Receptive-field construction in cortical inhibitory interneurons.

In the somatosensory 'barrel' cortex (where each barrel represents an individual whisker) the receptive fields of cortical spiny neurons show considerable specificity for the direction of whisker displacement, as do the receptive fields of thalamocortical (TC) neurons that provide input to the barrels. In contrast, putative fast-spike inhibitory interneurons in layer 4 of the barrel cortex lack directional preference, but are exquisitely sensitive to low stimulus intensities. Here we show, in adult rabbits, that these sensitive and broadly tuned inhibitory receptive fields are generated by an unselective pooling of convergent functional inputs from topographically aligned TC neurons with very diverse response properties.

The impact of 'bursting' thalamic impulses at a neocortical synapse.

Considerable effort has gone into understanding the mechanisms underlying high-frequency 'bursting' of thalamocortical impulses, their sensory information content and their involvement in perception. However, little is known about the influence of such impulses on their cortical targets. Here we follow bursting thalamic impulses to their terminus at the thalamocortical synapse of the awake rabbit, and examine their influence on a class of somatosensory cortical neurons. We show that thalamic bursts potently activate cortical circuits. Initial impulses of each burst have a greatly enhanced ability to elicit cortical action potentials, and later impulses in the burst further raise the probability of eliciting spikes. In some cases, multiple cortical spikes result from a single burst. Moreover, we show that the interval preceding each burst is crucial for generating the enhanced cortical response. The powerful activation of neocortex by thalamocortical bursts is fully consistent with an involvement of these impulses in perceptual/attentional processes.

The influence of single VB thalamocortical impulses on barrel columns of rabbit somatosensory cortex.

Extracellular recordings were obtained from single neurons in ventrobasal (VB) thalamus of awake rabbits while field potentials were recorded at various depths within topographically aligned and nonaligned barrel columns of somatosensory cortex (S1). Spike-triggered averages of cortical field potentials were obtained following action potentials in thalamic neurons. Action potentials in a VB neuron elicited a cortical response within layer 4 with three distinct components. 1) A biphasic, initially positive response (latency <1 ms) was interpreted to reflect activation of the VB axon terminals (the AxTP). This response was not affected by infusion of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist within the barrel. In contrast, later components of the response were completely eliminated and were interpreted to reflect focal synaptic potentials. 2) A negative potential [focal synaptic negativity (FSN)] occurred at a mean latency of 1.65 ms and lasted approximately 4 ms. This response had a rapid rise time ( approximately 0.7 ms) and was interpreted to reflect monosynaptic excitation. 3) The third component was a positive potential (the FSP), with a slow rise time and a half-amplitude duration of approximately 30 ms. The FSP showed a weak reversal in superficial cortical layers and was interpreted to reflect di/polysynaptic inhibition. The amplitudes of the AxTP, the FSN, and the FSP reached a peak near layer 4 and were highly attenuated in both superficial and deep cortical layers. All components were attenuated or absent when the cortical electrode was missaligned from the thalamic electrode by a single cortical barrel. Deconvolution procedures revealed that the autocorrelogram of the presynaptic VB neuron had very little influence on either the amplitude or duration of the AxTP or the FSN, and only a minor influence (mean, 11%) on the amplitude of the FSP. We conclude that individual VB thalamic impulses entering a cortical barrel engage both monosynaptic excitatory and di/polysynaptic inhibitory mechanisms. Putative inhibitory interneurons of an S1 barrel receive a highly divergent/convergent monosynaptic input from the topographically aligned VB barreloid, and this results in sharp synchrony among these interneurons. We suggest that single-fiber access to disynaptic inhibition is facilitated by this sharp synchrony, and that the FSP reflects a consequent synchronous wave of feed-forward inhibition within the S1 barrel.

Cross-correlation analysis of neuron connections in the cerebellum of conscious rabbits.

