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J J Jack

Publications and source records attributed to J J Jack.

At least 19 recordsLinked to original sources
PubMed2001

Evidence that glutamate acting on presynaptic type-II metabotropic glutamate receptors alone does not fully account for the phenomenon of depolarisation-induced suppression of inhibition in cerebellar Purkinje cells.

Depolarisation-induced suppression of inhibition (DSI) is a form of short-term synaptic plasticity at gamma-aminobutyric-acid-(GABA)ergic synapses between principal neurons and interneurons in both the cerebellum and the hippocampus. The induction of DSI involves an intracellular calcium-dependent release of a retrograde messenger from the postsynaptic principal neuron (Purkinje cell/pyramidal cell in cerebellum/hippocampus) onto presynaptic interneurons, where it is thought to bind to guanine nucleotide-binding protein (G protein)-coupled receptors and subsequently reducing GABA release from these interneurons onto the postsynaptic principal neuron. Pharmacological studies have indicated that glutamate might be a retrograde messenger in both cerebellum and hippocampus, where, in the former at least, it seems to activate type-II metabotropic glutamate receptors (mGluRs). Using LY-341495, a recently described, highly specific and potent antagonist of type-II mGluRs, to block these receptors reduced DSI slightly, but significantly, in spite of the fact that this antagonist completely suppressed the effects of stimulating type-II mGluRs with a specific agonist. Activation of type II mGluRs alone thus cannot account fully for DSI in cerebellum and hence other mechanisms are involved in its induction. Such mechanisms probably involve an additional retrograde signal.

Amino Acids↗
PubMed1999

Intracortical excitation of spiny neurons in layer 4 of cat striate cortex in vitro.

Recordings were made from pairs of neurons in cat striate visual cortex in vitro to study the AMPA-channel-mediated components of intracortical excitatory synaptic connections between layer 4 spiny neurons and between layer 6 and layer 4 spiny neurons. Forty-six of the 72 cells recorded were identified morphologically. They consisted of spiny stellate and pyramidal cells in layer 4, and pyramidal cells in layer 6. Connections between layer 4 excitatory cells involve excitatory postsynaptic potentials (EPSPs) averaging 949 microV, with an average coefficient of variation of 0.21 (n = 30). The synapses operate at very high release probabilities (0.69-0.98). With repetitive stimulation these EPSPs show varying degrees of depression, largely mediated by presynaptic changes in release probability. Four pairs of layer 4 cells were reciprocally connected. The connections from layer 6 to layer 4 involve smaller, more variable EPSPs, with an average amplitude of 214 microV, and average coefficient of variation 0.72 (n = 7). These synapses operate at moderately high release probabilities (0.37-0.56). They show facilitation with repetitive stimulation, mediated largely by presynaptic changes in release probability. One excitatory connection from a layer 4 neuron to a layer 6 pyramidal cell was also detected. Thus, layer 4 spiny neurons receive effective excitation from two intracortical sources that have different synaptic dynamics and are likely to contribute significantly to the temporal properties of these cells in vivo.

Animals↗
PubMed1998

Synaptic interactions between smooth and spiny neurones in layer 4 of cat visual cortex in vitro.

1. Dual intracellular recording was used to examine the interactions between neighbouring spiny (excitatory) and smooth (inhibitory) neurones in layer 4 of cat visual cortex in vitro. Synaptic connections were found in seventeen excitatory-inhibitory neurone pairs, along with one inhibitory-inhibitory connection. 2. Fast excitatory inputs onto smooth neurones (basket cells) from spiny cells (spiny stellate or pyramidal cells) (n = 6) produce large excitatory postsynaptic potentials (EPSPs) of up to 4 mV mean amplitude, whereas basket cells evoke slower inhibitory postsynaptic potentials (IPSPs) in their postsynaptic targets (n = 17), of smaller amplitude (up to 1.6 mV at membrane potentials of -60 mV). 3. Both types of PSP appear to be multiquantal, and both may exhibit depression of up to 60 % during short trains of presynaptic spikes. This depression can involve presynaptic and/or postsynaptic factors. 4. One-third (n = 5) of the spiny cell-smooth cell pairs tested were reciprocally connected, and in the one pair for which the suprathreshold interactions were comprehensively investigated, the pattern of basket cell firing was strongly influenced by the activity in the connected excitatory neurone. The basket cell was only effective in inhibiting spiny cell firing when the excitatory neurone was weakly driven.

Animals↗
PubMed1997

Calibration of an autocorrelation-based method for determining amplitude histogram reliability and quantal size.

