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PubMed1991

Rhythm generation in brainstem cultures grown in a serum-free medium.

Electrophysiological studies were carried out on long term cultured brainstem tissue taken from neonatal rats with the object of investigating mechanisms underlying respiratory rhythm generation. The preparations were derived from 360 microns thick horizontal medullary slices which were explanted into a chemically defined nutrient medium and which remained organotypically intact for ca. 1 month. In 44 of the 50 explants examined both periodic and aperiodic bioelectric activity was detected, the cycle length of the former ranging from 0.5 to 10 s (mean, 2.7 s) at a pH of 7.4 and bath temperature of 32 degrees C. Periodic activity could take several forms, but commonly consisted of regularly repeated, 100-300 ms long, depolarizing (D-) waves or sequences of inhibitory and/or excitatory postsynaptic potentials. Lowering the pH of the superfusate by lowering the bicarbonate concentration, increasing the pCO2 or adding H+ shortened the interval between periodic events, and increased both the amplitude and duration of the D-waves. The interval was also shortened when the bath temperature was increased (Q10: ca.2.5). The mean resting membrane potential of neurons exhibiting periodic activity was -49 mV (n = 62) and not significantly different from that of aperiodically discharging neurons either in the same preparations or in cultured explants from the neocortex. These observations suggest that brainstem cultures constitute a useful 'model' system for studying pH-dependent rhythm generation in small neuronal networks of the medulla.

Action Potentials↗

PubMed1993

Arachidonic acid inhibits sodium currents and synaptic transmission in cultured striatal neurons.

In the striatum, dopamine generates arachidonic acid (AA) and induces synaptic depression. Here, we report that Na+ channels are a target for AA in both cultured and acutely isolated striatal neurons. AA depressed veratrine-induced Na+ influx and neurotransmitter release. Whole-cell voltage clamp revealed that peak Na+ currents are depressed, and steady-state inactivation shifts -15 mV in the presence of AA. Furthermore, inactivation was accelerated, and recovery from inactivation was delayed. These actions of AA were not produced by AA metabolites or protein kinase C activation. In addition, AA reduced both the amplitude and frequency of action potentials and depressed spontaneous inhibitory postsynaptic currents without affecting miniature inhibitory postsynaptic currents. These data suggest that AA modulates presynaptic, Na(+)-dependent action potentials, thereby contributing to striatal synaptic depression.

Action Potentials↗

PubMed1982

Ethanol in low doses augments calcium-mediated mechanisms measured intracellularly in hippocampal neurons.

The electrophysiological effects of ethanol in low doses (5 to 20 millimoles per liter or 23 to 92 milligrams per 100 milliliters) were examined intracellularly in CA1 cells of rat hippocampus in vitro. Inhibitory and excitatory postsynaptic potentials were increased when ethanol was applied to the respective synaptic terminal regions. Postsynaptically, ethanol caused a moderate hyperpolarization with increased membrane conductance, even when synaptic transmission was blocked. Ethanol augmented the hyperpolarization that followed repetitive firing or that followed the eliciting of calcium spikes in the presence of tetrodotoxin, but not the rapid afterhyperpolarization in calcium-free medium. Ethanol appears to augment calcium-mediated mechanisms both pre- and postsynaptically.

Animals↗

PubMed1995

Excitatory and inhibitory transmission from the optic tectum to nucleus isthmi and its vicinity in amphibians.

Intracellular recordings were made from nucleus isthmi (NI) and its vicinity in toads (Bufo bufo gargarizans) in response to electrical stimulation of the bilateral optic tract. The results suggest that NI mainly receives its excitatory input from the ipsilateral tectum and its inhibitory input from the contralateral tectum. Tegmental cells in a region medioventral to NI were usually characterized by strong spontaneous activity and an excitatory-inhibitory sequence of postsynaptic potentials in response to stimulation of either side of the bilateral optic tract. Sixty of the recorded cells were stained with Lucifer yellow to show their morphological features and anatomical positions within NI and its vicinity.