Cross-interval and cross-correlation analysis of neuron activity was used to study cell interactions in the cerebellar vermis of conscious rabbits. The cross-correlation method, based on post-synaptic potentials (PSP) from one member of a pair of neurons, supplements the cross-interval analysis used for evaluating the interactions of neurons in terms of action potentials. A total of 16 neuron pairs were analyzed, in which the activity of one neuron was recorded intracellularly and that of the other extra- or intracellularly. Interactions were observed in 10 pairs. Most pairs showed inhibitory interactions. Pairs with inhibitory interactions included those in which the activity of one or both neurons contained complex spikes. Also of interest was the analysis of connections in which influences were excitatory in one direction and inhibitory in the other. In these cases, neuron discharges were invariably simple spikes. Variability and plasticity in the output signals of Purkinje cells were greater than the variability and plasticity of the common inputs to Purkinje cells.

[Cross-correlational analysis of the neuronal connections of the cerebellum in the waking rabbit]. / Krosskorreliatsionnyi analiz sviazei neironov mozzhechka bodrstvuiushchego krolika.

The methods of cross-interval and crosscorrelation analysis were used to study interneuronal connections in cerebellar vermis in awake rabbit. Crosscorrelation, or spike-triggering method, complemented the analysis of cross-intervals which estimated the neuronal interaction comparing spike sequences as point processes. Among 16 neuronal pairs recorded intra- or extracellularly 10 pairs were considered as interconnected. Inhibitory interconnections dominated. The inhibitory neuronal interconnections were revealed in pairs with complex spikes. Neurons which constituted pairs with reciprocal excitatory-inhibitory interaction fired only simple spikes. The variability and plasticity of common inputs to Purkinje cells were seemingly lower than those of direct connections which probably transmitted the output signals of Purkinje cells.

Prolonged postsynaptic changes in the sensorimotor cortex of the awake rabbit in response to stimulation of fibers of the white matter of the new cortex and the corpus callosum.

The postsynaptic changes in the focal potentials of the sensorimotor cortex of the awake rabbit was investigated in this study following tetanization of the corpus callosum and the white matter. Stimulation of these structures was carried out during testing. A prolonged (hour-long) increase in the amplitude of the responses was observed in some of the experiments following tetanization, as compared with the control prior tetanization. Just as long a decrease in the amplitude of the responses tested developed in a number of experiments in the posttetanic period. It was concluded that prolonged plastic changes can occur in different directions in the sensorimotor cortex of the awake rabbit.

Reliability of quantal parameter estimates and their changes during long-term potentiation in guinea pig hippocampal slices.

Previously we found increases in quantal content (m) and smaller increases in quantal size (v) during long-term potentiation (LTP) in CA1 of hippocampal slices. However, the validity of the deconvolution technique was questioned recently because v estimates correlated with the noise standard deviation (Sn). In computer simulations we show a double-step dependence of v on Sn/v: correct v estimates (within +/- 20%) for Sn/v < or = 0.5 and overestimates (correlated with Sn) for Sn/v > 0.5. A novel 'noise addition' procedure is proposed for accepting reliable solutions on the basis of the double-step relationship between v and Sn. Quantal analysis of LTP for more reliable solutions confirmed previous conclusions.

Quantal parameters of "minimal" excitatory postsynaptic potentials in guinea pig hippocampal slices: binomial approach.

Binomial distributions of amplitudes of excitatory postsynaptic potentials (EPSPs) mixed with Gaussian noise were simulated. The objective of Monte Carlo simulations was, firstly, to study influences of sampling size (N) and noise standard deviation (Sn) on estimates of mean quantal content (m), quantal size (v) and binomial parameters (n and p) by four methods of quantal analysis (histogram, variance, failures and combined method) based on the binomial model and, secondly, to modify these methods on the basis of comparison of estimated with simulated parameters. Reliable estimates (within +/- 10% of the simulated values) were obtained for large sample sizes (N = 500-1000) with Sn less than or equal to v by the histogram (deconvolution) method and with Sn less than or equal to 2v by the other three methods. Similar results were obtained by averages from about 10 simulations if smaller samples were used (N = 50-200). In electrophysiological experiments on slices, "minimal" EPSPs were recorded from CA1 pyramidal cells after low-intensity stimuli to stratum radiatum or stratum oriens. Amplitudes of minimal EPSPs fluctuated in a manner predicted by the quantum hypothesis. Amplitude distributions of EPSPs in the non-facilitated state were adequately described either by binomial statistics with an average p equal to about 0.4 (a range of 0.3-0.7) and an average n of about 3 (range 2-6) or by Poisson statistics with m of about 1. The quantal analysis suggests that typical values of m and v for a single activated fibre in stratum radiatum might be about 0.5-1 and 300-400 microV, respectively, with low p (0.1-0.3) and n (2-4). However, the estimates of binomial parameters should be considered as coarse approximations in view of the simulation results and a possible nonuniformity of parameter p. The comparison of results of various methods based on the binomial model, in both simulation and physiological experiments, indicates the reliability of estimates of basic quantal parameters (m and v) under realistic conditions of physiological experiments. The methods are considered to be sufficiently sensitive to make use of them for studies on mechanisms of long-term synaptic plasticity.

