Electrophysiological Assessment of Synaptic Transmission in Brain Slices

2002 ◽  
Author(s):  
Jeff Weiner
Keyword(s):  
Synaptic Transmission ◽  
Brain Slices

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.

Major Role For Tonic GABAA Conductances in Anesthetic Suppression of Intrinsic Neuronal Excitability

2004 ◽  
Vol 92 (3) ◽  
pp. 1658-1667 ◽  
Author(s):  
Mark C. Bieda ◽  
M. Bruce MacIver
Keyword(s):  
Synaptic Transmission ◽  
Neuronal Excitability ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Intrinsic Excitability ◽  
High Potassium ◽  
Ca1 Neurons ◽  
Adult Rat ◽  
Adult Rat Brain ◽  
Sites Of Action

Anesthetics appear to produce neurodepression by altering synaptic transmission and/or intrinsic neuronal excitability. Propofol, a widely used anesthetic, has proposed effects on many targets, ranging from sodium channels to GABAA inhibition. We examined effects of propofol on the intrinsic excitability of hippocampal CA1 neurons (primarily interneurons) recorded from adult rat brain slices. Propofol strongly depressed action potential production induced by DC injection, synaptic stimulation, or high-potassium solutions. Propofol-induced depression of intrinsic excitability was completely reversed by bicuculline and picrotoxin but was strychnine-insensitive, implicating GABAA but not glycine receptors. Propofol strongly enhanced inhibitory postsynaptic currents (IPSCs) and induced a tonic GABAA-mediated current. We pharmacologically differentiated tonic and phasic (synaptic) GABAA-mediated inhibition using the GABAA receptor antagonist SR95531 (gabazine). Gabazine (20 μM) completely blocked both evoked and spontaneous IPSCs but failed to block the propofol-induced depression of intrinsic excitability, implicating tonic, but not phasic, GABAA inhibition. Glutamatergic synaptic responses were not altered by propofol (≤30 μM). Similar results were found in both interneurons and pyramidal cells and with the chemically unrelated anesthetic thiopental. These results suggest that suppression of CA1 neuron intrinsic excitability, by these anesthetics, is largely due to activation of tonic GABAA conductances; although other sites of action may play important roles in affecting synaptic transmission, which also can produce strong neurodepression. We propose that for some anesthetics, suppression of intrinsic excitability, mediated by tonic GABAA conductances, operates in conjunction with effects on synaptic transmission, mediated by other mechanisms, to depress hippocampal function during anesthesia.

Activation of Group I mGluRs Is Necessary for Induction of Long-Term Depression at Striatal Synapses

2001 ◽  
Vol 86 (5) ◽  
pp. 2405-2412 ◽  
Author(s):  
Ki-Wug Sung ◽  
Sukwoo Choi ◽  
David M. Lovinger
Keyword(s):  
Synaptic Transmission ◽  
Metabotropic Glutamate Receptors ◽  
Brain Slices ◽  
High Frequency Stimulation ◽  
Long Term Depression ◽  
Selective Antagonist ◽  
Group I ◽  
Group Ii ◽  
Mglur Antagonist

Activation of metabotropic glutamate receptors (mGluRs), which are coupled to G proteins, has important roles in certain forms of synaptic plasticity including corticostriatal long-term depression (LTD). In the present study, extracellular field potential and whole cell voltage-clamp recording techniques were used to investigate the effect of mGluR antagonists with different subtype specificity on high-frequency stimulation (HFS)-induced LTD of synaptic transmission in the striatum of brain slices obtained from 15-to 25-day-old rats. Induction of LTD was prevented during exposure to the nonselective mGluR antagonist (RS)-α-methyl-4-carboxyphenylglycine (500 μM). The group I mGluR-selective antagonists ( S)-4-carboxy-phenylglycine (50 μM) and (RS)-1-aminoindan-1,5-dicarboxylic acid (100 μM) prevented induction of LTD when applied before and during HFS. The mGluR1-selective antagonist 7-(Hydroxyimino) cyclopropa[b]chromen-1a-carboxylate ethyl ester (80 μM) also blocked LTD induction. Unexpectedly, the mGluR5-selective antagonist 2-methyl-6-(phenylethyl)-pyridine (10 μM) also prevented LTD induction. The group II mGluR antagonist LY307452 (10 μM) did not block LTD induction at corticostriatal synapses, but LY307452 was able to block transient synaptic depression induced by the group II agonist LY314593. None of the antagonists had any effect on basal synaptic transmission at the concentrations used, and mGluR antagonists did not reverse LTD when applied beginning 20 min after HFS. These results suggest that both group I mGluR subtypes contribute to the induction of LTD at corticostriatal synapses.