Animals↗

PubMed1982

Actions of avermectin B1a on GABA nerves.

Avermectin B1a (AVM) is a macrolide derived from Streptomyces avermitilis. It possesses potent anthelmintic and insecticidal activities. It immobilizes nematodes by blocking the signal transmission from the central command interneurons to the peripheral motoneurons; this block can be reversed by the chloride ion channel blocker picrotoxin. The arthropods are paralyzed by AVM through drug inhibition of both inhibitory and excitatory postsynaptic potentials at the neuromuscular junctions. The mechanism of action is reduction of the muscle membrane resistance by opening the gamma-aminobutyric acid (GABA)-controlled chloride ion channels in the membrane--an action also inhibitable by picrotoxin. AVM has specific and high-affinity binding sites in the mammalian brain synaptic membrane. The sites are concentrated in the cerebellum and closely associated with the GABA-benzodiazepine receptor-chloride ion channel complex. GABA release from brain synaptosomes is specifically stimulated by AVM. The density of available postsynaptic GABA receptors is increased by AVM--a process which requires chloride ion and is inhibited by picrotoxin. AVM also stimulates benzodiazepine binding and potentiates the in vivo diazepam activity of muscle relaxation. These findings add up to a conclusive demonstration of the mechanism of AVM action as a potentiation of the GABA action. They also point out the research on GABA nerve in invertebrates as an attractive approach to chemotherapy against nematodes and insects and suggest AVM as a very useful tool in isolating GABA receptors and in-depth understanding of GABA function.

Animals↗

PubMed1990

Inhibitory innervation of a lobster muscle.

Inhibitory neuromuscular synapses formed by the common inhibitor (CI) neuron on the distal accessory flexor muscle (DAFM) in the lobster, Homarus americanus, were studied with electrophysiological and electron-microscopic (thin-section and freeze-fracture) techniques. Postsynaptic inhibition as indicated by inhibitory junctional potentials was several-fold stronger on distal compared to proximal muscle fibers. This difference correlated with the results of serial thin-section studies, which showed more inhibitory synapses on distal fibers than on their proximal counterparts. Effects of postsynaptic inhibition on excitatory junctional potentials via current shunting had a morphological correlate in the spatial relationship between inhibitory and excitatory synapses on the distal fibers. Inhibitory synapses were larger than their excitatory counterparts and had fewer glial processes. In freeze-fracture views, inhibitory synapses did not appear as raised plateaus in the P-face as do excitatory synapses, and their active zones were more widely scattered. The intramembrane particles in the inhibitory postsynaptic membrane - representing neurotransmitter receptors - are arranged in parallel rows in the sarcolemmal P-face and have complementary furrows in the sarcolemmal E-face. Altogether, our findings help to describe a population of inhibitory neuromuscular synapses formed by the CI neuron in lobster muscle.

Action Potentials↗

PubMed2004

Functional properties of electrical synapses between inhibitory interneurons of neocortical layer 4.

The existence of electrical synapses between GABAergic inhibitory interneurons in neocortex is well established, but their functional properties have not been described in detail. We made whole cell recordings from pairs of electrically coupled fast-spiking (FS) or low threshold-spiking (LTS) neurons, and filled some cells with biocytin for morphological reconstruction. Data were used to create compartmental cable models and to guide mathematical analysis. We analyzed the time course and amplitude of electrical postsynaptic potentials (ePSPs), the subthreshold events generated by presynaptic action potentials, in both FS and LTS neurons. The results imply that the generation of ePSPs is predominantly a linear process in both cell types for presynaptic firing of both single and repetitive spikes. Nonlinearities shape ePSPs near spike threshold, but our data suggest that the underlying synaptic current is still a linear process. Cell-to-cell electrical signaling on longer timescales also appears to be linear. Cable models of electrically coupled FS and LTS neurons imply that the analyzed electrical synapses are, on average, within 50 mum of the soma. Finally, we show that electrical coupling between 2 inhibitory cells promotes synchrony at all spiking frequencies. This contrasts with the effect of reciprocal inhibitory postsynaptic potentials (IPSPs) evoked by the same cells, which promote antisynchronous firing at frequencies less than about 100 Hz. Electrical coupling counteracts the antisynchronous behavior induced by IPSPs and facilitates spiking synchrony. Our results suggest that electrical synapses among inhibitory interneurons are most readily described as low-pass linear filters that promote firing synchrony.

