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PubMed1992

Epileptogenesis reduces the sensitivity of presynaptic gamma-aminobutyric acidB receptors on glutamatergic afferents in the amygdala.

Intracellular recordings were obtained from the basolateral amygdala in in vitro rat brain slice preparations to examine whether gamma-aminobutyric acid (GABA)B receptors are altered after in vivo kindling-induced epileptogenesis. Stimulating the stria terminalis evoked excitatory (EPSPs) and inhibitory (IPSPs) postsynaptic potentials in control neurons, and epileptiform bursting or enhanced EPSPs, but no IPSPs, in neurons from animals, 4 to 8 weeks after the last kindled seizure. Baclofen (0.1 nM-100 microM) depressed EPSPs in control and kindled basolateral amygdala neurons, but the EC50 appeared to be shifted 100-fold from 5 nM in control to 500 nM in kindled neurons. Further analysis suggested a high-affinity component may be affected in kind led neurons. The absence of IPSPs in kindled neurons could not account for this shift, because effects of baclofen on EPSP amplitude were reduced in kindled animals even when GABAA receptors were blocked with bicuculline methiodide (30 microM) and postsynpatic GABAB receptors with intracellular guanosine 5'-O-3-thiotriphosphate (10 mM); 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (10 microM) was also present to block bicuculline methiodide-induced bursting. Membrane responses to exogenously applied N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid were not affected by baclofen. Baclofen also hyperpolarized basolateral amygdala neurons and reduced membrane input resistance with an EC50 of 1 microM in control and kindled neurons. Post- but not presynaptic effects of baclofen were blocked by 2-hydroxy-saclofen (100 microM) and pertussis toxin pretreatment. In conclusion, kindling-induced epileptogenesis reduces the sensitivity of presynaptic GABAB receptors, an effect which may contribute to the enhancement of excitatory transmission in kindled animals. Furthermore, different pharmacological properties of pre- and postsynaptic receptors in the amygdala suggest two distinct populations of GABAB receptors whose long-lasting responses to kindling-induced seizures are different.

Animals↗

PubMed1997

Neurosteroid prolongs GABAA channel deactivation by altering kinetics of desensitized states.

Fast applications of GABA (1 mM) to nucleated and outside-out patches excised from granule neurons in cerebellar slices from developing rats evoked currents with a double exponential time course reminiscent of that of IPSCs. A neurosteroid 3alpha, 21dihydroxy-5alpha-pregnan-20-one (THDOC) remarkably increased the slow deactivation time constant and slowed down recovery from desensitization, as estimated by paired-pulse GABA applications. THDOC also reduced the amplitude of GABA currents, whereas it failed to affect the fast deactivation component and its relative contribution to peak amplitude. The effects of THDOC on slow deactivation were greater in rats younger than postnatal day 13 (P13) as compared with rats at P30-P35. THDOC failed to alter deactivation of short responses induced by a less-potent agonist taurine at saturating doses. These responses had deactivation kinetics described by a fast single exponential decay, little desensitization, and quick recovery. However, THDOC slowed deactivation if taurine responses were long enough to allow consistent desensitization, suggesting that desensitized states are required for the neurosteroid to modulate GABA responses. In outside-out patches, just as desensitized states prolonged GABA responses by producing reopening of channels activated by brief GABA pulses, THDOC increased the channel open probability by further increasing the number of late channel openings, resulting in a prolongation of the slow deactivation. Our data suggest that neurosteroid potentiates the inhibitory postsynaptic transmission via the prolongation of the slow deactivation and that the alteration of kinetics of entry and exit from desensitized states underlies the allosteric modification of GABAA receptors by neurosteroids.

Age Factors↗

PubMed2006

Cortical network modeling: analytical methods for firing rates and some properties of networks of LIF neurons.

