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PubMed1999

Chronic treatment with oestradiol does not alter in vitro LTP in subfield CA1 of the female rat hippocampus.

Population excitatory post-synaptic potentials (pEPSPs) were recorded in vitro from subfield CA1 of the hippocampus of female rats which had been ovariectomized and treated for 14 days with either oil or 17beta-oestradiol (10 microg/day). The currents applied to the Schaffer collateral-commissural input necessary to induce threshold, maximum and 50% maximum pEPSP responses did not differ between groups. Application of trains of pulses (0.1-1 s; 100 Hz) evoked post-tetanic and long-term (> 60 min) potentiation of pEPSP responses, the magnitude of which was related to stimulus duration in both groups. However, the degree of potentiation induced by near-threshold (0.1, 0.15 and 0.2 s) and saturating (1 s) stimuli did not differ between groups. Thus, despite reports that oestradiol can modulate synaptic spine density and glutamatergic and GABAergic components of the inputs to CA1, these data suggest that chronic oestradiol treatment has no effect on either the excitability or induction of LTP in the Schaffer collateral-commissural-CA1 pathway.

Animals↗

PubMed1986

Cortically and lingually induced postsynaptic potentials in trigeminal motoneurons after axotomy.

The membrane properties and the efficacy of excitatory and inhibitory synapses were studied in cat masseteric motoneurons (Mass Mns) after axotomy. In axotomized Mass Mns the slope of the primary range in the frequency-current relationship showed a higher gain than that of normal Mass Mns. The safety of antidromic invasion was increased and the initial segment component of antidromic action potentials could not be separated from the soma-dendritic component. In normal Mass Mns a single shock delivered to the orbital gyrus or the lingual nerve induced long-lasting inhibitory postsynaptic potentials (IPSPs). In two-thirds of Mass Mns explored 30 days after axotomy, a single shock delivered to the orbital gyrus or the lingual nerve evoked a mixture of inhibitory and excitatory synaptic potentials. In Mass Mns 50 days after axotomy, we have demonstrated that the major fraction of the total sample of explored Mass Mns showed long-lasting excitatory postsynaptic potentials followed by IPSPs. The results suggest that in Mass Mns, axotomy is followed by the decline of synaptic efficacy of inhibitory rather than of excitatory synapses.

Animals↗

PubMed2006

Stable competitive dynamics emerge from multispike interactions in a stochastic model of spike-timing-dependent plasticity.

In earlier work we presented a stochastic model of spike-timing-dependent plasticity (STDP) in which STDP emerges only at the level of temporal or spatial synaptic ensembles. We derived the two-spike interaction function from this model and showed that it exhibits an STDP-like form. Here, we extend this work by examining the general n-spike interaction functions that may be derived from the model. A comparison between the two-spike interaction function and the higher-order interaction functions reveals profound differences. In particular, we show that the two-spike interaction function cannot support stable, competitive synaptic plasticity, such as that seen during neuronal development, without including modifications designed specifically to stabilize its behavior. In contrast, we show that all the higher-order interaction functions exhibit a fixed-point structure consistent with the presence of competitive synaptic dynamics. This difference originates in the unification of our proposed "switch" mechanism for synaptic plasticity, coupling synaptic depression and synaptic potentiation processes together. While three or more spikes are required to probe this coupling, two spikes can never do so. We conclude that this coupling is critical to the presence of competitive dynamics and that multispike interactions are therefore vital to understanding synaptic competition.

Action Potentials↗

PubMed1995

Electrotonic coupling between two CA3 hippocampal pyramidal neurons: a distributed cable model with somatic gap-junction.

A model of a pair of electrotonically coupled CA3 hippocampal pyramidal neurons is presented. Each neuron is represented by a tapered equivalent cable attached to an isopotential soma. The synaptic potential in a neuron soma is determined as a consequence of electrical coupling to another soma that receives a synaptic input on its dendritic tree. Estimates of the coupling resistances, soma input resistances and soma-to-dendritic tree conductance ratio show that a substantial current may arise in a neuron as a consequence of synaptic activity in a neuron coupled to it. The small increase in decay time due to coupling in the model indicates that actual coupling is between more than just pairs of neurons.

