat brain slice model

2018 ◽  
Vol 156 (6) ◽  
pp. 2271-2280 ◽  
Author(s):  
Junrong Huang ◽  
Gang Liu ◽  
Bowen Shi ◽  
Guochen Shi ◽  
Xiaomin He ◽  
...  
Keyword(s):  
Rat Brain ◽  
Microglial Activation ◽  
Brain Slice ◽  
Neonatal Rat ◽  
Rat Brain Slice ◽  
Neonatal Rat Brain

Early anoxia-induced vesicular glutamate release results from mobilization of calcium from intracellular stores

1993 ◽  
Vol 70 (1) ◽  
pp. 1-7 ◽  
Author(s):  
A. N. Katchman ◽  
N. Hershkowitz
Keyword(s):  
Calcium Influx ◽  
Glutamate Release ◽  
Hippocampal Slices ◽  
Calcium Currents ◽  
Patch Clamp Recording ◽  
Ca1 Neurons ◽  
Whole Cell Patch Clamp ◽  
Mepsc Frequency ◽  
Synaptic Changes

1. The cause of the increased frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) resulting from anoxia was investigated in CA1 neurons of the in vitro rat hippocampal slice. These neurons were examined by whole-cell patch-clamp recording, and hypoxia was induced by switching the perfusion of the slice from oxygenated artificial cerebral spinal fluid (ACSF) to ACSF saturated with 95% N2-5% O2. Except where noted, experiments were carried out in ACSF containing 1 microM tetrodotoxin (TTX). 2. Although anoxia resulted in a significant increase in the frequency of mEPSCs, the amplitude, rise time, and half-decay time of the mEPSCs were unchanged. This increase in frequency indicates that there is a change in presynaptic neurotransmitter release mechanisms, probably an increase in calcium concentration, soon after the onset of anoxia. The unchanged kinetics and amplitude of the mEPSCs indicate that anoxic-induced synaptic changes are not a result of changes in the postsynaptic glutamate receptor. 3. When hippocampal slices were exposed to anoxic conditions in ACSF with calcium excluded, an increase in mEPSC frequency equal to that in normal ACSF was observed. When 0.2 mM of CdCl2 was added to the zero-calcium ACSF, anoxia still resulted in increases in mEPSC frequency equal to those of normal ACSF. It is therefore concluded that the anoxia-induced increase in mEPSC frequency does not result from an increase in a transmembrane calcium influx. The zero-calcium plus 0.2 mM CdCl2 ACSF solution completely abolished orthodromically elicited synaptic potential (in the absence of TTX), indicating that calcium currents that mediate normal orthodromic transmitter release were completely abolished in the latter experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals 1 H/ 13 C NMR metabolomics in a neonatal rat brain slice model of early and late mild hypothermia treatments of asphyxia

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Jia Liu ◽  
Lawrence Litt ◽  
Jeffrey G. Pelton ◽  
Mark Segal ◽  
Mark J.S. Kelly ◽  
...  
Keyword(s):  
Rat Brain ◽  
Brain Slice ◽  
Mild Hypothermia ◽  
Neonatal Rat ◽  
Nmr Metabolomics ◽  
Rat Brain Slice ◽  
Neonatal Rat Brain ◽  
C Nmr

scholarly journals Intrinsic excitability differs between murine hypoglossal and spinal motoneurons

2016 ◽  
Vol 115 (5) ◽  
pp. 2672-2680 ◽  
Author(s):  
M. A. Tadros ◽  
A. J. Fuglevand ◽  
A. M. Brichta ◽  
R. J. Callister
Keyword(s):  
Action Potentials ◽  
Membrane Properties ◽  
Intrinsic Excitability ◽  
Spinal Motoneurons ◽  
Patch Clamp Recording ◽  
Electrophysiological Properties ◽  
Hypoglossal Motoneurons ◽  
Whole Cell Patch Clamp ◽  
Two Populations ◽  
Passive Membrane Properties

Motoneurons differ in the behaviors they control and their vulnerability to disease and aging. For example, brain stem motoneurons such as hypoglossal motoneurons (HMs) are involved in licking, suckling, swallowing, respiration, and vocalization. In contrast, spinal motoneurons (SMs) innervating the limbs are involved in postural and locomotor tasks requiring higher loads and lower movement velocities. Surprisingly, the properties of these two motoneuron pools have not been directly compared, even though studies on HMs predominate in the literature compared with SMs, especially for adult animals. Here we used whole cell patch-clamp recording to compare the electrophysiological properties of HMs and SMs in age-matched neonatal mice (P7–P10). Passive membrane properties were remarkably similar in HMs and SMs, and afterhyperpolarization properties did not differ markedly between the two populations. HMs had narrower action potentials (APs) and a faster upstroke on their APs compared with SMs. Furthermore, HMs discharged APs at higher frequencies in response to both step and ramp current injection than SMs. Therefore, while HMs and SMs have similar passive properties, they differ in their response to similar levels of depolarizing current. This suggests that each population possesses differing suites of ion channels that allow them to discharge at rates matched to the different mechanical properties of the muscle fibers that drive their distinct motor functions.