The circuitry of cortical networks involves interacting populations of excitatory (E) and inhibitory (I) neurons whose relationships are now known to a large extent. Inputs to E- and I-cells may have their origins in remote or local cortical areas. We consider a rudimentary model involving E- and I-cells. One of our goals is to test an analytic approach to finding firing rates in neural networks without using a diffusion approximation and to this end we consider in detail networks of excitatory neurons with leaky integrate-and-fire (LIF) dynamics. A simple measure of synchronization, denoted by S(q), where q is between 0 and 100 is introduced. Fully connected E-networks have a large tendency to become dominated by synchronously firing groups of cells, except when inputs are relatively weak. We observed random or asynchronous firing in such networks with diverse sets of parameter values. When such firing patterns were found, the analytical approach was often able to accurately predict average neuronal firing rates. We also considered several properties of E-E networks, distinguishing several kinds of firing pattern. Included were those with silences before or after periods of intense activity or with periodic synchronization. We investigated the occurrence of synchronized firing with respect to changes in the internal excitatory postsynaptic potential (EPSP) magnitude in a network of 100 neurons with fixed values of the remaining parameters. When the internal EPSP size was less than a certain value, synchronization was absent. The amount of synchronization then increased slowly as the EPSP amplitude increased until at a particular EPSP size the amount of synchronization abruptly increased, with S(5) attaining the maximum value of 100%. We also found network frequency transfer characteristics for various network sizes and found a linear dependence of firing frequency over wide ranges of the external afferent frequency, with non-linear effects at lower input frequencies. The theory may also be applied to sparsely connected networks, whose firing behaviour was found to change abruptly as the probability of a connection passed through a critical value. The analytical method was also found to be useful for a feed-forward excitatory network and a network of excitatory and inhibitory neurons.

Action Potentials↗

PubMed1977

The mechanism of action of diphenylhydantoin on invertebrate neurons. II. Effects on synaptic mechanisms.

The effect of diphenylhydantoin (DPH) on certain synapses of neurons in the abdominal ganglion of Aplysia and on the gamma-aminobutyric acid (GABA) mediated inhibitory synapse of the crayfish stretch receptor neuron (SRN) has been studied. DPH decreases the amplitude of the excitatory postsynaptic potential, but is ineffective on the "short" ACh mediated, Cl- dependent, inhibitory postsynaptic potential (IPSP) in Aplysia. However, it facilitates the "long" ACh mediated, K+ dependent, IPSP, in this same group of neurons. DHP has a profound effect on the GABA mediated, Cl- dependent, inhibitory synapse of the SRN. The time course of the IPSP is prolonged up to 10 times control values, due to an increased and prolonged postsynaptic conductance. Similar results have been obtained in the SRN with iontophoretic application of GABA. This selective effect of DPH on synaptic mechanisms, especially in view of the role of GABA and ACh as putative transmitters in the mammalian nervous system, may play an important role for the anticonvulsant action of DPH.

Acetylcholine↗

PubMed2006

Synaptic origin of the respiratory-modulated activity of laryngeal motoneurons.

To determine the synaptic source of the respiratory-related activity of laryngeal motoneurons, spike-triggered averaging of the membrane potentials of laryngeal motoneurons was conducted using spikes of respiratory neurons located between the Bötzinger complex and the rostral ventral respiratory group as triggers in decerebrate, paralyzed cats. We identified one excitatory and two inhibitory sources for inspiratory laryngeal motoneurons, and two inhibitory sources for expiratory laryngeal motoneurons. In inspiratory laryngeal motoneurons, monosynaptic excitatory postsynaptic potentials were evoked by spikes of inspiratory neurons with augmenting firing patterns, and monosynaptic inhibitory postsynaptic potentials (IPSPs) were evoked by spikes of expiratory neurons with decrementing firing patterns and by spikes of inspiratory neurons with decrementing firing patterns. In expiratory laryngeal motoneurons, monosynaptic IPSPs were evoked by spikes of inspiratory neurons with decrementing firing patterns and by spikes of expiratory neurons with augmenting firing patterns. We conclude that various synaptic inputs from respiratory neurons contribute to shaping the respiratory-related trajectory of membrane potential of laryngeal motoneurons.