1. We describe a method, based on autocorrelation and Monte Carlo simulation, for determining the likelihood that peaks in synaptic amplitude frequency histograms could have been a result of finite sampling from parent distributions that were unimodal. 2. The first step was to calculate an 'autocorrelation score' for the histogram to be tested. A unimodal distribution was fitted to the test histogram and subtracted from it. The resulting difference function was smoothed and its autocorrelation function calculated. The amplitude of the first (non-zero lag) peak in this autocorrelation function was taken as the autocorrelation score for that histogram. The score depends on the sharpness of the histogram peaks, the equality of their spacing and the number of trials. 3. The second stage was to generate large numbers of random samples, each of the same number of trials as the histogram, from a unimodal generator distribution of similar shape. The autocorrelation score was calculated for each sample and the proportion of samples with scores greater than the histogram gave the likelihood that the histogram peaks could have arisen by sampling artifact. 4. The method was calibrated using simulated non-quantal and quantal histograms with different signal-to-noise ratios and numbers of trials. For a quantal distribution with four peaks and a signal-to-noise ratio of 3, a sample size of about 500 trials was needed for 95% of samples to be distinguished from a non-quantal distribution. 5. The ability of the autocorrelation method to distinguish quantal from non-quantal distributions was compared against two conventional statistical tests, the chi 2 and the Kolmogorov-Smirnov goodness of fit tests. The autocorrelation method was more specific in extracting quantized responses. The Kolmogorov-Smirnov test in particular could not distinguish quantal distributions with multiple peaks even if the peaks were very sharp. 6. The improved discrimination of the autocorrelation method proved important when applied to experimental data recorded from hippocampal synapses. Of thirty-three histograms that were significantly different from smooth distributions by the autocorrelation method (P < 0.05), only seventeen were significantly different using the chi 2 test and only two when using the Kolmogorov-Smirnov test. 7. The autocorrelation method also gave an estimate of histogram peak spacing or quantal size. Using simulated quantal distributions, we showed that this estimate was likely to be correct within a few per cent for distributions that gave P < 0.01 by autocorrelation scoring.

Animals↗
PubMed1997

Assessment of the reliability or amplitude histograms from excitatory synapses in rat hippocampal CA1 in vitro.

1. Excitatory postsynaptic potentials (EPSPs) were evoked using minimal extracellular stimulation and recorded from pyramidal cells from the CA1 region of slices taken from adult rats and maintained in vitro. 2. Segments of data were selected that gave EPSP amplitude frequency histograms that showed approximately equally spaced peaks. Selection was performed either on the basis of stationarity of the EPSP mean and standard deviation, or on the trajectory of a graph of the (coefficient of variation)-2 against mean for the EPSP, or, in some cases, by trial and error. 3. For each histogram, we determined the likelihood that peaks of similar sharpness and equality of spacing could have arisen by sampling artifact from a smooth distribution, using a method based on autocorrelation and Monte Carlo simulation. 4. Thirty-three histograms were analysed. For twenty-six of these, the likelihood of sampling artifact was estimated at 1 in 100 or less, and for eleven histograms the likelihood was less than 1 in 1000. For the histogram with the clearest peaks, the likelihood was less than 1 in 350,000. Histograms judged to be reliable by this method could occur when the EPSP mean amplitude was changing. 5. We conclude that random sampling artifact is very unlikely to be the explanation for the peaks in our data histograms. It seems more likely that they are due to a quantal synaptic transmission mechanism with low quantal variability. 6. The autocorrelation method also gives a measure of the mean peak spacing, and hence the mean quantal size, for each histogram. Quantal sizes ranged from 93 to 285 microV, with a mean +/- S.D. of 172 +/- 47 microV. 7. From these quantal sizes and the EPSP mean amplitudes we calculated the mean number of quanta released per trial for each histogram. This ranged from 0.36 to 6.9, with a mean of 3.3 +/- 1.67.

Animals↗
PubMed1997

Quantal analysis of excitatory synapses in rat hippocampal CA1 in vitro during low-frequency depression.

