Deviation of spontaneous firing in frog medullar auditory units from the renewal point process

Statistical characteristics of spontaneous activity (distribution of interspike intervals, hazard function, autocorrelation function, autocorrelation function for the process with mixed intervals, and interdependence between adjoining intervals) were analyzed for 123 neurons of the frog medullar dorsal nucleus (homolog of the mammalian cochlear nucleus). In the majority of cells, this activity was distinct from the Poisson process, and firing periodicity was noticed in some cases. In addition, deviations of the spontaneous activity from the renewal process were usually observed. Weak yet reliable positive interspike-interval correlation was typical of most neurons; however, a negative correlation between short adjoining intervals was recorded for some units. These data suggest the effects of memory in the activity of single neurons of the auditory system.     

Deviations of spontaneous firing in the cochlear nucleus of the frog from the renewal point process

The analysis of statistical characteristics of spontaneous activity (distribution of interpulse intervals, hazard function, autocorrelation function, autocorrelation function for a process with shifted intervals, interdependence between adjoining intervals) for 123 units located in the cochlear nucleus of the frog has been performed. In the majority of cells, this activity was distinct from the poissonic process, and in some cases firing periodicity was noticed. Besides, deviations of the spontaneous activity from the renewal process were usually observed. A reliable positive correlation of interpulse intervals was typical for the majority of the units, though in some cases a negative correlation of short adjoining intervals was revealed. The data indicate the occurrence of effects of memory in the activity of single units of the acoustical system.     

Spontaneous activity of auditory cortical neurons of waking cats at rest and during defensive conditioning

The results of a computerized statistical analysis of 366 realizations of spontaneous spike activity of 181 neurons in the primary auditory cortex (area 50) of waking cats at rest and during defensive conditioning are described. In both situations the parameters of spontaneous activity of most neurons differed from those of a random flow. Conditioning led, on the one hand, to a stable increase in the frequency of spontaneous activity in intertrial periods and, on the other hand, judging from changes in the mean firing rate, the coefficients of variation of the length of the interspike intervals, the histograms of their distribution, and also the increase in the number of neurons with different forms of correlation between interspike intervals, to an increase in its stability (degree of organization).A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 3, pp. 227–238, May–June, 1978.     

Auditory units in the medulla of the marsh frog with unusual patterns of spontaneous activity

Statistical properties of spontaneous firing were studied in 79 single auditory units located in the dorsal medullar (cochlear) nucleus of unanaesthetized curarized marsh frogs (Rana ridibunda). The great majority of these units showed irregular spontaneous activity with mean rates in the range 1–30 spikes · s^–1. In 53% of the cells the auto-renewal functions of the spontaneous activity monotonically rose to an asymptotic value, but 41% of the cells produced auto-renewal functions which showed a pronounced peak after a dead-time period. Five low-frequency auditory neurons revealed periodic firing in the absence of controlled stimuli. The preferred period did not correspond to the unit's best frequency but demonstrated a modest correlation with the best modulation frequency of the unit's response to amplitude-modulated tones and with the duration of the after-onset dip in peri-stimulus time histograms.Abbreviations AM amplitude modulation - ARF auto-renewal function - DMN dorsal medullar nucleus - PST peristimulus time - SA spontaneous activity - TID time interval distribution - RMG response modulation gain     

Some properties of auditory neuron’s model trained by firing caused by tones modulated by low-frequency noise

In many sensory systems the formation of burst firing can be observed along a way from the periphery to the central nuclei. We investigate the putative transformation of spontaneous activity in the auditory pathway using a neuron model trained by real firing recorded in the auditory nuclei of the frog. The model has 200 separate inputs (neuronal spines). It is supposed that every spine is a coincidence detector. Its output (synaptic potential) sharply increases at emergence of the precisely certain interpulse interval in an input pulse sequence. If the total synaptic potentials excess a threshold, the model generates output spike, which changes weight of all spines according to the simplified Hebb principle. The model was trained by real firing caused in the auditory nuclei of the frog by tones modulated by low-frequency noise in the frequency ranges of 0–15 Hz, 0–50 Hz or 0–150 Hz. After that training the synaptic weights of every spine essentially changed. Thus, along with some increase of weights of spines tuned to boundary frequencies of modulating noise, the most characteristic change was the emphasizing weights of spines tuned to short interpulse intervals. As a result the spontaneous activity passed through the trained model became much more bursting. Efficiency of a signal transmission in model was higher when input spontaneous activity of real cells contains bursts of spikes. Results of modeling are discussed in connection with modern physiological data demonstrating the functional advantage of bursting.     