Action Potentials↗

PubMed1985

Electrophysiological studies on the postnatal development of intracerebellar nuclei neurons in rat cerebellar slices maintained in vitro. I. Postsynaptic potentials.

The development of the synaptic responses of intracerebellar nuclei neurons was studied in the rat by the use of thick sagittal cerebellar slices maintained in vitro. It has been shown that functional excitatory synapses are present on these neurons from birth, probably due to climbing and/or mossy fiber collaterals; functional inhibitory synapses, due to monosynaptic projections of Purkinje cell axons onto intracerebellar nuclei, are present as early as postnatal day 2; and a more complex pattern of synaptic responses, including short latency excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs), longer latency IPSPs, and late depolarizing responses, can be elicited in nuclear neurons as early as postnatal day 3, indicating an early development of some complete functional cerebellar circuits involving the intracerebellar nuclei.

Animals↗

PubMed1997

Potentiation of glutamatergic EPSPs in rat CA1 hippocampal neurons after selective cholinergic denervation by 192 IgG-saporin.

A complete and selective destruction of the basal forebrain cholinergic neurons projecting to the cerebral cortex and the hippocampus was induced in the rat by the toxin 192 IgG-saporin. Using electrophysiologic techniques, we have investigated the consequences of this cholinergic denervation on inhibitory and excitatory synaptic responses of CA1 pyramidal cells in rat hippocampal slices ex vivo. Histochemical experiments were performed in slices from control and 192 IgG-saporin-treated rats to check the efficacy of the intracerebroventricular injection of the immunotoxin. Stimulation of stratum radiatum elicits a glutamatergic excitatory postsynaptic potentials followed by a biphasic GABAergic inhibitory postsynaptic potential (IPSP). No significant change in IPSP was observed in 192 IgG-saporin-treated rats. By contrast, the N-methyl-D-aspartate (NMDA) and to a lesser extent the non-NMDA components of the glutamatergic response were potentiated in these animals. The possible pre- and postsynaptic mechanisms of this potentiation were discussed.

Animals↗

PubMed2002

Inhibitory component of the resistance reflex in the locomotor network of the crayfish.

The aim of this study was to investigate the inhibitory components of a resistance reflex in the walking system of the crayfish. This study was performed using an in vitro preparation of several thoracic ganglia including motor nerves and the proprioceptor that codes movements of the second joint (coxo-basipodite chordotonal organ-CBCO). Sinusoidal movements were imposed on the CBCO, and intracellular responses were recorded from levator (Lev) and depressor (Dep) motoneurons (MNs). We found that in MNs that oppose the imposed movements (e.g., the Lev MNs during the imposed downward movement), the response consists in a depolarization resulting from the summation of excitatory postsynaptic potentials (EPSPs). A movement in the opposite direction resulted in hyperpolarization during which inhibitory postsynaptic potentials (IPSPs) summated. The inhibitory pathway to each MN is oligosynaptic (i.e., composed of a small number of neurons in series) and involves spiking interneurons because it was blocked in the presence of a high-divalent cation solution. The IPSPs were mediated by a chloride conductance because their amplitude was sensitive to the chloride concentration of the bathing solution and because they were blocked by the chloride channel blocker, picrotoxin. Resistance reflex IPSPs related to single CBCO neurons could be identified. These unitary IPSPs were blocked in the presence of 3-mercapto-propionic acid, an inhibitor of gamma-amino-butyric acid (GABA) synthesis, indicating that they are mediated by GABA. In addition to this GABAergic pathway, electrical stimulation of the CBCO sensory nerve induced compound IPSPs that were blocked by glutamate pyruvate transaminase (GPT), indicating the presence of glutamatergic inhibitory pathways. These glutamatergic interneurons do not appear to be involved in the resistance reflex, however, as GPT did not block the unitary IPSPs. Functionally, the resistance reflex is mainly supported by movement-coding CBCO sensory neurons. We demonstrate that such movement-coding CBCO neurons produce both monosynaptic EPSPs in the MNs opposing imposed movements and oligosynaptic IPSPs in the antagonistic motoneurons. These results highlight the similarities between the inhibitory pathways in resistance reflex of the crayfish and in the stretch reflex of vertebrates mediated by Ia inhibitory interneurons.