[Prolonged posttetanic changes in the sensorimotor cortex of the waking rabbit in response to stimulation of the fibers of the substantia alba in the neocortex and corpus callosum]. / Dlitel'nye posttetanicheskie izmeneniia v sensomotornoi kore bodrstvuiushchego krolika v otvet na stimuliatsiiu volokon belogo veshchestva novoi kory i mozolistogo tela.

Study of posttetanic changes in the sensorimotor cortex of the alert rabbit in response to stimulation of callosal fibres of the white matter have shown that in comparison to the control level either a prolonged increase (potentiation) of the tested evoked potentials to the stimulation of the same structures takes place, or the amplitude of the tested evoked potentials decreases (depression). Both processes can take place simultaneously in different layers of the cortex.

Quantal analysis of long-term potentiation of "minimal" excitatory postsynaptic potentials in guinea pig hippocampal slices: binomial approach.

"Minimal" excitatory postsynaptic potentials (EPSPs) were recorded from 13 neurones in area CA1 of guinea pig hippocampal slices after double-pulse stimulation of stratum radiatum (str. rad.) and stratum oriens (str. or.). Amplitudes of EPSPs significantly increased in 8 neurones 5 to 55 min after 9 tetanizations in str. rad.. The increase was considered to represent long-term potentiation (LTP). Altogether 26 EPSPs (42 post-tetanic regions) were statistically analysed by four methods of the quantum hypothesis assuming the binomial model of transmitter release: the deconvolution (histogram), the variance, the failures, and the combined (variance-failures) methods. The mean quantal content (m) significantly increased after LTP induction according to all methods used. Quantal size (v) also tended to increase but according to some methods, the increase was not statistically significant and it did not correlate with LTP magnitude. However, for an EPSP subset with a LTP magnitude of less than 1.55, the increase in v correlated with LTP magnitude, whereas the increase in m did not. The relative contribution of the increase in v to LTP magnitude was larger for cases with small LTP than for the whole EPSP set. In general, the increase in m corresponds to previous studies and favours the presynaptic location of major mechanisms of LTP maintenance, i.e. an increase in the average number of transmitter quanta released by each presynaptic volley. The post-tetanic increase in v might reflect some additional mechanisms which presumably include an increase in the amount of transmitter in one quantum.

Analysis of fluctuations of "minimal" excitatory postsynaptic potentials during long-term potentiation in guinea pig hippocampal slices.