Analysis of Variance↗

PubMed2006

TRPV1 receptor mediates glutamatergic synaptic input to dorsolateral periaqueductal gray (dl-PAG) neurons.

The purpose of this study was to determine the role of transient receptor potential vanilloid type 1 (TRPV1) receptor in modulating neuronal activity of the dorsolateral periaqueductal gray (dl-PAG) through excitatory and inhibitory synaptic inputs. First, whole cell voltage-clamp recording was performed to obtain the spontaneous miniature excitatory postsynaptic currents (mEPSCs) and inhibitory postsynaptic currents (mIPSCs) of the dl-PAG neurons. As 1 microM of capsaicin was applied into the perfusion chamber, the frequency of mEPSCs was increased from 3.21 +/- 0.49 to 5.64 +/- 0.64 Hz (P < 0.05, n = 12) without altering the amplitude and the decay time constant of mEPSCs. In contrast, capsaicin had no distinct effect on mIPSCs. A specific TRPV1 receptor antagonist, iodo-resiniferatoxin (i-RTX, 300 nM), decreased the frequency of mEPSCs from 3.51 +/- 0.29 to 2.01 +/- 0.2 Hz (P < 0.05, n = 8) but did not alter the amplitude and decay time. In addition, i-RTX applied into the chamber abolished the effect of capsaicin on mEPSC of the dl-PAG. In another experiment, spontaneous action potential of the dl-PAG neurons was recorded using whole cell current-clamp methods. Capsaicin significantly elevated the discharge rate of the dl-PAG neurons from 3.03 +/- 0.38 to 5.96 +/- 0.87 Hz (n = 8). The increased firing activity was abolished in the presence of glutamate N-methy-D-aspartate (NMDA) and non-NMDA antagonists, 2-amino-5-phosphonopentanoic acid, and 6-cyano-7-nitroquinoxaline-2,3-dione. The results from this study provide the first evidence indicating that activation of TRPV1 receptors increases the neuronal activity of the dl-PAG through selective potentiation of glutamatergic synaptic inputs.

Action Potentials↗

PubMed1999

Saccade-related inhibitory input to pontine omnipause neurons: an intracellular study in alert cats.

Omnipause neurons (OPNs) are midline pontine neurons that are thought to control a number of oculomotor behaviors, especially saccades. Intracellular recordings were made from OPNs in alert cats to elucidate saccade-associated postsynaptic events in OPNs and thereby determine what patterns of afferent discharge impinge on OPNs to cause their saccadic inhibition. The membrane potential of impaled OPNs exhibited steep hyperpolarization before each saccade that lasted for the whole period of the saccade. The hyperpolarization was reversed to depolarization by intracellular injection of Cl- ions, indicating it consisted of temporal summation of inhibitory postsynaptic potentials (IPSPs). The duration of the saccade-related hyperpolarization was almost equal to the duration of the concurrent saccades. The time course of the hyperpolarization was similar to that of the radial eye velocity except for the initial phase. During the falling phase of eye velocity, the correlation between the instantaneous amplitude of hyperpolarization and the instantaneous eye velocity was highly significant. The amplitude of hyperpolarization at the eye velocity peak was correlated significantly with the peak eye velocity. The time integral of the hyperpolarization was correlated with the radial amplitude of saccades. The initial phase disparity between the hyperpolarization and eye velocity was due to the relative constancy of peak time (approximately 20 ms) of the initial steep hyperpolarization regardless of the later potential profile that covaried with the eye velocity. The initial steep hyperpolarization led the beginning of saccades by 15.9 +/- 3.8 (SD) ms, which is longer than the lead time for medium-lead burst neurons. These results demonstrate that the pause of activity in OPNs is caused by IPSPs initiated by an abrupt, intense input and maintained, for the whole duration of the saccade, by afferents conveying eye velocity signals. We suggest that the initial sudden inhibition originates from central structures such as the superior colliculus and frontal eye fields and that the eye velocity-related inhibition originates from the burst generator in the brain stem.