Animals↗

PubMed1989

A biphasic excitability change in hindlimb motoneurons evoked by stimulation of the nucleus raphes magnus in the cat.

1. The influence of electrical stimulation of the nucleus raphes magnus (RM) on spinal segmental systems were examined. 2. RM stimulation produced an initial increase and a subsequent suppression of the amplitude of both fiextor and extensor lumbar monosynaptic reflex potentials (MSRs). 3. Intracellular recordings were made from alpha-motoneurons of the common peroneal nerve (flexor) and the tibial nerve (extensor). RM stimulation evoked postsynaptic potentials with a time course similar to that of MSR facilitation. 4. RM stimulation inhibited the aggregate excitatory synaptic potential (EPSP) evoked by stimulation of group I afferent fibers without apparent changes in the motoneuronal membrane potential. 5. These data suggest that the RM-evoked biphasic effect on MSR consists of early facilitation due to EPSP, and late inhibition possibly due to presynaptic inhibition of group I afferent fibers.

Animals↗

PubMed1993

The sensitivity of hippocampal long-term potentiation to nitric oxide synthase inhibitors is dependent upon the pattern of conditioning stimulation.

Inhibition of nitric oxide synthase prior to conditioning has been previously found to reduce levels of hippocampal long-term potentiation. In the present experiments in the rat, the reduction of long-term potentiation by nitric oxide synthase inhibitors was highly conditioning-dependent. We have characterized the relative importance of the number of conditioning stimulus trains, pulse number, intensity, and pattern in the reduction of long-term potentiation by nitric oxide synthase inhibitors. Long-term potentiation was reduced relative to control values only when multiple conditioning stimulus trains were presented at maximal stimulus intensity; potentiation produced by an equivalent number and intensity of stimuli presented in a single conditioning train was not reduced by nitric oxide synthase inhibitors, and multiple-train-induced potentiation was sensitive to nitric oxide synthase inhibitors only when maximal stimulation intensity was employed. Another form of synaptic potentiation, primed-burst potentiation, was reduced by nitric oxide synthase inhibition, while homosynaptic and heterosynaptic depression were unaffected. Our results support the hypothesis that conditioning-dependent release of nitric oxide can contribute to long-term potentiation, but also show that its blockade by nitric oxide synthase inhibitors is dependent on the nature of the conditioning stimulus, and that long-term potentiation can be generated that is apparently resistant to the effects of these drugs.

2-Amino-5-phosphonovalerate↗

PubMed1985

Perinatal glucocorticoids alter dentate gyrus electrophysiology.

Perinatal glucocorticoid administration produces permanent spatial discrimination learning deficits in rats, presumably referable to changes in the development of neural systems subserving such functions. Because the hippocampal dentate gyrus and its afferent/efferent circuitry appear selectively vulnerable to neonatal steroid treatments, we have examined adult rats treated with neonatally administered glucocorticoids using electrophysiological methods. The techniques were chosen to reveal the topographic and neurophysiologic responsiveness of the major afferent supply to the dentate gyrus. Rats of both sexes received either a high dose (100 mg/kg) or low dose (1 mg/kg) of the synthetic glucocorticoid dexamethasone on postnatal day four, with control subjects receiving an injection of saline. These dosages have been shown to disrupt hippocampal dependent learning [6,38]. Laminar depth profile analyses of entorhinal cortex-dentate gyrus afferents revealed a significant shift in the spatial distribution of evoked extracellular population synaptic potentials (EPSPs) in glucocorticoid treated subjects. Stimulus-response functions also differed between glucocorticoid treated and control subjects. While response amplitudes at threshold stimulus intensities did not differ between groups, at higher stimulus intensities population spike potentials and associated EPSPs differed in glucocorticoid versus control subjects.