1. We have performed a detailed quantal analysis of excitatory postsynaptic potentials (EPSPs) evoked by minimal extracellular stimulation in the CA1 region of slices of adult rat hippocampus maintained in vitro. 2. EPSPs were evoked at 2-5 Hz, and the eight that were analysed all showed at least a 50% depression of mean peak amplitude during recording. 3. EPSP amplitude fluctuations were analysed by three methods: the use of amplitude frequency histograms with clear and reliable peaks where available, graphs of the EPSP (coefficient of variation)-2 against EPSP mean, and analysis of EPSP mean and standard deviation assuming simple binomial statistics with the number of release sites (N) kept constant but the quantal size (Q) and the release probability (Pr) allowed to vary over time. 4. The results of the three analysis procedures were in good agreement. Seven EPSPs showed a substantial reduction in the mean number of quanta released per trial, and in three cases this was the predominant mechanism of the depression. Five EPSPs showed a substantial decrease in Q. Values for N ranged between 3 and 18, with a median of 6; Pr ranged between 0.14 and 0.81 and Q between 66 and 275 microV. 5. We used the Q estimates from the binomial method to correct the recorded EPSP amplitudes for changes in quantal size over time. For seven out of the eight EPSPs, this rescaling procedure allowed histograms with clear peaks to be obtained from longer runs of data, or improved the sharpness of the peaks in histograms from all the recorded data. The improvement in peak sharpness was assessed using an autocorrelation-based method. The correction was much less successful if the Q estimates were obtained with a variant of the binomial method in which Pr was held constant and N was allowed to vary. 6. The only simple explanation for the success of the correction procedure is that changes in quantal size were a major factor in obscuring peaks in histograms based on large numbers of trials, and that the quantal size estimates from the binomial method with N held constant were reasonably accurate. 7. We conclude that transmission at these synapses was quantal with relatively low quantal variance, but repetitive stimulation often induced substantial changes in the quantal parameters that might prevent the success of conventional quantal analysis approaches.

Animals↗
PubMed1997

The effects of synaptic noise on measurements of evoked excitatory postsynaptic response amplitudes.

Spontaneously occurring synaptic events (synaptic noise) recorded intracellularly are usually assumed to be independent of evoked postsynaptic responses and to contaminate measures of postsynaptic response amplitude in a roughly Gaussian manner. Here we derive analytically the expected noise distribution for excitatory synaptic noise and investigate its effects on amplitude histograms. We propose that some fraction of this excitatory noise is initiated at the same release sites that contribute to the evoked synaptic event and develop an analytical model of the interaction between this fraction of the noise and the evoked postsynaptic response amplitude. Recording intracellularly with sharp microelectrodes in the in vitro hippocampal slice preparation, we find that excitatory synaptic noise accounts for up to 70% of the intracellular recording noise, when inhibition is blocked pharmacologically. Up to 20% of this noise shows a significant correlation with the evoked event amplitude, and the behavior of this component of the noise is consistent with a model which assumes that each release site experiences a refractory period of approximately 60 ms after release. In contrast with classical models of quantal variance, our models predict that excitatory synaptic noise can cause the apparent variance of successive peaks in an excitatory synaptic amplitude histogram to decrease from left to right, and in some cases to be less than the variance of the measured noise.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Excitatory synaptic inputs to spiny stellate cells in cat visual cortex.

In layer 4 of cat visual cortex, the monocular, concentric receptive fields of thalamic neurons, which relay retinal input to the cortex, are transformed into 'simple' cortical receptive fields that are binocular and selective for the precise orientation, direction of motion, and size of the visual stimulus. These properties are thought to arise from the pattern of connections from thalamic neurons, although anatomical studies show that most excitatory inputs to layer 4 simple cells are from recurrently connected circuits of cortical neurons. We examined single fibre inputs to spiny stellate neurons. We examined single fibre inputs to spiny stellate neurons in slices of cat visual cortex, and conclude that thalamocortical synapses are powerful and the responses they evoke are unusually invariant for central synapses. However, the responses to intracortical inputs, although less invariant, are strong enough to provide most of the excitation to simple cells in vivo. Our results suggest that the recurrent excitatory circuits of cortex may amplify the initial feedforward thalamic signal, subserving dynamic modifications of the functional properties of cortical neurons.

Animals↗
PubMed1995

The variance of successive peaks in synaptic amplitude histograms: effects of inter-site differences in quantal size.

Variability in the measured amplitude of evoked synaptic events can arise from several factors, including: measurement noise, trial-to-trial variation in the amplitude of the response at a single release site, or variation between different release sites (inter-site variation) in the mean amplitude of the single quantal response. Classic (linear) models of variability include only the first two of these factors, although differences in the number of postsynaptic receptors or the degree of electrotonic attenuation for different release sites could cause substantial inter-site variations in quantal size. In this paper, the effect of inter-site variation on the variance of successive histogram peaks has been determined analytically and verified by computational studies. This effect is minimal at the edges of the histogram and contributes maximally to central peaks. Linear approximations to the variance of successive histogram peaks may therefore result in very poor fits to measured data if substantial inter-site variation in quantal size is involved. Our computational results indicate that for synaptic contacts with high release probabilities and substantial inter-site variation, the variance of histogram peaks will decrease with increasing quantal content.