Animals↗

PubMed1997

Stimulation within the rostral ventrolateral medulla can evoke monosynaptic GABAergic IPSPs in sympathetic preganglionic neurons in vitro.

The inhibitory responses of identified sympathetic preganglionic neurons (SPNs) to stimulation within the rostral ventrolateral medulla (RVLM) were studied to determine their nature and pharmacology. Whole cell patch-clamp recordings were made from 36 SPNs in the upper thoracic segments of the spinal cord in a neonatal rat brain stem-spinal cord preparation. Neurons were identified as SPNs on the basis of their antidromic activation after stimulation of the ipsilateral segmental ventral root and their morphology and location in the intermediolateral cell column and intercalated nucleus. In all SPNs, electrical stimulation of the RVLM evoked fast excitatory postsynaptic potentials (EPSPs) that were mediated by non-N-methyl-D-aspartate (NMDA) and NMDA receptors. These excitatory responses were the most prominent response in control artificial cerebrospinal fluid and have been studied previously. In 22 of the SPNs, RVLM stimulation also elicited fast inhibitory postsynaptic potentials (IPSPs), which increased in amplitude as the membrane was depolarized. Five of these neurons were not studied further as they responded occasionally with IPSPs that had highly variable onset latencies indicating the involvement of a polysynaptic pathway. In the remaining SPNs (n = 17), the evoked IPSPs persisted in the presence of the excitatory amino acid antagonists 6-cyano-7-nitroquinoxaline-2,3,-dione and D,L-2-amino-5-phosphonopentanoic acid. In eight of these SPNs, it was necessary to block the EPSPs to reveal the IPSPs. In the 7 SPNs tested, the onset latencies of the IPSPs were not significantly different from the onset latencies of the fast EPSPs. The low sweep-to-sweep fluctuations in onset latency of individual IPSPs (absolute average deviation: 0.4 ms) indicated that the IPSPs were elicited by activation of a monosynaptic pathway. The amplitudes of the IPSPs decreased in amplitude as the membrane was hyperpolarized and reversed in polarity at -70.3 +/- 1.7 mV (mean +/- SD), which was close to the equilibrium potential for chloride ions. In addition, in seven SPNs, bath applications of 5 microM bicuculline, a gamma-aminobuturic acid-A (GABAA) antagonist, abolished or reduced the evoked IPSPs. Five SPNs also were studied that displayed ongoing IPSPs. The amplitudes of these IPSPs increased with membrane depolarization and were blocked by bath applications of 5 microM bicuculline, suggesting that they also were mediated by activation of GABAA receptors. These results demonstrate the existence of a bulbospinal GABAergic pathway impinging directly onto SPNs. This pathway may be tonically active in the neonatal rat brain stem-spinal cord preparation.

Adrenergic Fibers↗

PubMed1982

Inhibitory modulation of long-term potentiation: evidence for a postsynaptic locus of control.