scholarly journals Local circuit input to the medullary reticular formation from the rostral nucleus of the solitary tract

2008 ◽  
Vol 295 (5) ◽  
pp. R1391-R1408 ◽  
Author(s):  
J. Nasse ◽  
D. Terman ◽  
S. Venugopal ◽  
G. Hermann ◽  
R. Rogers ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Reticular Formation ◽  
Calcium Imaging ◽  
Neonatal Rat ◽  
Solitary Tract ◽  
Patch Clamp Recording ◽  
Whole Cell ◽  
Cell Patch Clamp ◽  
Whole Cell Patch Clamp ◽  
Stimulation Of

The intermediate reticular formation (IRt) subjacent to the rostral (gustatory) nucleus of the solitary tract (rNST) receives projections from the rNST and appears essential to the expression of taste-elicited ingestion and rejection responses. We used whole cell patch-clamp recording and calcium imaging to characterize responses from an identified population of prehypoglossal neurons in the IRt to electrical stimulation of the rNST in a neonatal rat pup slice preparation. The calcium imaging studies indicated that IRt neurons could be activated by rNST stimulation and that many neurons were under tonic inhibition. Whole cell patch-clamp recording revealed mono- and polysynaptic projections from the rNST to identified prehypoglossal neurons. The projection was primarily excitatory and glutamatergic; however, there were some inhibitory GABAergic projections, and many neurons received excitatory and inhibitory inputs. There was also evidence of disinhibition. Overall, bath application of GABAA antagonists increased the amplitude of excitatory currents, and, in several neurons, stimulation of the rNST systematically decreased inhibitory currents. We have hypothesized that the transition from licks to gapes by natural stimuli, such as quinine monohydrochloride, could occur via such disinhibition. We present an updated dynamic model that summarizes the complex synaptic interface between the rNST and the IRt and demonstrates how inhibition could contribute to the transition from ingestion to rejection.

Voltage-Activated K+ Currents of Hypoglossal Motoneurons in a Brain Stem Slice Preparation From the Neonatal Rat

1999 ◽  
Vol 81 (1) ◽  
pp. 140-148 ◽  
Author(s):  
Remigijus Lape ◽  
Andrea Nistri
Keyword(s):  
Brain Stem ◽  
Time Constant ◽  
Onset Time ◽  
Outward Current ◽  
Membrane Depolarization ◽  
Neonatal Rat ◽  
Slice Preparation ◽  
Hypoglossal Motoneurons ◽  
Whole Cell Patch Clamp ◽  
Outward Currents

Lape, Remigijus and Andrea Nistri. Voltage-activated K+ currents of hypoglossal motoneurons in a brain stem slice preparation from the neonatal rat. J. Neurophysiol. 81: 140–148, 1999. Whole cell, patch-clamp recordings were performed on motoneurons of the hypoglossus nucleus in a brain stem slice preparation from the neonatal rat brain. The aim was to investigate transient outward currents activated by membrane depolarization under voltage clamp conditions. In a Ca2+-free medium containing tetrodotoxin and Cs+, depolarizing voltage commands from a holding potential of −50 mV induced slow outward currents ( I slow) with 34 ± 6 ms (SE) onset time constant at 0 mV and minimal decline during a 1 s pulse depolarization. When the depolarizing command was preceded by a prepulse to −110 mV, the outward current became biphasic as it comprised a faster component ( I fast), which could be investigated in isolation by subtracting the two sets of records. I fast showed rapid kinetics (9 ± 4 ms 10–90% rise time and 70 ± 20 ms decay time constant at 0 mV) and strong voltage-dependent inactivation (half inactivation was at −92.9 ± 0.2 mV) from which it readily recovered with a biexponential timecourse (4.4 ± 0.6 and 17 ± 2 ms time constants at −110 mV membrane potential). I slow was selectively blocked by TEA (10–30 mM) while I fast was preferentially depressed by 2–3 mM 4-aminopyridine. Analysis of tail current reversal indicated that both I slow and I fast were predominantly due to K+ with minor permeability to Na+ (92/1 and 50/1, respectively). These results suggest that membrane depolarization activated distinct K+ conductances that, in view of their largely dissimilar kinetics, are likely to play a differential role in regulating the firing behavior of hypoglossal motoneurons.

