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Sodium valproate decreases synaptic potentiation and epileptiform activity in hippocampus.

The actions of sodium valproate (NaVP) were studied in the in vitro hippocampus using extracellular, intracellular and voltage-clamp recording techniques. In the CA1 region, concentrations of 30-200 microM NaVP reduced the amplitude but not the time course of post-tetanic potentiation (PTP) of dendritic field excitatory postsynaptic potentials (EPSPs). Epileptiform discharges were studied intracellularly in CA3 cells after pharmacological blockade of synaptic inhibition and repeated tetanic stimulation. NaVP (100 microM) blocked evoked paroxysmal depolarizing shift (PDS) discharges through a mechanism of increasing the threshold for burst-firing. When the PDS current was studied under voltage-clamp, application of NaVP (100 microM) resulted in a graded reduction of the PDS waveform. All of the actions of NaVP may result from inhibition of excitatory synaptic transmission following repetitive cell firing. A hypothesis is proposed that NaVP may act to decrease excitatory synaptic potentiation necessary for network synchronization.

Action Potentials↗

Non-cholinergic synaptic potentials mediated by lumbar colonic nerve in the guinea-pig inferior mesenteric ganglion in vitro.

Non-cholinergic slow synaptic potentials mediated by the lumbar colonic nerve have been investigated using an in vitro preparation of the guinea-pig inferior mesenteric ganglion attached to a distal colonic segment. Non-cholinergic potential responses to colonic nerve stimulation, colonic distension and chemical activation of sensory afferents were recorded intracellularly from neurons in the inferior mesenteric ganglion. Electrical stimulation of the lumbar colonic nerve produced either a slow excitatory postsynaptic potential, or a slow inhibitory postsynaptic potential followed by a slow excitatory postsynaptic potential. The extrapolated reversal potential of the slow excitatory postsynaptic potential was in the range of 0 to -20 mV and that of the slow inhibitory postsynaptic potential was -90 to 110 mV. The slow excitatory postsynaptic potential and the slow inhibitory postsynaptic potential were reversibly abolished by perfusion of the ganglion with tetrodotoxin (1 microM), or perfusion with low calcium (200 microM), high magnesium (12 mM) containing solution. Capsaicin (1 microM) evoked a reversible depolarization of inferior mesenteric ganglion cells after which desensitization occurred and the slow excitatory postsynaptic potential was abolished but the slow inhibitory postsynaptic potential was enhanced in amplitude and prolonged in duration. Bath application of substance P (2 microM) evoked a prolonged depolarization of inferior mesenteric ganglion neurons, during which the slow excitatory postsynaptic potential but not the slow inhibitory postsynaptic potential was abolished. Distensions of the colon to pressures in the range of 2-25 cm of water produced a stimulus graded non-cholinergic slow depolarization which was occasionally followed by a late slow hyperpolarization. Both types of response were abolished by tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Post-synaptic potentials in a population of motoneurones following activity of single interneurones in the cat.

The technique of recording post-synaptic potentials from a population of motoneurones, by recording from ventral roots perfused with isotonic sucrose, has been applied to investigate the action of single last-order interneurones; the target motoneurones were in either caudal L7 or S1 segments. Using spike-triggered averaging, the inhibitory action of 70% of previously identified last-order interneurones (Renshaw cells and lamina VII Ia inhibitory interneurones) has been detected. Previous observations had suggested that interneurones mediating disynaptic non-reciprocal inhibition from group I muscle afferents should be characterized by (i) location in laminae V-VI, (ii) monosynaptic group I input and (iii) ascending collateral axonal projection to upper lumbar segments. 65% of interneurones with these characteristics were found to inhibit motoneurones. In addition, spike-triggered averaging from this group of laminae V-VI interneurones sometimes revealed a depolarizing potential which preceded the inhibitory potential evoked by the interneurone. The depolarizing potential is interpreted as being due to the action of some presynaptic fibres which branch to innervate both the investigated interneurones and motoneurones.

Animals↗

Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice cultures.