Long-term potentiation (LTP) of the excitatory synapses of the perforant path onto the granule cells of the fascia dentata was prevented, or greatly reduced in amount, by stimulation of the contralateral hilus, a source of the commissural afferents and an indirect source of granule cell inhibition. The LTP was reduced only when the onset of contralateral stimulation fell within 50 ms before and 1 ms after the onset of the perforant path conditioning train. Over this time interval, the ability of the volley from the contralateral hilus to block granule cell discharge (population spike) caused by the perforant path conditioning train varied, but not with a time course corresponding to the reduction of LTP. Although trains of impulses applied at high frequency (3-8 pulses at 400 Hz) were often able to block the perforant path LTP completely, single shocks strong enough to block the perforant path population spike were not sufficient to reduce LTP. The results support Marr's proposal that local inhibitory networks may set the threshold for producing long-term synaptic modification. They do not support Hebb's nor Uttley's proposal since the long-term synaptic modification did not depend on either the occurrence or the absence of a postsynaptic action potential.U

Anesthesia, General↗

PubMed1992

Single local interneurons in the locust make central synapses with different properties of transmitter release on distinct postsynaptic neurons.

Quantal analysis has been applied to the inhibitory synapses made by single spiking local interneurons onto several nonspiking local interneurons (and motorneurons) in the locust CNS. Transmission at these synapses appears to be mediated by GABA. The apparent reversal potential of the IPSP and inhibitory postsynaptic current were -80 to -85 mV, a value similar to that of the potential evoked by pressure-applied GABA. This reversal potential was 25-30 mV more negative than the resting potential of the nonspiking interneurons in the experimental conditions. The statistical properties of release at these synapses were studied by recording simultaneously from pre- and postsynaptic interneurons with intracellular electrodes. The distribution of postsynaptic potential amplitudes could be described by a simple binomial model, implying uniformity of binomial p (probability of release at a single release site) for each synapse. The mean quantal amplitude was 290 +/- 110 microV, and the mean quantal content m of the IPSPs was 6.25 +/- 2.83. The mean values of binomial n (average size of the releasable pool) and p were 13.11 +/- 2.8 and 0.45 +/- 0.16, respectively. Numerical simulations of statistical experiments were performed to test whether the IPSP amplitude distribution histograms might be misleadingly indicative of quantal release. These simulations showed that such a hypothesis was very unlikely. When a spiking local interneuron was impaled, several of its target interneurons could sometimes be successively sampled. Quantal analysis was then performed with the different IPSPs evoked, in identical conditions, by a same presynaptic interneuron, and the quantal parameters were compared between the synapses. It was found that binomials n and p and their product m generally differed between the synapses made by a given spiking interneuron onto different target neurons. These results show that quantal contents can vary for the many synapses made centrally by one interneuron, and suggest that this variability may arise from differences in release probabilities between the sites associated with different synapses.

Animals↗

PubMed1992

Opioid inhibition of GABA release from presynaptic terminals of rat hippocampal interneurons.

Opiates and the opioid peptide enkephalin can cause indirect excitation of principal cortical neurons by reducing inhibitory synaptic transmission mediated by GABAergic interneurons. The mechanism by which opioids mediate these effects on interneurons is unknown, but enkephalin hyperpolarizes the somatic membrane potential of a variety of neurons in the brain, including hippocampal interneurons. We now report a new, more direct mechanism for the opioid-mediated reduction in synaptic inhibition. The enkephalin analog D-Ala2-Met5-enkephalinamide (DALA) decreases the frequency of miniature, action potential-independent, spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) without causing a change in their amplitude. Thus, we conclude that DALA inhibits the action potential-independent release of GABA through a direct action on interneuronal synaptic terminals. In contrast, DALA reduces the amplitude of action potential-evoked, GABA-mediated IPSCs, as well as decreases their frequency. This suggests that the opioid-mediated inhibition of non-action potential-dependent GABA release reveals a mechanism that contributes to reducing action potential-evoked GABA release, thereby decreasing synaptic inhibition.

Action Potentials↗

PubMed2006

Neuropeptide Y and corticotropin-releasing factor bi-directionally modulate inhibitory synaptic transmission in the bed nucleus of the stria terminalis.

Neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) have opposing effects on stress and anxiety. Both can modify synaptic activity through their binding to NPY receptors (YRs) and CRF receptors (CRFRs) respectively. The bed nucleus of the stria terminalis (BNST) is a brain region with enriched expression of both NPY and YRs and CRF and CRFRs. A component of the "extended amygdala", the BNST is anatomically well-situated to integrate stress and reward-related processing in the CNS, regulating activation of the hypothalamic-pituitary-adrenal (HPA) axis and reward circuits. Using whole-cell recordings in a BNST slice preparation, we found that NPY and CRF inhibit and enhance GABAergic transmission, respectively. Pharmacological experiments suggest that NPY depresses GABAergic transmission through activation of the Y2 receptor (Y2R), while both pharmacological and genetic experiments suggest that CRF and urocortin enhance GABAergic transmission through activation of the CRF receptor 1 (CRFR1). Further, the data suggest that NPY acts to regulate GABA release, while CRF enhances postsynaptic responses to GABA. These results suggest potential anatomical and cellular substrates for the robust behavioral interactions between NPY and CRF.

Analysis of Variance↗

PubMed1997

Noradrenaline modulates glutamate-mediated neurotransmission in the rat basolateral amygdala in vitro.

The entorhinal cortex and the amygdala are interconnected structures of the limbic system in which paroxysmal activity occurs during temporal lobe epilepsy. Conflicting evidence shows that noradrenaline (i) inhibits the spreading to other parts of the limbic system of paroxysmal activity generated in the amygdala or the entorhinal cortex, but also (ii) increases glutamatergic transmission in the basolateral amygdala. Given our previous work on the inhibitory effect of noradrenaline on entorhinal cortex neurons, we developed an in vitro slice preparation to study the synaptic transmission in the basolateral amygdala and its modulation by noradrenaline. Noradrenaline reduced the fast excitatory postsynaptic potential (EPSP) by approximately 40% at 100 microM and the slow EPSP by approximately 50% at 50 microM. A similar effect was obtained with the alpha2-agonist UK 14304 at 100 and 50 microM respectively. In contrast, the beta-agonist isoproterenol increased the fast EPSP by approximately 40% at 100 microM and the slow EPSP by approximately 20% at 50 microM. Accordingly, the effect of noradrenaline on the EPSPs was blocked by the alpha2-antagonist yohimbine (10 microM) but not by the alpha1-antagonist prazosine (10 microM) and the beta-antagonist propranolol (10 microM). Noradrenaline (50-100 microM) was ineffective on most (14/16) of the isolated inhibitory postsynaptic potentials (IPSPs). These experiments provide evidence that noradrenaline inhibits the excitatory synaptic response of basolateral amygdala neurons. A pharmacological analysis revealed that the noradrenergic modulation of the excitatory transmission in the basolateral amygdala can be dissected into a predominant alpha2-adrenoreceptor-mediated inhibition and a beta-adrenoreceptor-mediated excitation.

Amygdala↗

PubMed1981

Presynaptic inhibitory effect of acetylcholine in the hippocampus.

(1) In order to investigate the effects of acetylcholine (ACh) on synaptic transmission in the rat hippocampus, extracellular and intracellular recordings were made from pyramidal neurons in an in vitro slice preparation while synaptic inputs to the cell population were stimulated. ACh was applied ionophoretically into somatic and dendritic layers of the slice. (2) ACh applied into the apical dendritic layer of the CA1 region reduced the size of the locally evoked field excitatory postsynaptic potential (EPSP) without altering the size of the afferent fiber volley. Likewise, dendritically applied ACh reduced the size of intracellularly recorded EPSPs. This effect of ACh appeared to be muscarinic since it was not affected by hexamethonium (up to 3 X 10-5 M) but was antagonized by atropine in a dose-dependent manner. (3) The distribution of Ach-sensitive sites matched closely the spatial distribution of activated synapses on the pyramidal cell dendrites as shown by ionophoretic mapping experiments. (4) In contrast to the effects of dendritic applications of ACh, ionophoresis of ACh into the cell layer resulted in an increase and prolongation of EPSPs and a transient decrease in the size of recurrent somatic inhibitory postsynaptic potentials (IPSPs). These effects on synaptic potentials could not be explained by the observed changes in membrane potential and input resistance following somatic application of ACh. (5) Short dendritic applications of ACh had no consistent effect on the membrane potential or slope conductance of pyramidal neurons and did not attenuate the depolarization evoked by brief dendritic applications of glutamate. In addition, the time course of ACh-reduced EPSPs was not different from control. (6) We conclude that ACh exerts a presynaptic inhibitory effect on both excitatory and inhibitory afferents to hippocampal pyramidal neurons. This effect of ACh is widespread, occurring in all regions of Ammon's horn tested as well as in stratum moleculare of fascia dentata.