Animals↗

PubMed1994

Properties of isolated GABAB-mediated inhibitory postsynaptic currents in hippocampal pyramidal cells.

Whole-cell recording techniques were used to record isolated slow inhibitory postsynaptic currents in CA1 pyramidal neurons from rat hippocampal slices. Application of 6-cyano-7-nitroquinoxaline-2,3-dione and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid eliminated excitatory synaptic transmission, resulting in a 38% reduction in slow inhibitory postsynaptic current magnitude. Subsequent addition of the GABAA antagonist picrotoxin caused a further decrease in slow inhibitory postsynaptic current amplitude. The remaining, isolated slow inhibitory postsynaptic current was blocked by the GABAB antagonist 2-hydroxysaclofen and when cesium was substituted for intracellular potassium. The kinetics of isolated slow inhibitory postsynaptic currents were characterized by single exponential, fourth power activation, and double exponential inactivation. These slow inhibitory postsynaptic currents had a reversal potential of -85.7 +/- 1.6 mV, and a slope conductance of 935 +/- 277 pS. Single slow inhibitory postsynaptic currents carried a total charge flux of 13.4 +/- 7.6 pC. Repetitive stimulation up to 1 Hz progressively reduced steady-state slow inhibitory postsynaptic current amplitude. This attenuation was characterized by a decrease in slope conductance, but slow inhibitory postsynaptic current reversal potential remained unchanged, as did slow inhibitory postsynaptic current kinetics. These results indicate that, under physiological conditions, both ionotropic glutamate- and GABAA-mediated transmission contribute to slow inhibitory postsynaptic current recruitment. Given this finding, activity-dependent decreases in GABAA transmission could contribute to slow inhibitory postsynaptic current depression, though not exclusively, since isolated slow inhibitory postsynaptic currents also demonstrated this property. The use-dependent depression of isolated slow inhibitory postsynaptic currents may be a consequence of a reduction in transmitter release.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1997

Similar inhibitory processes dominate the responses of cat lateral amygdaloid projection neurons to their various afferents.

To investigate the impact of inhibitory processes on responses of lateral amygdaloid (LAT) neurons, intracellular recordings were obtained from identified LAT projection neurons in barbiturate-anesthetized cats. Synaptic responses evoked by perirhinal (PRH), entorhinal (ENT), basomedial, and LAT stimulation were investigated. Regardless of stimulation site, responses consisted of an excitatory postsynaptic potential (EPSP) that either preceded and was truncated by an inhibitory postsynaptic potential (IPSP) or occurred just after the IPSP onset. IPSPs were monophasic, lasted hundreds of milliseconds, and were of such large amplitude and rapid onset that they effectively opposed the EPSPs, generally preventing orthodromic spikes. All sites elicited IPSPs with relatively negative reversal potentials around -85 mV. Experiments analyzing the underlying ionic mechanisms are presented in the companion paper. Evoked responses were similar to synaptic potentials associated with spontaneous EEG events, known as simple (small, monophasic) and complex (large, triphasic) ENT sharp potentials (SPs), with no difference between the reversals of evoked and SP-related IPSPs (-83.2 +/- 2.7 mV). IPSPs coinciding with complex SPs truncated SP-related EPSPs more rapidly and had larger amplitudes and longer durations than those related to simple SPs. These differences reflected the fact that the amplitude and duration of SP-related IPSPs were correlated with SP amplitude. Similar variations were reproduced in evoked IPSPs by varying the stimulus intensity. Low intensities generated predominantly excitatory responses consisting of EPSPs sometimes followed by small IPSPs, whereas high intensities evoked predominantly inhibitory responses comprised of a large IPSP that truncated or occluded the EPSPs. Orthodromic spikes were elicited only in a narrow range of intermediate intensities. These changes in the evoked response primarily reflected increases in the IPSP evoked at high intensities. PRH stimulation at different rostro-caudal levels demonstrated that rostral sites elicited larger EPSPs and IPSPs with shorter latencies and longer durations than caudal sites. These differences probably reflect contrasting patterns of activity spread through the PRH cortex, suggesting that the intact cortical circuitry allowed a temporally distributed activation of inhibitory interneurons and thereby partly explains the long duration and monophasic nature of the IPSPs. Inhibition, thus, plays a primary role in shaping LAT neuronal responses. The profuse intrinsic connectivity of the LAT nucleus and parahippocampal cortices may underlie the relatively invariant response pattern of LAT neurons and suggests a common mode of information processing, based upon quantitative, rather than qualitative, differences in activation of LAT circuitry. Therefore we propose that effective transmission of signals through the LAT nucleus may require activation of specifically sized neuronal ensembles, rather than widespread afferent excitation.