On the dynamics of the spontaneous activity in neuronal networks

Most neuronal networks, even in the absence of external stimuli, produce spontaneous bursts of spikes separated by periods of reduced activity. The origin and functional role of these neuronal events are still unclear. The present work shows that the spontaneous activity of two very different networks, intact leech ganglia and dissociated cultures of rat hippocampal neurons, share several features. Indeed, in both networks: i) the inter-spike intervals distribution of the spontaneous firing of single neurons is either regular or periodic or bursting, with the fraction of bursting neurons depending on the network activity; ii) bursts of spontaneous spikes have the same broad distributions of size and duration; iii) the degree of correlated activity increases with the bin width, and the power spectrum of the network firing rate has a 1/f behavior at low frequencies, indicating the existence of long-range temporal correlations; iv) the activity of excitatory synaptic pathways mediated by NMDA receptors is necessary for the onset of the long-range correlations and for the presence of large bursts; v) blockage of inhibitory synaptic pathways mediated by GABA(A) receptors causes instead an increase in the correlation among neurons and leads to a burst distribution composed only of very small and very large bursts. These results suggest that the spontaneous electrical activity in neuronal networks with different architectures and functions can have very similar properties and common dynamics.     

5,7-双羟色胺损毁大鼠中缝背核后底丘脑核的神经活动增强

采用玻璃微电极在体细胞外记录法,观察了5,7-双羟色胺(5,7-dihydroxytryptamine,5,7-DHT)损毁大鼠中缝背核(dorsalraphenucleus,DRN)后,底丘脑核(subthalamicnucleus,STN)神经元电活动的变化。结果发现,对照组和DRN损毁组大鼠STN神经元的放电频率分别是(6.93±6.55)Hz和(11.27±9.31)Hz,DRN损毁组大鼠的放电频率显著高于对照组(P<0.01)。在对照组大鼠,13%的神经元呈现规则放电,46%为不规则放电,41%为爆发式放电;而在DRN损毁组大鼠,具有规则、不规则和爆发式放电的神经元比例分别为9%、14%和77%,爆发式放电的STN神经元比例明显高于对照组(P<0.01)。结果显示,DRN损毁后大鼠STN神经元的放电频率增高,爆发式放电增多,提示在正常大鼠DRN抑制STN神经元的活动。     

Neuronal Activity of the Subthalamic Nucleus in Patients with Parkinson’s Disease

The discharge activity of 637 neurons of the human subthalamic nucleus (STN), which were extracellularly recorded during twelve stereotactic surgeries in patients with Parkinson’s disease, has been analyzed. On the basis of the parameters of interspike intervals (ISIs), we have distinguished three major patterns of spontaneous neuronal activity: bursting neurons, regular tonic and irregular tonic neurons. Parametric analysis has enabled us to determine the values of basic parameters in the activity of these three distinguished types of neurons. It has been shown that the representativeness and the activity parameters of three different patterns change in the dorsoventral direction of the STN from the motor to the associative regions. The results will allow researchers to perform targeted search of pathological neuronal activity patterns associated with the motor symptoms of Parkinsonism.     