1. The effects of the gamma-aminobutyric acid (GABA) uptake blocker tiagabine on inhibitory synaptic potentials (IPSPs) were examined with microelectrode and whole-cell recording from CA3 pyramidal cells in rat hippocampal slice cultures. 2. Tiagabine (10-25 microM) greatly prolonged the duration of monosynaptic IPSPs elicited in the presence of excitatory amino acid antagonists but had no effect on their amplitude. Part of the prolonged time course resulted from a GABAB receptor-mediated component that was not detectable under control conditions. 3. The mean decay time constant of the underlying GABAA receptor-mediated synaptic current was increased from 16 to 250 ms. Spontaneous miniature IPSPs recorded with whole-cell clamp were unaffected by tiagabine. Pentobarbital sodium, in contrast, increased the decay time constant of both evoked and spontaneous GABAA-mediated currents. 4. Tiagabine (25 microM) inhibited spontaneous and evoked epileptiform bursting induced by increasing the extracellular potassium concentration to 8 mM. 5. We conclude that GABA uptake plays a significant role in determining the time course of evoked IPSPs and also limits the likelihood that GABAB receptors are activated.

Animals↗

Reduced Mg2+ block of N-methyl-D-aspartate receptor-mediated synaptic potentials in developing visual cortex.

Molecular cloning has demonstrated a diversity of artificially expressed N-methyl-D-aspartate (NMDA) receptors, implying a similar diversity of naturally occurring NMDA receptors in situ. Particularly significant was the success in expression of NMDA receptor classes exhibiting various sensitivities to Mg2+ block, a voltage-dependent channel blockade by Mg2+ that is essential to NMDA receptor functioning. Release from Mg2+ block often allows or facilitates the occurrence of long-term potentiation, a form of synaptic plasticity. Here we show that in the immature visual cortex, which is more susceptible to long-term potentiation than adult visual cortex, synaptically activated NMDA receptors, unlike those in the adult, have varying but clearly reduced sensitivities to Mg2+ block. We propose that the initially expressed, later-eliminated NMDA receptors exhibiting a reduced Mg2+ block may underlie the greater susceptibility to plasticity in the immature neocortex.

Age Factors↗

Dendritic attenuation of synaptic potentials in the CA1 region of rat hippocampal slices detected with an optical method.

We directly measured fast excitatory postsynaptic potentials (EPSPs) along the dendrites of hippocampal CA1 pyramidal neurons by employing an optical method to study how synaptic potentials spread along the dendrites. Rat hippocampal slices were stained with a fluorescent voltage-sensitive dye JPW1114 and optical signals were monitored with a 16 x 16 photodiode array system. A stimulating electrode was placed either at stratum lacunosum moleculare to activate perforant fibers that make synaptic contacts to the distal apical dendrites or at stratum oriens to induce EPSPs at the basal dendrites of CA1 pyramidal cells. CNQX-sensitive components of the optical signals, which were assumed to be population EPSPs, were isolated. Propagation and attenuation of the CNQX components were successfully observed with the optical method. At the cell body layer, the peak of the CNQX-sensitive component was delayed by 17.08 +/- 1.64 ms from the input sites. Additionally we performed a simulation study to estimate the passive membrane parameters of the apical dendrites. Estimated apparent specific internal axial resistance (Ri) following stratum lacunosum moleculare stimulation was 76.0 +/- 4.2 Omega.cm and apparent specific membrane resistance (Rm) was 27.8 +/- 2.1 kOmega.cm2 (assuming the specific membrane capacitance of dendrites Cm = 1.6 microF/cm2). These values are comparable to those previously reported. When synaptic inputs were applied at stratum oriens, these apparent passive membrane parameters were different (high Ri and low Rm), suggesting that nonuniform dendritic membrane conductance or voltage-dependent conductances which are active near the resting potential may contribute to the measured passive membrane properties.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

A caged Ab reveals an immediate/instructive effect of BDNF during hippocampal synaptic potentiation.

Neurotrophins have been shown to be involved in functional strengthening of central nervous system synapses. Although their general importance in this process is undisputed, it remains unresolved whether neurotrophins are truly mediators of synaptic strengthening or merely important cofactors. To address this question, we have devised a method to inactivate endogenous brain-derived neurotrophic factor (BDNF) with high time resolution by "caging" a function-blocking mAb against BDNF with a photosensitive protecting compound. Different assays were used to show that this inactivation of the Ab is reversible by UV light. Synaptic potentiation after theta-burst [corrected] stimulation in the CA1 region of acute hippocampal slices was significantly less when applying the unmodified Ab compared with the caged Ab. Importantly, photoactivation of the caged Ab during the time of induction of synaptic enhancement led to a marked decrease in potentiation. Our experiments therefore strengthen the view that endogenous BDNF has fast effects during induction of synaptic plasticity. The results additionally show that caged Abs can provide a tool for precise spatiotemporal control over endogenous protein levels.