Animals↗

PubMed1990

Cholinergically-induced changes in outward currents in hair cells isolated from the semicircular canal of the frog.

Two cholinergically-induced modulations of membrane conductances have been identified in hair cells isolated from the crista ampullaris of the leopard frog (Rana pipiens), using the whole cell recording configuration of the patch clamp technique. Of 56 crista hair cells tested, 28 showed drug-induced changes in membrane current or membrane potential which were repeatable and could be reversed with washout of drug. The predominant effect (observed in 20 hair cells) of acetylcholine (Ach, 100 microM) to 1mM) or carbachol (1 microM to 50 microM) applied to these hair cells was the reduction of an outward current corresponding to a change in conductance of approximately -0.22 nS. This action by Ach on hair cells has been inferred from previous studies of afferent fiber discharge which reported an increase in firing rate with stimulation of efferent fibers or exogenous application of cholinomimetics (Bernard et al., 1985; Valli et al., 1986; Guth et al., 1986; Norris et al., 1988a). The Ach-induced reduction in outward current was associated with a depolarization of the zero-current membrane potential by approximately +2.5 mV. In a total of 8 hair cells, an Ach-induced reversible increase in outward current was recorded. Changes in conductance were approximately +0.13 nS and were associated with a hyperpolarization of the zero-current membrane potential by approximately -2.2 mV. This current increase is likely to be responsible for the inhibitory post-synaptic potentials (IPSPs) which have previously been recorded intracellularly from acoustico-lateralis hair cells during stimulation of the efferent innervation (Flock and Russell, 1976; Ashmore and Russell, 1982; Art et al., 1984, 1985). Of the remaining 28 hair cells, six cells failed to exhibit any change in membrane conductance or membrane potential in the presence of cholinomimetics while an additional 15 cells exhibited decreases, and 7 cells exhibited increases in outward conductance, during application of Ach or carbachol, which were neither reversible with washout nor repeatable. The Ach-induced decrease in outward current could be reversible blocked by removal of Ca2+ from the external solution. The antagonism of the Ach-induced decrease in outward current by atropine (10(-5) M) suggests that this current may correspond to a facilitatory, 'atropine-preferring' Ach receptor mediated response previously identified in the isolated semicircular canal (Norris et al., 1988a).(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

PubMed2004

Ketamine blocks non-N-methyl-D-aspartate receptor channels attenuating glutamatergic transmission in the auditory cortex.

OBJECTIVE: To investigate the influence of ketamine on non-N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission in the auditory cortex. MATERIAL AND METHODS: Using whole-cell patch-clamp techniques on pyramidal neurons, we studied the effects of ketamine on excitatory post-synaptic potentials (EPSPs) evoked by electrical stimulation of internal capsule fibers in slices of gerbil auditory cortex. RESULTS: After blockade of the slow, NMDA receptor-mediated EPSP component with DL-2-amino-5-phosphonovaleric acid, application of ketamine in a concentration-dependent manner led to a reduction in the amplitude of fast, 6-cyano-7-nitroquinoxalinedione (CNQX)-sensitive EPSPs, accompanied by an increased membrane resistance. Blockade of non-NMDA glutamate receptors with CNQX prevented both effects. CONCLUSION: Ketamine reduces membrane conductance and glutamatergic excitation, in part by blocking alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor channels that may be constitutively active at a low level in slice preparations of auditory cortex.

Action Potentials↗

PubMed1971

Effects of lateral inhibition on fluctuations of the impulse rate.

Inhibition from neighboring eccentric cells has an effect on the variability of firing of a given eccentric cell. The reduction in the average impulse rate which is caused by inhibition decreases the variance of the impulse rate. However, this reduction of the average rate increases the coefficient of variation of the impulse rate. Inhibitory synaptic noise should add to the low frequency portion of the variance spectrum of the impulse rate. This occurs because of the slow time course of inhibitory synaptic potentials. As a consequence, inhibition decreases the signal-to-noise ratio for low frequency modulated stimuli.