Stochastic model neuron without resetting of dendritic potential: application to the olfactory system

A two-dimensional neuronal model, in which the membrane potential of the dendrite evolves independently from that at the trigger zone of the axon, is proposed and studied. In classical one-dimensional neuronal models the dendritic and axonal potentials cannot be distinguished, and thus they are reset to resting level after firing of an action potential, whereas in the present model the dendritic potential is not reset. The trigger zone is modelled by a simplified leaky integrator (RC circuit) and the dendritic compartment can be described by any of the classical one-dimensional neuronal models. The new model simulates observed features of the firing dynamics which are not displayed by classical models, namely positive correlation between interspike intervals and endogenous bursting. It gives a more natural account of features already accounted for in previous models, such as the absence of an upper limit for the coefficient of variation of intervals (i.e. irregular firing). It allows the first- and second-order neurons of the olfactory system to be described with the same basic assumptions, which was not the case in one-point models. Nevertheless it keeps the main qualitative properties found previously, such as the existence of three regimens of firing with increasing stimulus concentration and the sigmoid shape of the firing frequency of firstorder neurons as a function of the logarithm of stimulus concentration.     

Gradients and modulation of K(+) channels optimize temporal accuracy in networks of auditory neurons

Accurate timing of action potentials is required for neurons in auditory brainstem nuclei to encode the frequency and phase of incoming sound stimuli. Many such neurons express "high threshold" Kv3-family channels that are required for firing at high rates (> -200 Hz). Kv3 channels are expressed in gradients along the medial-lateral tonotopic axis of the nuclei. Numerical simulations of auditory brainstem neurons were used to calculate the input-output relations of ensembles of 1-50 neurons, stimulated at rates between 100-1500 Hz. Individual neurons with different levels of potassium currents differ in their ability to follow specific rates of stimulation but all perform poorly when the stimulus rate is greater than the maximal firing rate of the neurons. The temporal accuracy of the combined synaptic output of an ensemble is, however, enhanced by the presence of gradients in Kv3 channel levels over that measured when neurons express uniform levels of channels. Surprisingly, at high rates of stimulation, temporal accuracy is also enhanced by the occurrence of random spontaneous activity, such as is normally observed in the absence of sound stimulation. For any pattern of stimulation, however, greatest accuracy is observed when, in the presence of spontaneous activity, the levels of potassium conductance in all of the neurons is adjusted to that found in the subset of neurons that respond better than their neighbors. This optimization of response by adjusting the K(+) conductance occurs for stimulus patterns containing either single and or multiple frequencies in the phase-locking range. The findings suggest that gradients of channel expression are required for normal auditory processing and that changes in levels of potassium currents across the nuclei, by mechanisms such as protein phosphorylation and rapid changes in channel synthesis, adapt the nuclei to the ongoing auditory environment.     

Effect of thyroliberin on membrane potential and pattern of spontaneous activity of neurons of the respiratory center in rats in vitro

On frontal brainstem slices of rat by means of whole-clamp recordings, we investigated effects of TRH (10(-8) [symbol: see text]) on membrane potential and firing pattern of the neurones in ventrolateral area of the solitary tract nucleus and pre-Botzinger complex. TRH induced a membrane depolarisation and an increase in spontaneous activity of the respiratory centre neurones. After TRH administration, a shortening of time intervals between the beginning of bursts was found in bursting neurones of the pre-Botzinger complex. In some silent neurones, TRH elicited appearance of firing activity, so the silent neurones of the solitary tract nucleus were transformed into tonic while the silent pre-Botzinger complex neurones were transformed into bursting ones. Thus, there is a direct regulatory effect of TRH on the respiratory centre neurones at the level of their membrane.     

Patterns of spontaneous activity in single rat olfactory receptor neurons are different in normally breathing and tracheotomized animals

Spontaneous firing of olfactory receptor neurons (ORNs) was recently shown to be required for the survival of ORNs and the maintenance of their appropriate synaptic connections with mitral cells in the olfactory bulb. ORN spontaneous activity has never been described or characterized quantitatively in mammals. To do so we have made extracellular single unit recordings from ORNs of freely breathing (FB) and tracheotomized (TT) rats. We show that the firing behavior of TT neurons was relatively simple: they tended to fire spikes at the same average frequency according to purely random (Poisson) or simple (Gamma or Weibull) statistical laws. A minority of them were bursting with relatively infrequent and short bursts. The activity of FB neurons was less simple: their firing rates were more diverse, some of them showed trends or were driven by breathing. Although more of them were regular, only a minority could be described by simple laws; the majority displayed random bursts with more spikes than the bursts of TT neurons. In both categories bursts and isolated spikes (outside bursts) occurred completely at random. The spontaneous activity of ORNs in rats resembles that of frogs, but is higher, which may be due to a difference in body temperature. These results suggest that, in addition to the intrinsic thermal noise, spontaneous activity is provoked in part by mechanical, thermal, or chemical (odorant molecules) effects of air movements due to respiration, this extrinsic part being naturally larger in FB neurons. It is suggested that spontaneous activity may be modulated by respiration. Because natural sampling of odors is synchronized with breathing, such modulation may prepare and keep olfactory bulb circuits tuned to process odor stimuli.     