scholarly journals Dopaminergic Modulation of Local Network Activity in Rat Prefrontal Cortex

2007 ◽  
Vol 97 (6) ◽  
pp. 4120-4128 ◽  
Author(s):  
Susanta Bandyopadhyay ◽  
John J. Hablitz
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Receptor Agonist ◽  
Neuronal Networks ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Lateral Spread ◽  
Local Network ◽  
Evoked Activity

Dopamine modulates prefrontal cortex excitability in complex ways. Dopamine's net effect on local neuronal networks is therefore difficult to predict based on studies on pharmacologically isolated excitatory or inhibitory connections. In the present work, we have studied the effects of dopamine on evoked activity in acute rat brain slices when both excitation and inhibition are intact. Whole cell recordings from layer II/III pyramidal cells under conditions of normal synaptic transmission showed that bath-applied dopamine (30 μM) increased the outward inhibitory component of composite postsynaptic currents, whereas inward excitatory currents were not significantly affected. Optical imaging with the voltage-sensitive dye N-(3-(triethylammonium)propyl)-4-(4-(p-diethylaminophenyl)buta-dienyl)pyridinium dibromide revealed that bath application of dopamine significantly decreased the amplitude, duration, and lateral spread of activity in local cortical networks. This effect of dopamine was observed both with single and train (5 at 20 Hz) stimuli. The effect was mimicked by the D1-like receptor agonist R(+)-6-chloro-7,8-dihydroxy-1-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (1 μM) and was blocked by R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (10 μM), a selective antagonist for D1-like receptors. The D2-like receptor agonist quinpirole (10 μM) had no significant effect on evoked dye signals. Our results suggest that dopamine's effect on inhibition dominates over that on excitation under conditions of normal synaptic transmission. Such neuromodulation by dopamine may be important for maintenance of stability in local neuronal networks in the prefrontal cortex.

Hippocampal Interneurons Are Excited Via Serotonin-Gated Ion Channels

1997 ◽  
Vol 78 (5) ◽  
pp. 2493-2502 ◽  
Author(s):  
Lori L. McMahon ◽  
Julie A. Kauer
Keyword(s):  
Ion Channels ◽  
Synaptic Transmission ◽  
Dentate Gyrus ◽  
Granule Cells ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
Negative Slope ◽  
Patch Clamp Recording ◽  
Gated Ion Channels

McMahon, Lori L. and Julie A. Kauer. Hippocampal interneurons are excited via serotonin-gated ion channels. J. Neurophysiol. 78: 2493–2502, 1997. Serotonergic neurons of the median raphe nucleus heavily innervate hippocampal GABAergic interneurons located in stratum radiatum of area CA1, suggesting that this strong subcortical projection may modulate interneuron excitability. Using whole cell patch-clamp recording from interneurons in brain slices, we tested the effects of serotonin (5-HT) on the physiological properties of these interneurons. Serotonin produces a rapid inward current that persists when synaptic transmission is blocked by tetrodotoxin and cobalt, and is unaffected by ionotropic glutamate and γ-aminobutyric acid (GABA) receptor antagonists. The 5-HT–induced current was independent of G-protein activation. Pharmacological evidence indicates that 5-HT directly excites these interneurons through activation of 5-HT3 receptors. At membrane potentials negative to −55 mV, the current-voltage ( I-V) relationship of the 5-HT current displays a region of negative slope conductance. Therefore the response of interneurons to 5-HT strongly depends on membrane potential and increases greatly as cells are depolarized. Removal of extracellular calcium, but not magnesium, increases the amplitude of 5-HT–induced currents and removes the region of negative slope conductance, thereby linearizing the I-V relationship. The axons of 5-HT–responsive interneurons ramify widely within CA1; some of these interneurons also project to and arborize extensively in the dentate gyrus. The organization of these inhibitory connections strongly suggests that these cells regulate excitability of both CA1 pyramidal cells and dentate granule cells. As our results indicate that 5-HT may mediate fast excitatory synaptic transmission onto these interneurons, serotonergic inputs can simultaneously modulate the output of both hippocampus and dentate gyrus.