Afferent Pathways↗

PubMed1995

Properties of unitary IPSPs evoked by anatomically identified basket cells in the rat hippocampus.

Hippocampal pyramidal cells receive GABA-mediated synaptic input from several distinct interneurons. In order to define the effect of perisomatic synapses, intracellular recordings were made with biocytin-containing microelectrodes from synaptically connected inhibitory and pyramidal cell pairs in subfields CA1 and CA3 of the rat hippocampus. Subsequent physiological analysis were restricted to the category of cells, here referred to as basket cells (n = 14), which had an efferent synaptic target profile (n = 282 synaptic contacts) of predominantly somatic (48.2%) and proximal dendritic synapses (45.0%). Electron microscopic analysis revealed that in two instances identified postsynaptic pyramidal cells received a total of 10 and 12 labelled basket cell synapses respectively. At an average membrane potential of -57.8 +/- 4.6 mV, unitary inhibitory postsynaptic potentials (IPSPs; n = 24) had a mean amplitude of 450 +/- 238 microV, a 10-90% rise time of 4.6 +/- 3.2 ms and, measured at half-amplitude, a mean duration of 31.6 +/- 18.2 ms. In most instances (n = 19) the IPSP decay could be fitted with a single exponential with a mean time constant of 32.4 +/- 18.0 ms. Unitary basket cell-evoked IPSPs (n = 5) was extrapolated to be at -74.9 +/- 6.0 mV. Averages of unitary IPSPs had a mean calculated conductance of 0.95 +/- 0.29 nS, ranging from 0.52 to 1.16 nS. Unitary basket cell IPSPs (n = 3) increased in amplitude by 26.6 +/- 19.9% following bath application of the GABAB receptor antagonist CGP 55845A [correction of CGP 35845A] (1-4 microM), whereas subsequent addition of the GABAA receptor antagonist bicuculline (10-13 microM) reduced the IPSP amplitude to 13.5 +/- 3.1% of the control response. Rapid presynaptic trains of basket cell action potentials resulted in the summation of up to four postsynaptic responses (n = 5). However, any increase in the rate of tonic firing (2- to 10-fold) led to a > 50% reduction of the postsynaptic response amplitude. At depolarized membrane potentials, averaged IPSPs could be followed by a distinct depolarizing overshoot or postinhibitory facilitation (n = 4). At firing threshold, pyramidal cells fired postinhibitory rebound-like action potentials, the latter in close temporal overlap with the depolarizing overshoot. In conclusion, hippocampal basket cells have been identified as one source of fast, GABAA receptor-evoked perisomatic inhibition. Unitary events are mediated by multiple synaptic release sites, thus providing an effective mechanism to avoid total transmission failures.

Action Potentials↗

PubMed2006

Monitoring synaptic transmission in primary neuronal cultures using local extracellular stimulation.