Animals↗
PubMed1995

Synaptic plasticity: hippocampal LTP.

One of the most intensively studied forms of synaptic plasticity is long-term potentiation (LTP). The past year has seen further evidence advanced on both sides of the presynaptic/postsynaptic locus of expression debate, without an obvious path to reconcile the two views. Real progress has been made, however, in clarifying the possible role of nitric oxide as a retrograde messenger and the cellular location of its synthetic enzyme. Intriguing glimpses of the complex involvement of metabotropic glutamate receptors in the induction of LTP have also appeared.

Animals↗
PubMed1994

Detailed passive cable models of whole-cell recorded CA3 pyramidal neurons in rat hippocampal slices.

Tight-seal whole-cell recordings were made from cleaned somata of CA3 pyramidal cells deep in hippocampal slices from 19-21-d-old rats. The cells were filled with biocytin, and their voltage responses to short current pulses were recorded. After washout of initial sag, responses scaled linearly with injected current and were stable over time. The dendritic and axonal arbors of four cells were reconstructed and measured using light microscopy. Dendritic spines and axonal boutons were counted and the additional membrane area was incorporated into the relevant segments. The morphology of each neuron was converted into a detailed branching cable model by assuming values for specific membrane capacitance Cm and resistance Rm, and cytoplasmic resistivity Ri. These parameters were optimized for each cell by directly matching the model's response to that of the real cell by means of a modified weighted least-squares fitting procedure. By comparing the deviations between model and experimental responses to control noise recordings, approximate 95% confidence intervals were established for each parameter. If a somatic shunt was allowed, a wide range of possible Rm values produced acceptable fits. With zero shunt, Cm was 0.7-0.8 microFcm-2, Ri was 170-340 omega cm, and Rm ranged between 120 and 200 k omega cm2. The electrotonic lengths of the basal and oblique dendrites were 0.2-0.3 space constants, and those of the apical tufts were 0.4-0.7 space constants. The steady-state electrical geometry of these cells was therefore compact; average dendritic tip/soma relative synaptic efficacies were > 93% for the basal and oblique dendrites, and > 81% for the tufts. With fast transient synaptic inputs, however, the models produced a wide range of postsynaptic potential shapes and marked filtering of voltage-clamp currents.

Animals↗
PubMed1993

Solutions for transients in arbitrarily branching cables: I. Voltage recording with a somatic shunt.

An analytical solution is derived for voltage transients in an arbitrarily branching passive cable neurone model with a soma and somatic shunt. The response to injected currents can be represented as an infinite series of exponentially decaying components with different time constants and amplitudes. The time constants of a given model, obtained from the roots of a recursive transcendental equation, are independent of the stimulating and recording positions. Each amplitude is the product of three factors dependent on the corresponding root: one constant over the cell, one varying with the input site, and one with the recording site. The amplitudes are not altered by interchanging these sites. The solution reveals explicitly some of the parameter dependencies of the responses. An efficient recursive root-finding algorithm is described. Certain regular geometries lead to "lost" roots; difficulties associated with these can be avoided by making small changes to the lengths of affected segments. Complicated cells, such as a CA1 pyramid, produce many closely spaced time constants in the range of interest. Models with large somatic shunts and dendrites of unequal electrotonic lengths can produce large amplitude waveform components with surprisingly slow time constants. This analytic solution should complement existing passive neurone modeling techniques.

Animals↗
PubMed1993

Solutions for transients in arbitrarily branching cables: II. Voltage clamp theory.

Analytical solutions are derived for arbitrarily branching passive neurone models with a soma and somatic shunt, for synaptic inputs and somatic voltage commands, for both perfect and imperfect somatic voltage clamp. The solutions are infinite exponential series. Perfect clamp decouples different dendritic trees at the soma: each exponential component exists only in one tree; its time constant is independent of stimulating and recording position within the tree; its amplitude is the product of a factor constant over that entire tree and factors dependent on stimulating and recording positions. Imperfect clamp to zero is mathematically equivalent to voltage recording with a shunt. As the series resistance increases, different dendritic trees become more strongly coupled. A number of interesting response symmetries are evident. The solutions reveal parameter dependencies, including an insensitivity of the early parts of the responses to specific membrane resistivity and somatic shunt, and an approximately linear dependence of the slower time constants on series resistance, for small series resistances. The solutions are illustrated using a "cartoon" representation of a CA1 pyramidal cell and a two-cylinder + soma model.