Animals↗

PubMed1995

Zinc reduces dentate granule cell hyperexcitability in epileptic humans.

The hippocampi of epileptic patients with medial temporal lobe epilepsy exhibit a characteristic pattern of anatomical changes including cell loss and sprouting of the granule cell axons, the mossy fibers, into the inner molecular layer of the dentate. In addition to glutamate, mossy fibers release Zn2+. In the present study we investigated the action of Zn2+ on excitatory synaptic potentials in the dentate granule cells of patients with medial temporal lobe epilepsy. We show here that Zn2+ limits the duration of excitatory responses in these cells, probably by blocking the N-methyl-D-aspartate (NMDA) receptors. Zinc may, therefore, play an important role in limiting epileptiform activity in this issue.

2-Amino-5-phosphonovalerate↗

PubMed1974

Identification of cone mechanisms in graded responses of foveal striate cortex.

1. The earliest electrical response detectable in foveal striate cortex of anaesthetized Rhesus monkeys following light stimulation is a graded potential which is positive at the cortical surface and negative in the grey matter and has a peak latency of about 60 msec. The response is similar at both the on- and the off-phase of a light stimulus.2. The relationship of this graded potential to the depth of the recording electrode, to the latency of extracellular impulses and to post-synaptic potentials suggests that it is generated by the depolarization of cortical cells.3. Action spectra obtained in the presence of strong selective chromatic adaptation indicate the participation of all three cone mechanisms in this response.4. Each cone mechanism contributes a similar potential to the response but antagonism between cone mechanisms is apparent. The proportion in which a cone mechanism contributes to the response varies from one area to another implying topographical differences in the representation of cone mechanisms in striate cortex.

Adaptation, Ocular↗

PubMed1979

Electrotonic coupling among neuroendocrine cells in Aplysia.

1. We have discovered and characterized direct electrotonic synaptic coupling among a population of neuroendocrine (bag) cells in the parietovisceral ganglion of the marine gastropod Aplysia dactylomela. Pairs of ipsilateral and contralateral bag cells were impaled in vitro with microelectrodes. Current pulses applied through the electrometer amplifier to either cell influenced the other cell via electrotonic connections. 2. The coupling between bag cells was relatively weak when measured at the somata; the mean ratio of postsynaptic/presynaptic response amplitudes is 0.0075. Junctional rectification was not detected. The latency between pre- and postjunctional responses was long, up to 50 ms, a delay comparable to that for chemical synaptic transmission among neurons in this ganglion. Low-Ca2+/high-Mg2+ bathing solutions did not block transmission between bag cells, but did block chemical synaptic potentials in other identified neurons. 3. Postjunctional electrotonic responses had markedly slow time courses compared to the prejunctional responses, a characteristic that permitted summation of otherwise undetectable electrotonic PSPs and the demonstration of coupling between the two (bilateral) clusters of bag cells. 4. Based on extracellular recordings of their compound action potentials, the neurites of A. dactylomela bag cells extended a shorter distance (approximately 3 mm) along the connective than the neurites of A. californica or A. brasiliana. 5. Electrolytic lesions made along the neurites during intrasomatic coupling measurements significantly shortened the duration of postjuctional electrotonic responses, indicating that the neurites are widely electrically interconnected and, as a population, have a large effective membrane capacitance. The lesions furthermore revealed that an important site of electrotonic coupling is at the base of the pleurovisceral connective just rostral to the bag cell cluster. 6. The small-amplitude, long-latency and prolonged time course of postjunctional responses are interpreted to indicate remote and widespread coupling sites among the bag cells. This electrotonic coupling underlies the synchronized firing of the bag cells.

Action Potentials↗

PubMed1997

Changes of the inner time structures in the sequences of interspike intervals produced by the activity of excitatory and inhibitory synapses: simulation with Gaussian input processes.