scholarly journals A dialogue between glia and neurons in the retina: modulation of neuronal excitability

2004 ◽  
Vol 1 (3) ◽  
pp. 245-252 ◽  
Author(s):  
ERIC A. NEWMAN
Keyword(s):  
Synaptic Transmission ◽  
Glial Cells ◽  
Neuronal Excitability ◽  
Ganglion Cells ◽  
Brain Slices ◽  
Müller Cells ◽  
Muller Cells ◽  
Signaling Mechanisms ◽  
Bidirectional Signaling ◽  
Stimulation Of

Bidirectional signaling between neurons and glial cells has been demonstrated in brain slices and is believed to mediate glial modulation of synaptic transmission in the CNS. Our laboratory has characterized similar neuron–glia signaling in the mammalian retina. We find that light-evoked neuronal activity elicits Ca2+ increases in Müller cells, which are specialized retinal glial cells. Neuron to glia signaling is likely mediated by the release of ATP from neurons and is potentiated by adenosine. Glia to neuron signaling has also been observed and is mediated by several mechanisms. Stimulation of glial cells can result in either facilitation or depression of synaptic transmission. Release of D-serine from Müller cells might also potentiate NMDA receptor transmission. Müller cells directly inhibit ganglion cells by releasing ATP, which, following hydrolysis to adenosine, activates neuronal A1 receptors. The existence of bidirectional signaling mechanisms indicates that glial cells participate in information processing in the retina.

Glutamatergic Synaptic Plasticity in the Periaqueductal Gray Governs Fear-induced Depression-like Behavior in Rats

2017 ◽  
Vol 41 (S1) ◽  
pp. S633-S633 ◽  
Author(s):  
Y.C. Ho ◽  
M.C. Hsieh ◽  
C.Y. Lai ◽  
H.Y. Peng
Keyword(s):  
Synaptic Transmission ◽  
Learned Helplessness ◽  
Depressive Disorders ◽  
Glutamate Release ◽  
Brain Slices ◽  
Periaqueductal Gray ◽  
Control Group ◽  
Patch Clamp Recording ◽  
Whole Cell Patch Clamp ◽  
Competing Interest

IntroductionMajor depressive disorder affecting more than 110 million people worldwide every year is a heterogeneous illness influenced by a variety of factors, including repeated stressful factors. Despite widely research during the past several decades, the pathophysiology and neurobiological mechanisms of depressive disorders remain unclear. Ventrolateral periaqueductal gray (vlPAG), a midbrain nucleus, has been considered as an important part of the circuitry that involves in stress-induced depression-like behaviors. Dysregulation of glutamatergic neurotransmission in depressed patients suggests that glutamate-mediated excitatory system is critical involved in the depressive disorders.ObjectivesIt is still unclear that whether vlPAG involves in fear condition-elicited depression-like behavior.AimsWe investigated the synaptic transmission in the vlPAG to examine whether vlPAG participates in fear-induced depression-like behavior in rats.MethodsDepression-like behaviors, in the rats, were induced by learned helplessness procedure. The synaptic transmission was conducted by whole-cell patch-clamp recording in the rat brain slices containing periaqueductal gray.ResultsRats receiving learned helplessness procedure displayed high failure rate in the escapable foot-shock test compared to control group. Both amplitude and frequency of miniature excitatory postsynaptic currents were significant reduced compared to control group, suggesting reduced presynaptic glutamate release and postsynaptic responses were involved in the learned helplessness procedure-induced depression behavior in rats.ConclusionsReduced glutamatergic transmission in the vlPAG contributes to learned helplessness procedure-induced depression-like behavior in rats through pre – and post-synaptic mechanisms.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Oxytocin Regulates Synaptic Transmission in the Sensory Cortices in a Developmentally Dynamic Manner