Various techniques have been applied for the functional analysis of synaptic transmission in cultured neurons. Here, we describe a method of studying synaptic transmission in neurons cultured at high-density from different brain regions such as the cortex, striatum and spinal cord. We use postsynaptic whole-cell recordings to monitor synaptic currents triggered by presynaptic action potentials that are induced by brief stimulations with a nearby extracellular bipolar electrode. Pharmacologically isolated excitatory or inhibitory postsynaptic currents can be reliably induced, with amplitudes, synaptic charge transfers, and short-term plasticity properties that are reproducible from culture to culture. We show that the size and kinetics of pharmacologically isolated inhibitory postsynaptic currents triggered by single action potentials or stimulus trains depend on the Ca2+ concentration, temperature and stimulation frequency. This method can be applied to study synaptic transmission in wildtype neurons infected with lentiviruses encoding various components of presynaptic release machinery, or in neurons from genetically modified mice, for example neurons carrying floxed genes in which gene expression can be acutely ablated by expression of Cre recombinase. The preparation described in this paper should be useful for analysis of synaptic transmission in inter-neuronal synapses formed by different types of neurons.

Animals↗

PubMed1979

Depolarization of neurones in the isolated olfactory cortex of the guinea-pig by gamma-aminobutyric acid.

1 Effects of gamma-aminobutyric acid (GABA) on single neurones in slices of guinea-pig olfactory cortex maintained in vitro were recorded with single intracellular microelectrodes. The average resting potential of 52 cells was -75 mV and apparent input resistance ranged from 20 to 200 MOmega.2 Superfusions of GABA over the slice invariably depolarized the neurones and reduced their input resistance. The minimum effective concentration was 50 to 200 muM.3 The reversal potential for the depolarization produced by 0.1 mM GABA (E(g)) was -66 +/- 2 mV. At concentrations >0.1 mM the reversal potential became progressively more positive (-55 to -50 mV).4 Reduction of external chloride, with isethionate as the substitute anion, increased the amplitude of the depolarization.5 GABA reduced the amplitude of the excitatory postsynaptic potential produced by lateral olfactory tract stimulation, and occluded or reversed the subsequent depolarizing recurrent inhibitory postsynaptic potential.6 Action potentials elicited by injection of depolarizing current or by focal antidromic stimulation were slowed and reduced in amplitude by GABA.7 The effects of GABA on membrane conductance (potency = 1) were duplicated by 3-aminopropanesulphonic acid (potency = 20), beta-alanine (0.5), beta-amino-n-butyric acid (0.5), glycine (0.3) and L-2,4-diaminobutyric acid (0.2). For a given conductance change, 3-aminopropanesulphonic acid, glycine and beta-alanine produced less depolarization than did GABA.8 It is concluded that the action of GABA on the neurones is compatible with a role in mediating recurrent postsynaptic inhibition.

Action Potentials↗

PubMed1993

On the sites of presynaptic inhibition by neuropeptide Y in rat hippocampus in vitro.

Neuropeptide Y (NPY) reduces excitatory synaptic transmission between stratum radiatum and CA1 pyramidal cells in rat hippocampal slice in vitro by a presynaptic action. To understand NPY's role in the control of excitability in hippocampus, its actions on excitatory and inhibitory synaptic transmission were examined, using intracellular, sharp microelectrode, and tight-seal, whole cell recordings from principal neurons in areas CA1, CA3, and dentate. Bath application of 1 microM NPY reversibly inhibited excitatory postsynaptic potentials (EPSPs) evoked in CA1 pyramidal cells from either stratum radiatum or stratum oriens by about 50%. Neuropeptide Y also inhibited EPSPs at mossy fiber-CA3, stratum oriens-CA3, and CA3-CA3 synapses by between 45% and 55%. As in CA1, the action of NPY was presynaptic. By contrast, NPY did not inhibit EPSPs evoked in dentate granule cells from either perforant path or commissural inputs. Neuropeptide Y did not alter postsynaptic membrane properties in any cell type. Although NPY attenuated the orthodromically evoked (stratum radiatum) inhibitory postsynaptic potentials in CA1 pyramidal cells by about the same amount as it inhibited the EPSPs, it did not affect the IPSPs evoked in the same cells by antidromic stimulation from alveus. Inhibitory postsynaptic potentials evoked in pharmacological isolation in CA1, CA3, or dentate were also not significantly affected by NPY. The evidence supports the hypothesis that NPY acts at feedforward excitatory synapses to presynaptically reduce the amplitude of excitation as it travels through hippocampal circuits. By contrast, synaptically mediated inhibition is not directly affected by NPY.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed2006

Differential effect of supraspinal modulation on the nociceptive withdrawal reflex and pain sensation.