Animals↗

[Antidromal and synaptic potentials of motoneurons of the cat accessory nerve nucleus].

Field potentials were recorded in segments C1-C4 after stimulation of n. accessorius. In this region antidromic and synaptic potentials 20 n. accessory motoneurons were recorded. They were produced by stimulation of the accessory nerve and other peripheral nerves. The latency of antidromic potentials was 0.6-1.1 ms. Only EPSPs and action potentials were produced by stimulation of different peripheral nerves. EPSP's latency were 2.2-4.4 ms for the third cervical nerve, 3.8-5.8 ms for n. splenius, 11-20 ms for n. radialis superficialis, 2.2-3.5 ms for n. infraorbitalis.

Accessory Nerve↗

[Effect of calcium deficiency and addition of calcium antagonists on motoneuron synaptic potentials of isolated Emys orbicularis turtle spinal cord].

In experiments carried out on the isolated spinal cord of the tortoise Emys orbicularis postsynaptic potentials produced in spinal motoneurons by stimulation of the descending tracts and dorsal roots were investigated by means of the intracellular recording technique. Postsynaptic potentials were completely and reversibly blocked in Ca2+-free solutions containing 5.0 mM Mg2+ or 2.0 mM Mn2+. The amplitude and frequency of spontaneous synaptic potentials were also reduced under these conditions. The effect of Ca2+-free medium indicates that the synaptic transmission in these synapses is mediated by chemical mechanism.

Animals↗

An apparatus for recording synaptic potentials from neuronal cultures using voltage-sensitive fluorescent dyes.

Voltage-sensitive dyes offer the promise of noninvasive multicell recording of electrical activity, and should therefore be useful for studying the synaptic interactions of small networks of cultured neurons. We have designed and built a system for recording from microcultures of 1-15 neurons from the rat superior cervical ganglion (SCG), using voltage-sensitive fluorescent dyes of the styryl class. The apparatus comprises a standard inverted epifluorescence microscope; a mercury arc lamp with an optical feedback regulator; a 256-pixel fiber-optic camera with individual photodiode detectors and very low-noise amplifiers; and a personal computer-based data acquisition system. Its dark noise and illumination fluctuations are low enough that at typical fluorescence levels for these cells, it is limited by shot noise (the inherent physical limit of detection). Recording from SCG neurons, the signal-to-noise ratio is high enough to see large subthreshold synaptic potentials without signal averaging. This apparatus should be useful for studying long-term synaptic plasticity in cultures of vertebrate neurons, and several of its features should apply to optical recording from other preparations.

Analog-Digital Conversion↗

Inhibition by sodium bromide of synaptic potentiation and calcium accumulation in the superior cervical ganglion of rat.

Electrophysiological data show that sodium bromide (NaBr) inhibits the development of the post-tetanic potentiation in superior cervical ganglia of rat. NaBr treatment also prevented the accumulation of calcium in synaptic vesicles and dendritic vacuoles otherwise seen for some minutes after a tetanizing stimulation. These observations support the notion that the calcium ions entering into pre- and postsynaptic elements play an important role in the genesis of synaptic potentiation.

Animals↗

Glycolysis regulates the induction of lactate utilization for synaptic potentials after hypoxia in the granule cell of guinea pig hippocampus.

Lactate is considered an alternative substrate that is capable of replacing glucose in maintaining synaptic function in adult neurons. But, we found recently that lactate could be utilized for maintenance of synaptic potentials only after the activation of NMDA and voltage-dependent-calcium channel during glucose deprivation. To clarify more on the relationship between glycolysis and induction of lactate utilization, we tested lower concentration of glucose with hypoxia to induce a relative shortage of anaerobic energy production. Population spikes are not maintained with lactate following hypoxia in 10 mM glucose medium, but are maintained at their original levels with lactate after exposure to hypoxia in lower concentration (5 mM) of glucose. Hypothermia during low glucose-hypoxia, bath application of the NMDA channel blocker and the voltage-sensitive calcium channel blocker, as well as the omission of extracellular calcium prevented the induction of the lactate-supported population spikes. ATP levels in the tissue slices are relatively preserved in the conditions that block the induction of lactate-supported population spikes. From these observations, we propose that the energy source for maintenance of synaptic function in adult neuron changes from adult form (glucose alone) to immature one (glucose and/or lactate) after short of glucose supply.