Acetylcholine↗

PubMed2003

Endogenous nitric oxide modulates GABAergic transmission to granule cells in adult rat cerebellum.

Nitric oxide (NO) is a gaseous neurotransmitter which plays an important role in neuronal signalling and plasticity throughout the brain. In the cerebellum, NO synthase (NOS) is expressed in parallel fibres and within the internal granule cell layer (IGL). During development there are changes in NOS concentration, distribution and activity within the IGL, suggesting NO may play a role in IGL function. Therefore, the actions of NO in the IGL were investigated. The similar actions of a range of NOS inhibitors and NO scavengers strongly suggested the presence of a tonic level of endogenous NO in the IGL. Both the neuronal and inducible forms of NOS appeared to be sources of this endogenous NO. The effects observed following a reduction in the concentration of endogenous NO were consistent with enhanced granule cell GABAA receptor activation. For example, a reduction in NO concentration led to an increase in the frequency of action potential-dependent phasic GABAergic inhibitory postsynaptic currents (IPSCs) and produced a TTX-insensitive GABAA receptor-mediated current. A direct action of NO on Golgi cell membrane potential and input resistance accounted for the increase in the frequency of phasic GABA release. The mechanism underlying the tonic GABA current is unclear but does not appear to be via the modulation of GABA uptake or the activation of nicotinic acetylcholine receptors. NO is a potentially novel mechanism for tuning GABAergic signalling to granule cells and therefore modulating the throughput of an important cerebellar circuit.

Animals↗

PubMed2006

Simultaneous NMDA-dependent long-term potentiation of EPSCs and long-term depression of IPSCs in cultured rat hippocampal neurons.

A fundamental issue in understanding activity-dependent long-term plasticity of neuronal networks is the interplay between excitatory and inhibitory synaptic drives in the network. Using dual whole-cell recordings in cultured hippocampal neurons, we examined synaptic changes occurring as a result of a transient activation of NMDA receptors in the network. This enhanced transient activation led to a long-lasting increase in synchrony of spontaneous activity of neurons in the network. Simultaneous long-term potentiation of excitatory synaptic strength and a pronounced long-term depression of inhibitory synaptic currents (LTDi) were produced, which were independent of changes in postsynaptic potential and Ca2+ concentrations. Surprisingly, miniature inhibitory synaptic currents were not changed by the conditioning, whereas both frequency and amplitudes of miniature EPSCs were enhanced. LTDi was mediated by activation of a presynaptic GABAB receptor, because it was blocked by saclofen and CGP55845 [(2S)-3-{[(15)-1-(3, 4-dichlorophenyl)ethyl]amino-2-hydroxypropyl)(phenylmethyl)phosphinic acid]. The cAMP antagonist Rp-adenosine 3 ', 5 ' -cyclic monophosphothioate abolished all measured effects of NMDA-dependent conditioning, whereas a nitric oxide synthase inhibitor was ineffective. Finally, network-induced plasticity was not occluded by a previous spike-timing-induced plasticity, indicating that the two types of plasticity may not share the same mechanism. These results demonstrate that network plasticity involves opposite affects on inhibitory and excitatory neurotransmission.

2-Amino-5-phosphonovalerate↗