Unitary excitatory synaptic currents in preganglionic neurons mediated by two distinct groups of interneurons in neonatal rat sacral parasympathetic nucleus

1996 ◽  
Vol 76 (1) ◽  
pp. 215-226 ◽  
Author(s):  
I. Araki ◽  
W. C. De Groat
Keyword(s):  
Nmda Receptor Antagonist ◽  
Neonatal Rat ◽  
Patch Clamp Recording ◽  
Lumbosacral Spinal Cord ◽  
Postsynaptic Currents ◽  
Preganglionic Neurons ◽  
Sacral Parasympathetic Nucleus ◽  
Whole Cell Patch Clamp ◽  
Two Populations ◽  
Stimulation Of

1. Excitatory postsynaptic currents (EPSCs) in parasympathetic preganglionic neurons (PGNs) were examined by the use of the whole cell patch-clamp recording technique in slice preparations of the neonatal rat lumbosacral spinal cord. Synaptic responses were evoked in PGNs by extracellular stimulation of a neighboring interneuron. 2. Stimulation of interneurons medial to the sacral parasympathetic nucleus (SPN) elicited EPSCs or inhibitory postsynaptic currents in 58 and 11%, respectively, of PGNs. Stimulation of interneurons dorsal to the SPN evoked EPSCs in 70% of PGNs. 3. EPSCs occurred at short latency (2.1 ms) and were usually elicited in an all-or-none manner, indicating that they were monosynaptic and mediated by a single interneuron (i.e., unitary). 4. EPSCs were mediated by both non-N-methyl-D-aspartate (non-NMDA) and NMDA receptors. 5. Unitary excitatory postsynaptic potentials evoked by single stimuli did not induce action potentials in PGNs, but repetitive stimulation (> 20 Hz) of the single interneurons could evoke firing of PGNs. 2-Amino-5-phosphonovalerate, an NMDA receptor antagonist, reduced the synaptic depolarization induced in PGNs by high-frequency interneuronal impulses. 6. EPSCs mediated by dorsal interneurons were smaller in amplitude (36.3 +/- 15.7 pA, mean +/- SD) than EPSCs mediated by medial interneurons (88.4 +/- 45.7 pA). 7. Paired-pulse facilitation of EPSCs was observed in PGNs (147.2 +/- 26.2%). The degree of facilitation was higher in dorsal (174.6 +/- 10.3%) than in medial interneuronal pathways (120.9 +/- 3.6%). Within each of interneuronal pathways the degree of facilitation was independent of the magnitude of the unitary EPSC. 8. The results show that PGNs receive monosynaptic glutamatergic excitatory inputs from two distinct populations of interneurons in the dorsal and medial regions of the SPN. These two populations of interneurons are likely to have different functions in the regulation of the preganglionic outflow to the pelvic organs.

scholarly journals Circadian Rhythm in Inhibitory Synaptic Transmission in the Mouse Suprachiasmatic Nucleus

2004 ◽  
Vol 92 (1) ◽  
pp. 311-319 ◽  
Author(s):  
Jason Itri ◽  
Stephan Michel ◽  
James A. Waschek ◽  
Christopher S. Colwell
Keyword(s):  
Circadian Rhythm ◽  
Synaptic Transmission ◽  
Suprachiasmatic Nucleus ◽  
Constant Darkness ◽  
Patch Clamp Recording ◽  
Inhibitory Synaptic Transmission ◽  
Whole Cell Patch Clamp ◽  
Light:Dark Cycle ◽  
Brain Slice Preparation ◽  
Deficient Mice

It is widely accepted that most suprachiasmatic nucleus (SCN) neurons express the neurotransmitter GABA and are likely to use this neurotransmitter to regulate excitability within the SCN. To evaluate the possibility that inhibitory synaptic transmission varies with a circadian rhythm within the mouse SCN, we used whole cell patch-clamp recording in an acute brain slice preparation to record GABA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). We found that the sIPSC frequency in the dorsal SCN (dSCN) exhibited a TTX-sensitive daily rhythm that peaked during the late day and early night in mice held in a light:dark cycle. We next evaluated whether vasoactive intestinal peptide (VIP) was responsible for the observed rhythm in IPSC frequency. Pretreatment of SCN slices with VPAC1/VPAC2- or VPAC2-specific receptor antagonists prevented the increase in sIPSC frequency in the dSCN. The rhythm in sIPSC frequency was absent in VIP/peptide histidine isoleucine (PHI)-deficient mice. Finally, we were able to detect a rhythm in the frequency of inhibitory synaptic transmission in mice held in constant darkness that was also dependent on VIP and the VPAC2 receptor. Overall, these data demonstrate that there is a circadian rhythm in GABAergic transmission in the dorsal region of the mouse SCN and that the VIP is required for expression of this rhythm.

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