Action Potentials↗

Long-term depression in the hippocampal CA1 region is associated with equal changes in AMPA and NMDA receptor-mediated synaptic potentials.

In the CA1 hippocampal region low-frequency (1-2 Hz) afferent activation leads to a long-term depression of excitatory synaptic potentials that is induced by calcium influx through postsynaptic N-methyl-D-aspartate receptor channels. In the present experiments using 2- to 3-week-old rats, long-term depressions of field excitatory postsynaptic potentials mediated by amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and by N-methyl-D-aspartate receptor channels were examined in parallel, using a perfusion solution containing low concentrations of an AMPA receptor antagonist and of magnesium (0.1 mM). These experiments revealed that long-term depression was associated with equal relative changes in the two components of the field potential, compatible with a presynaptic location of the expression mechanism for the long-term depression.

Animals↗

Evoked slow muscarinic acetylcholinergic synaptic potentials in rat hippocampal interneurons.

The hippocampus receives an extensive cholinergic input from the medial septal nucleus that ramifies throughout all layers and plays a pivotal modulatory role in cognitive function. Although the pharmacological effects of exogenous application of cholinergic agonists have been extensively studied in hippocampal neurons, much less is known about the effects of synaptically released acetylcholine (ACh). In this respect, most studies have focused on the cholinergic afferent input to pyramidal neurons that produces a characteristically slow depolarizing synaptic response mediated by activation of muscarinic ACh receptors (mAChRs). Here we report that cholinergic afferent stimulation also elicits atropine-sensitive synaptic potentials in hippocampal CA1 interneurons but, in contrast to synaptic responses in pyramidal neurons, these are highly diverse in waveform, although can still be classified into five distinct subtypes. The most common response type (i) 64% of cells) consisted of a slow sustained membrane potential depolarization. The other 36% of responses could be subdivided into responses comprising of (ii) a biphasic membrane potential change in which an initial slow hyperpolarization subsequently transforms into a slow depolarization (20%), (iii) a pure, slow hyperpolarization (13%), and (iv) an oscillatory response persisting for several seconds (2%). Interestingly, there were also interneurons totally insensitive to both synaptic and pharmacological cholinergic challenge. Morphological investigation of recorded cells revealed no obvious correlation between responsiveness to cholinergic afferent stimulation and dendritic and axonal arborization. The current study suggests that synaptic release of ACh results in a complex and differential mAChR-mediated modulation of cellular excitability within the hippocampal interneuron population.

Acetylcholine↗

Differences between steady-state and transient post-synaptic potentials elicited by stimulation of the sural nerve.

In cat medial gastrocnemius motoneurons, single stimuli to the cutaneous sural nerve evoke a post-synaptic potential with a mixture of depolarization and hyperpolarization, depolarization being dominant in type F cells and hyperpolarization in type S cells. This pattern is consistent with previous reports showing that activation of the sural nerve can sometimes reverse the normal order of motor unit recruitment by inhibiting S motor units while simultaneously exciting F motor units. However, during repetitive stimulation for 1-2 s, we found that the hyperpolarizing component of the sural input to medial gastrocnemius motoneurons was not persistent, but instead gave way to depolarization after the first 30 ms. The net steady-state response after 0.5-1.0 s of stimulation was depolarization in all cells, regardless of motor unit type. This suggests that tonic sural input may be incapable of producing prolonged recruitment reversals.

Animals↗

Distribution of monosynaptic Ia excitatory post-synaptic potentials in the motor nucleus of the cat semitendinosus muscle.