OBJECTIVE: To study whether the nociceptive withdrawal reflex (WR) and pain sensation are differentially affected by supraspinal modulation and to determine the nature of this modulation. METHODS: The WR and pain sensation elicited by electrical stimulation were measured in complete spinal cord injury (SCI) subjects and in intact controls under two different experimental conditions; "facilitation" and "neutral" control. RESULTS: Pain sensation was the same under both conditions, whereas the characteristics of the WR were highly dependent on them. In intact body regions the WR threshold was similar to pain threshold under facilitation but was near pain tolerance in neutral conditions. Furthermore, WR was elicited in 100% of trials under facilitation but only in 57% of trials in neutral conditions. Thresholds of WR in paralyzed regions were significantly higher than in intact regions (p<0.001). The former showed a clear stimulus-response relationship as did pain sensation whereas the WR in intact regions did not. CONCLUSIONS: The WR and pain sensation are differentially affected by supraspinal modulation. The WR is subject to both excitatory and inhibitory influences, depending on the instructions subjects receive. SIGNIFICANCE: The experimental setup and subjects' mental state should be considered when interpreting changes in the WR. Extreme caution should be employed when utilizing reflexive indices as a measure of pain. Verbal report seems a more suitable tool to evaluate pain since it is relatively stable with repeated measurements and in accordance with stimulation intensity.

Adult↗

PubMed2002

Effects of paired-pulse and repetitive stimulation on neurons in the rat medial geniculate body.

Many behaviorally relevant sounds, including language, are composed of brief, rapid, repetitive acoustic features. Recent studies suggest that abnormalities in producing and understanding spoken language are correlated with abnormal neural responsiveness to such auditory stimuli at higher auditory levels [Tallal et al., Science 271 (1996) 81-84; Wright et al., Nature 387 (1997) 176-178; Nagarajan et al., Proc. Natl. Acad. Sci. USA 96 (1999) 6483-6488] and with abnormal anatomical features in the auditory thalamus [Galaburda et al., Proc. Natl. Acad. Sci. USA 91 (1994) 8010-8013]. To begin to understand potential mechanisms for normal and abnormal transfer of sensory information to the cortex, we recorded the intracellular responses of medial geniculate body thalamocortical neurons in a rat brain slice preparation. Inferior colliculus or corticothalamic axons were excited by pairs or trains of electrical stimuli. Neurons receiving only excitatory collicular input had tufted dendritic morphology and displayed strong paired-pulse depression of their large, short-latency excitatory postsynaptic potentials. In contrast, geniculate neurons receiving excitatory and inhibitory collicular inputs could have stellate or tufted morphology and displayed much weaker depression or even paired-pulse facilitation of their smaller, longer-latency excitatory postsynaptic potentials. Depression was not blocked by ionotropic glutamate, GABA(A) or GABA(B) receptor antagonists. Facilitation was unaffected by GABA(A) receptor antagonists but was diminished by N-methyl-D-aspartate (NMDA) receptor blockade. Similar stimulation of the corticothalamic input always elicited paired-pulse facilitation. The NMDA-independent facilitation of the second cortical excitatory postsynaptic potential lasted longer and was more pronounced than that seen for the excitatory collicular inputs. Paired-pulse stimulation of isolated collicular inhibitory postsynaptic potentials generated little change in the second GABA(A) potential amplitude measured from the resting potential, but the GABA(B) amplitude was sensitive to the interstimulus interval. Train stimuli applied to collicular or cortical inputs generated intra-train responses that were often predicted by their paired-pulse behavior. Long-lasting responses following train stimulation of the collicular inputs were uncommon. In contrast, corticothalamic inputs often generated long-lasting depolarizing responses that were dependent on activation of a metabotropic glutamate receptor. Our results demonstrate that during repetitive afferent firing there are input-specific mechanisms controlling synaptic strength and membrane potential over short and long time scales. Furthermore, they suggest that there may be two classes of excitatory collicular input to medial geniculate neurons and a single class of small-terminal corticothalamic inputs, each of which has distinct features.