Animals↗
PubMed1992

Dendritic morphology of pyramidal neurones of the visual cortex of the rat. IV: Electrical geometry.

Features of the dendritic morphology of pyramidal neurones of the visual cortex of the rat that are relevant to the development of models of their passive electrical geometry were investigated. The sample of 39 neurones that was used came from layers 2/3 and 5. They had been recorded from and injected intracellularly with horseradish peroxidase (HRP) in vitro as part of a previous study (Larkman and Mason, J. Neurosci 10:1407, 1990). These cells had been reconstructed and measured previously by light microscopy. The relationship between the diameters of parent and daughter dendrites during branching was examined. It was found that most dendrites did not closely obey the "3/2 branch power relationship" required for representation of the dendrites as single equivalent cylinders. Estimates of total neuronal membrane area ranged from 27,100 +/- 7,900 microns2 for layer 2/3 cells to 52,200 +/- 11,800 microns2 for thick layer 5 cells. Dendritic spines contributed approximately half the total membrane area. Both neuronal input resistance and the ratio of membrane time constant to input resistance were correlated with neuronal membrane area as measured anatomically. The relative electrical lengths of the different dendrites of individual neurones were investigated, by using simple transformations to take account of the differences in diameter and spine density between dendritic segments. A novel "morphotonic" transformation is described that represents the purely morphological component of electrotonic length. Morphotonic lengths can be converted into electrotonic lengths by division by a "morphoelectric factor" ([Rm/Ri]1/2). This procedure has the advantage of separating the steps involving anatomical and electrical parameters. These transformations indicated that the dendrites of the apical terminal arbor were much longer electrically than the basal or apical oblique dendrites. In relative electrical terms, most apical oblique trees arose extremely close to the soma, and terminated at similar distances to the basals. These results indicate that the dendrites of these pyramidal cells cannot be represented as single equivalent cylinders. The electrotonic lengths of the dendrites were calculated by using the electrical parameters specific membrane capacitance (Cm), intracellular resistivity (Ri), and specific membrane resistivity (Rm). Conventional values were assumed for Cm (1.0 muFcm-2) and Ri (100 omega cm), but three different Rm values were used for each cell. Two of these were within the conventionally accepted range (10,000-20,000 omega cm2), while the third value was an order of magnitude higher, in line with some recent evidence from modeling and whole-cell recording studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Electrophysiology of dopaminergic and non-dopaminergic neurones of the guinea-pig substantia nigra pars compacta in vitro.

1. The membrane properties of substantia nigra pars compacta neurones were studied using an in vitro slice preparation of guinea-pig midbrain. 2. Neurones were divided into two classes based on their electrophysiological properties: bursting neurones displayed a burst of several rapidly accommodating action potentials in response to relaxation of hyperpolarizing current injected through the microelectrode, while non-bursting neurones produced regularly spaced action potentials. These neuronal types were found to be electrophysiologically distinct from those recorded in the substantia nigra pars reticulata and the subthalamic nucleus. 3. Non-bursting neurones, which comprised ca 85% of the sampled cells, were characterized by a slow, pacemaker pattern of firing at rest, broad action potentials, a pronounced spike after-hyperpolarization, long membrane time constants, and strong transient outward and time-dependent inward rectification. 4. Bursting neurones, comprising ca 15% of the sample, displayed rapid firing rates at rest, fast action potentials, a shallow spike after-hyperpolarization and briefer membrane time constants. All of these parameters were significantly different from those of the non-bursting type. Bursting neurones lacked transient outward or time-dependent inward rectification. 5. Both types of cells were capable of generating pronounced calcium-dependent, low-threshold spikes in the presence of tetrodotoxin (TTX). However, only the non-bursting type displayed calcium-dependent rhythmic oscillations in membrane potential near resting potential in the presence of TTX. The firing rate, action potential shape and after-hyperpolarization of non-bursting neurones were strongly influenced by calcium-dependent currents. 6. The majority of cells were injected with biocytin, which allowed morphological reconstruction of the neurones and confirmation of their location within the pars compacta. Non-bursting neurones had variable soma shapes and their dendrites were mostly directed in a medio-lateral direction. Many cells extended some of their dendrites into the pars reticulata. Bursting neurones were mainly fusiform in shape with their dendrites oriented in a medio-lateral direction; a few had dendrites extending into the pars reticulata. 7. Thirty-six neurones were also double labelled using a combination of biocytin or Lucifer Yellow injection with tyrosine hydroxylase (TH) immunohistochemistry. Non-bursting neurones all displayed TH immunofluorescence, while none of the bursting neurones were TH positive.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