Evidence is presented for a lack of localization of monosynaptic Ia excitatory post-synaptic potentials (e.p.s.p.s) in the motor nucleus supplying the atypical cat hind limb muscle semitendinosus, which has anatomically distinct in-series compartments. Recordings were made from dorsal root filaments containing functionally isolated Ia, spindle group II and Ib axons from the proximal and distal compartments of semitendinosus. Twitch of either of these in-series compartments resulted in accelerated discharge of Ia and spindle group II fibres in the other compartment. Ib fibres of either compartment showed an in-series response to twitch of a single compartment which was weaker than twitch of the whole muscle, a finding which was consistent with the diminished force produced by twitch of either compartment alone. In addition, intracellular recordings were made from semitendinosus motoneurones in anaesthetized low-spinal cats during electrical stimulation of the nerve branches to proximal semitendinosus and distal semitendinosus. Comparison of proximal semitendinosus and distal semitendinosus motoneurones failed to reveal any difference between the two cell groups with respect to the average Ia e.p.s.p. amplitude produced by either the proximal or distal semitendinosus nerve branch. However, e.p.s.p.s due to stimulation of distal semitendinosus were approximately 65% larger, on average, than those due to stimulation of proximal semitendinosus in either motoneurone group. Analysis of cell location along the rostro-caudal axis of the spinal cord indicated that the proximal and distal semitendinosus cell groups are largely co-extensive. Recordings of volleys in the proximal and distal semitendinosus nerve branches in response to stimulation of the L6, L7 and S1 dorsal roots showed that group I afferents from the proximal semitendinosus compartment tend to have a more rostral entry point to the spinal cord than do distal semitendinosus afferents. E.p.s.p. amplitude in either cell group due to stimulation of either nerve branch showed little dependence on cell location in the spinal cord. The results are discussed with respect to the relation between muscle function and the distribution of monosynaptic Ia connexions.

Action Potentials↗

Introduction to slow synaptic potentials and their neuromodulation by dopamine.

The existence of two muscarinically mediated slow postsynaptic potentials (PSPs) and a noncholinergic (peptidergic) late-slow PSP was established in the 1960s. These have synaptic delays and PSP durations 100-10,000 times those for the nicotinic (fast) excitatory post-synaptic potential (EPSP). Evidence is reviewed for an against the proposal that, in rabbit superior cervical ganglia, the slow (s-) inhibitory postsynaptic potential requires a second transmitter, dopamine, released by muscarinic action on interneurones (the small, intensely fluorescent cells). The s-EPSP in frog ganglia appears only in already depolarized cells by a muscarinic closure of the M (voltage-sensitive K+) channels. But the large s-EPSP in mammalian neurones, not depolarized, is generated largely via other mechanisms, especially one involving cyclic GMP. Dopamine also produces a long-term enhancement (LTE) of the muscarinic slow PSPs in rabbit superior cervical ganglia, whether dopamine is applied exogenously or released intraganglionically by preganglionic nerve impulses at 10 s-1. LTE is producible heterosynaptically, and it persists well over 3 h; a noncholinergic (peptide?) transmitter may contribute to the initial 30 min of LTE. LTE is mediated by a D1 receptor coupled to cyclic AMP; it is blocked by cyclic GMP or low Ca2+ or calmidazolium (a calmodulin inhibitor). The modulatory process of LTE has certain similarities to, but also fundamental differences from, the long-term potentiation known in the hippocampus.

Animals↗

Properties of single fibre excitatory post-synaptic potentials in triceps surae motoneurones.

1. E.p.s.p.s and terminal potentials (t.p.s) produced by the action of single medial gastrocnemius Ia afferent fibres were examined with intracellular microelectrodes in cat triceps surae motoneurones. 2. Simple terminal potentials (t.p.s) appeared as positive-negative diphasic waves with a single positive peak. Shape indices of excitatory post-synaptic potentials (e.p.s.p.s) recorded in conjunction with simple t.p.s indicate that these e.p.s.p.s were generated at an electrotonically confined compartment on the motoneurone somadendritic membrane. 3. Compound t.p.s. were similar ones, except that they had two or more positive peaks. Shape indices of e.p.s.p.s recorded in conjunction with compound t.p.s indicate that these e.p.s.p.s were generated at two or more electrotonically separate compartments. 4. E.p.s.p. latency and post-synaptic electrotonic delay were determined for a group of single fibre e.p.s.p.s with simple t.p.s. The shortest recorded latency was 0.26 msec. By subtracting estimated electrotonic delay, the shortest synaptic delay obtained for a medial gastrocnemius Ia single fibre e.p.s.p. was 0.17 msec. 5. The finding of a significant synaptic delay supports the hypothesis that the Ia-motoneurone synapse is a chemically mediated synapse.

Action Potentials↗