Animals↗

PubMedDate not supplied

[Effect of inhibitory-inhibitory connections and the form of postsynaptic potentials on the formation of rhythmic processes in the cerebral cortex: analysis of the approximate equation of the electroencephalogram].

The integral equation, describing the electroencephalogram and taking into account the steepness of PSP fronts, delays of action potential spread, and neural Inhibito-inhibitory connections, is derived and analysed. The damping decrements and frequencies of the equation solutions in the continuum of parameters, associated with total numbers excitatory and inhibitory neurons in the cerebral cortex, density of synapses, and average level of excitation of cortical neurons are considered. The steepness of PSP fronts does not qualitatively change the solution's structure with the influences of EPSP and IPSP fronts being opposite. The inhibito-inhibitory connections expand the damped solutions regions. The delays of action potential spread between excitatory neurons enlarge the damped solutions region, and the delays in ones between inhibitory and excitatory neurons decrease it, especially for higher frequencies.

Cerebral Cortex↗

PubMed1998

Interaction of GABAB-mediated inhibition with voltage-gated currents of pyramidal cells: computational mechanism of a sensory searchlight.

Interaction of GABAB-mediated inhibition with voltage-gated currents of pyramidal cells: computational mechanism of a sensory searchlight. J. Neurophysiol. 80: 3197-3213, 1998. This study examines, in the in vitro electrosensory lateral line lobe (ELL) slice preparation, mono- and disynaptic inhibition in pyramidal cells evoked by stimulation of the direct descending pathway from nucleus praeminentialis (Pd). The pathway forms the stratum fibrosum (StF) in the ELL and consists of excitatory fibers from Pd stellate cells that make monosynaptic contact with pyramidal cells and disynaptic inhibitory contacts via local interneurons and of GABAergic inhibitory fibers from Pd bipolar cells. Single or tetanic stimulation (physiological rates of 100-200 Hz) of the StF produced excitatory postsynaptic potentials (EPSPs) or compound EPSPs in ELL pyramidal cells. Slow (>600 ms) and fast inhibitory postsynaptic potentials (IPSPs; 5-50 ms) also were evoked. Application of gamma-aminobutyric acid-A (GABAA) antagonists blocked the fast inhibition and dramatically increased the firing rate response to StF tetanic stimuli. GABAA antagonists also increased the amplitude of the slow IPSP. The slow IPSP was reduced by GABAB antagonists. Blockade of excitatory amino acid (EAA) synaptic transmission allowed the monosynaptic bipolar-cell-mediated inhibition to be studied in isolation: EAA antagonists blocked most of the EPSP response to StF stimulation leaving fast and (an increased amplitude) slow IPSP components. The bipolar-cell IPSPs were mediated by GABAA and GABAB receptors as they were sensitive to GABAA and GABAB antagonists. The bipolar-cell IPSPs scaled with stimulation rate (20-400 Hz), reaching a maximum amplitude at 200 Hz. Inhibitory efficacy of bipolar-cell slow IPSPs were tested by their ability to reduce spiking in the face of sustained or brief current pulses. Established spike trains (by sustained injected current) were little affected by the onset of the slow IPSP. Weak brief currents injected during the slow IPSP were strongly inhibited. Strong brief currents could overcome the slow IPSP inhibitory effect. Inhibition was observed to interact with the intrinsic IA-like K+ currents to produce a complex control of cell spiking. Hyperpolarizing inhibition removes inactivation of IA to prevent subsequent inputs from driving the cell to threshold. Established depolarizing inputs, having allowed IA to inactivate, enable the cell to be highly sensitive to further depolarizing input. The term "conditional inhibition" is proposed to describe the general phenomenon where synaptic inhibition interacts with voltage-sensitive intrinsic currents.

Animals↗