In previous studies, quantal analysis assuming a simple binomial model has shown that long-term potentiation (LTP) is accompanied by an increase in both mean quantal content (m) and quantal size (v), whereby the increase in m predominates. In the present study, "compound" binomial distributions with variable probabilities were convolved with Gaussian distributions in computer experiments to simulate amplitude histograms of intracellular excitatory postsynaptic potentials (EPSPs). A deconvolution procedure assuming equal "quantal" separation (v) between discrete components, but without assuming binomial statistics, was applied to the simulated distributions to determine v. It was found that with a small ratio of standard deviation of noise to v (Sn/v less than 0.4), a reliable estimate of v can be obtained even for small samples (N = 100). When Sn/v was larger (0.4-0.6), approximate v estimates (within +/- 10-20% of the simulated v) could be obtained by averaging estimates from about 10 small samples (N = 100). "Minimal" EPSPs were recorded in area CA1 of guinea pig hippocampal slices. 37 EPSP amplitude samples of 9 neurones were measured before and up to 55 min after 10 tetanizations of stratum radiatum. In accordance with the previous data, the increase in v accounted for only about 10% of the average post-tetanic increase in EPSP amplitude and was not correlated with the latter. However, for an EPSP subset with small LTP magnitude, the increase in v accounted for an essential part of the LTP magnitude while the increase in m did not correlate with it. The results are in agreement with previous data obtained in the context of the simple binomial model and are interpreted as indicating primarily a presynaptic mechanism of LTP maintenance. The results suggest two types of synaptic mechanism of LTP maintenance related to the increases in m and v, respectively. The latter mechanism is saturated at about 10 to 30% increase in post-tetanic amplitude above the pre-tetanic EPSP amplitude.

[A comparison of statistical methods for quantal analysis in computer and physiological experiments]. / Sopostavlenie statisticheskikh metodov kvantovogo analiza v komp'iuternom i fiziologicheskom éksperimentakh.

Amplitude distributions of postsynaptic potentials were simulated in computer experiments on the basis of binomial statistics. Influences of the sample size (N) and noise standard deviation (Sn) on the determination of the quantal content (m) and quantal size (v) were studied. Four methods of the quantal parameter estimation were modified and used: histogram, variance, failure and combined method. Three last methods gave satisfactory estimations (within +/- 10%) at N = 500-1000 and Sn less than 2v. The histogram method was adequate at Sn less than or equal to v. Similar results were obtained at N = 50-200, when the experiment was repeated about ten times. Applicability of similar methods was confirmed by the analysis of an intracellular record of inhibitory postsynaptic potentials (N = 1333) from the sensorimotor cortex of rabbit.

[Electrophysiologic characteristics of the neurons in the rabbit sensorimotor cortex]. / Elektrofiziologicheskie kharakteristiki neironov sensomotornoi kory krolikov.

Electrical parameters of the sensomotor cortex neurons were studied in unanesthetized rabbits. The values of mean interspike membrane potential, spike threshold, spike "failures" and duration were computed in 800-spike epochs. Scatter diagrams and the data obtained for the parameters provided additional usable information.

[Comparative analysis of the statistical parameters of synaptic transmission of central neurons in the snail Helix lucorum and in the rabbit]. / Sravnitel'nyi analiz statisticheskikh parametrov sinapticheskoi peredachi tsentral'nykh neironov ulitki Helix lucorum i krolika.

Comparative analysis of the parameters of synaptic transmission in the central synapses of the snail (parietal ganglia) and in the brain of rabbit (hippocamp and sensorymotor cortex) has been made. Both differences and common features were revealed in synaptic organization of these two objects. Functional re-arrangements may alleviate differences between central synapses of the snail and rabbit. It is concluded that evolution of the central nervous system involved mainly the decrease of the effectiveness of separate synapses at the cost of the decrease of the number of quanta of the released transmitter and the increase of the number of various synaptic connections on each neuron.

[Elementary polysynaptic potentials of hippocampal neurons]. / Elementarnye postsinapticheskie potentsialy gippokampal'nykh neironov.

Synaptic connections of 26 pairs of hippocampal neurons were studied in nonanesthetized rabbits by spike-triggered averaging of intracellularly recorded activity. Synchronized activity was detected in 5 pairs and considered to represent common inputs to the neurons recorded. Hyperpolarizing or depolarizing potentials with 3--4 ms latency were revealed in 3 additional pairs. These potentials are considered to be individual postsynaptic potentials (PSPs) evoked in the target neuron by spikes of the adjacent (0.5--2 mm apart) neuron. A quantum analysis of the individual PSPs was performed. The mean quantum content (0.27--0.65) and quantum size (35--200 mkV) were found to be of the same order as those of the excitatory PSPs previously recorded after intracerebral stimulation. It is concluded that most hippocampal synapses are of low efficacy.