The computer simulation of space-temporal summation of post-synaptic potentials of neurone's membrane demonstrated the outstanding changes in the inner time structures of generated interspike intervals. The output time series of ISIs were studied using non-standard kind of time analysis -- recurrence plot method. Using this technique we observed phenomenon of unification in inner time structures of output series. Further we identified such parameters of model which exerted the most considerable influence on this phenomenon.

Action Potentials↗

PubMed1979

Central generation of bursting in the feeding system of the snail, Lymnaea stagnalis.

The central generation of burst activity was investigated in the buccal ganglia of Lymnaea. Eight different patterns of burst activity were generated by one or two consecutive phases of compound synaptic potentials resulting from activity of neurones. These inputs acted upon the different endogenous properties of buccal neurones such as post-inhibitory rebound and spike adaptation. Effects of synaptic inputs were reinforced by by electrotonic coupling of some buccal neurones of the same type.

Action Potentials↗

PubMed1991

Refining the temporal definition of an association at the neuronal level using long-term potentiation and long-term depression in the dentate gyrus.

This study sharpens the temporal definition of an association in the context of long-term synaptic modification of the monosynaptic projections from entorhinal cortex to dentate gyrus in the anesthetized rat. The ipsilateral projection produces a powerful postsynaptic excitation and shows synaptic potentiation following 7.5 ms trains. On the other hand, brief, high-frequency contralateral stimulation just after this powerful postsynaptic excitation is followed by long-term depression (LTD) at the synapses of this pathway. Therefore, based on the differential induction of long-term potentiation (LTP) or LTD, a cell can distinguish associated pre- and postsynaptic activation at a temporal resolution at least as small as 7.5 ms.

Animals↗

PubMed1991

Adenosine depresses excitatory but not fast inhibitory synaptic transmission in area CA1 of the rat hippocampus.

The effects of adenosine on inhibitory synaptic transmission in area CA1 were examined using the rat hippocampal slice preparation and intracellular recording. Adenosine did not change fast inhibitory synaptic potentials (IPSPs) but depressed late IPSPs evoked by direct activation of interneurons in the presence of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV). Directly activated IPSPs were unchanged by the selective adenosine A1 receptor antagonist 8-cyclopentyltheophylline (CPT), but CPT reversed hyperpolarization and depression of late IPSPs produced by adenosine. These results indicate that adenosine depresses disynaptic IPSPs in area CA1 by decreasing synaptic activation of inhibitory neurons.

2-Amino-5-phosphonovalerate↗

PubMed2003

Contextual inhibitory gating of impulse traffic in the intra-amygdaloid network.

New data on the organization of the intra-amygdaloid circuit is reviewed, beginning with the basolateral (BL) complex, the main input station of the amygdala for sensory afferents, and concluding with the central (CE) nucleus, an important source of projections to brain-stem structures mediating fear responses. The BL complex is endowed with a highly divergent system of intrinsic glutamatergic connections. Yet, BL projection cells have unusually low firing rates. This apparent contradiction is explained by the presence of powerful inhibitory pressures in the BL amygdala: (1) interneurons that generate large-amplitude inhibitory synaptic potentials and (2) projection cells that express a Ca(2+)-dependent K(+) current that can be activated by subthreshold synaptic inputs. Likewise, excitatory projections from the BL amygdala to the CE nucleus are controlled by clusters of GABAergic neurons, termed the intercalated (ITC) cell masses. In response to BL inputs, ITC cells generate feedforward inhibition in CE neurons. However, ITC neurons exhibit properties that allow them to modify the amount of inhibition they generate depending on the distribution of BL activity in space and time. Indeed, ITC cell masses can inhibit each other via lateromedial connections. Moreover, they express an unusual K(+) conductance that modifies their response to BL inputs depending on their recent firing history. Thus, inhibitory mechanisms of the amygdala allow for flexible, context-dependent gating of BL impulses to the CE nucleus.

Amygdala↗