2021 ◽  
Vol 15 ◽  
Author(s):  
Jing Zhang ◽  
Shu-Jing Li ◽  
Wanying Miao ◽  
Xiaodi Zhang ◽  
Jing-Jing Zheng ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Knockout Mice ◽  
Pyramidal Neurons ◽  
Neural Circuit ◽  
Brain Slices ◽  
Building Blocks ◽  
Sensory Experience ◽  
Conditional Knockout ◽  
Excitatory Synaptic Transmission ◽  
Loss Of Function

The development and stabilization of neuronal circuits are critical to proper brain function. Synapses are the building blocks of neural circuits. Here we examine the effects of the neuropeptide oxytocin on synaptic transmission in L2/3 pyramidal neurons of the barrel field of the primary somatosensory cortex (S1BF). We find that perfusion of oxytocin onto acute brain slices significantly increases the frequency of miniature excitatory postsynaptic currents (mEPSC) of S1BF L2/3 pyramidal neurons at P10 and P14, but reduces it at the later ages of P22 and P28; the transition occurs at around P18. Since oxytocin expression is itself regulated by sensory experience, we also examine whether the effects of oxytocin on excitatory synaptic transmission correlate with that of sensory experience. We find that, indeed, the effects of sensory experience and oxytocin on excitatory synaptic transmission of L2/3 pyramidal neurons both peak at around P14 and plateau around P18, suggesting that they regulate a specific form of synaptic plasticity in L2/3 pyramidal neurons, with a sensitive/critical period ending around P18. Consistently, oxytocin receptor (Oxtr) expression in glutamatergic neurons of the upper layers of the cerebral cortex peaks around P14. By P28, however, Oxtr expression becomes more prominent in GABAergic neurons, especially somatostatin (SST) neurons. At P28, oxytocin perfusion increases inhibitory synaptic transmission and reduces excitatory synaptic transmission, effects that result in a net reduction of neuronal excitation, in contrast to increased excitation at P14. Using oxytocin knockout mice and Oxtr conditional knockout mice, we show that loss-of-function of oxytocin affects baseline excitatory synaptic transmission, while Oxtr is required for oxytocin-induced changes in excitatory synaptic transmission, at both P14 and P28. Together, these results demonstrate that oxytocin has complex and dynamic functions in regulating synaptic transmission in cortical L2/3 pyramidal neurons. These findings add to existing knowledge of the function of oxytocin in regulating neural circuit development and plasticity.

Low-Calcium Epileptiform Activity in the Hippocampus In Vivo

2003 ◽  
Vol 90 (4) ◽  
pp. 2253-2260 ◽  
Author(s):  
Zhouyan Feng ◽  
Dominique M. Durand
Keyword(s):  
Synaptic Transmission ◽  
Epileptiform Activity ◽  
Brain Slices ◽  
Early Period ◽  
Epileptic Activity ◽  
Slow Waves ◽  
Stratum Radiatum ◽  
Low Calcium

It has been clearly established that nonsynaptic interactions are sufficient for generating epileptiform activity in brain slices. However, it is not known whether this type of epilepsy model can be generated in vivo. In this paper we investigate low-calcium nonsynaptic epileptiform activity in an intact hippocampus. The calcium chelator EGTA was used to lower [Ca2+]o in the hippocampus of urethane anesthetized rats. Spontaneous and evoked field potentials in CA1 pyramidal stratum and in CA1 stratum radiatum were recorded using four-channel silicon recording probes. Three different types of epileptic activity were observed while synaptic transmission was gradually blocked by a decline in hippocampal [Ca2+]o. A short latency burst, named early-burst, occurred during the early period of EGTA application. Periodic slow-waves and a long latency high-frequency burst, named late-burst, were seen after synaptic transmission was mostly blocked. Therefore these activities appear to be associated with nonsynaptic mechanisms. Moreover, the slow-waves were similar in appearance to the depolarization potential shifts in vitro with low calcium. In addition, excitatory postsynaptic amino acid antagonists could not eliminate the development of slow-waves and late-bursts. The slow-waves and late-bursts were morphologically similar to electrographic seizure activity seen in patients with temporal lobe epilepsy. These results clearly show that epileptic activity can be generated in vivo in the absence of synaptic transmission. This type of low-calcium nonsynaptic epilepsy model in an intact hippocampus could play an important role in revealing additional mechanisms of epilepsy disorders and in developing novel anti-convulsant drugs.

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