Leydig neuron activity modulates heartbeat in the medicinal leech

1. Leydig neurons fire spontaneously at low rates (less than 4 Hz), but their activity increases with mechanical stimulation or electrical stimulation of mechanosensory neurons. These conditions also cause acceleration of bursting in heart motor neurons. 2. The firing rate of Leydig cells was found to regulate heart rate in chains of isolated ganglia. When Leydig neurons were made to fire action potentials at relatively high frequencies (ca. 5-10 Hz), however, heart motor neurons ceased bursting and were either silenced or fired erratically. 3. Firing of Leydig neurons at high rates caused bilateral heart interneurons of ganglia 3 or 4 to fire tonically rather than in their normal alternating bursts Tonic firing of these heart interneurons accounts for the prolonged barrages of ipsps recorded in heart motor neurons and the disruption of their normal cyclic activity. 4. Preventing spontaneous activity of Leydig neurons with injected currents in isolated ganglia caused deceleration of the heartbeat rhythm but did not halt oscillation. 5. Electrical stimulation of peripheral nerve roots with Leydig neuron activity suppressed in isolated ganglia caused acceleration of heart rate.     

Management of synchronized network activity by highly active neurons

Increasing evidence supports the idea that spontaneous brain activity may have an important functional role. Cultured neuronal networks provide a suitable model system to search for the mechanisms by which neuronal spontaneous activity is maintained and regulated. This activity is marked by synchronized bursting events (SBEs)--short time windows (hundreds of milliseconds) of rapid neuronal firing separated by long quiescent periods (seconds). However, there exists a special subset of rapidly firing neurons whose activity also persists between SBEs. It has been proposed that these highly active (HA) neurons play an important role in the management (i.e. establishment, maintenance and regulation) of the synchronized network activity. Here, we studied the dynamical properties and the functional role of HA neurons in homogeneous and engineered networks, during early network development, upon recovery from chemical inhibition and in response to electrical stimulations. We found that their sequences of inter-spike intervals (ISI) exhibit long time correlations and a unimodal distribution. During the network's development and under intense inhibition, the observed activity follows a transition period during which mostly HA neurons are active. Studying networks with engineered geometry, we found that HA neurons are precursors (the first to fire) of the spontaneous SBEs and are more responsive to electrical stimulations.     

Effects of coagulation of thelocus coeruleus and pontine raphe nuclei on the background activity recorded from the rat cerebellar fastigial nucleus neurons

Simultaneous or separate coagulation of thelocus coeruleus (LC) and the pontine raphe nucleus (PRN) results in a significant increase of irregular-type background activity in the cerebellar fastigial nucleus neurons. There are also considerable changes in the dynamics of impulse sequences, in particular, the number of neurons with random interpulse intervals markedly increases. Destruction of theLC and/or PRN is followed by a marked drop in the mean frequency of discharges in the neurons of the fastigial nucleus.Neirofiziologiya/Neurophysiology, Vol. 26, No. 6, pp. 437–442, November–December, 1994.     

Predicting the Responses of Repetitively Firing Neurons to Current Noise

We used phase resetting methods to predict firing patterns of rat subthalamic nucleus (STN) neurons when their rhythmic firing was densely perturbed by noise. We applied sequences of contiguous brief (0.5–2 ms) current pulses with amplitudes drawn from a Gaussian distribution (10–100 pA standard deviation) to autonomously firing STN neurons in slices. Current noise sequences increased the variability of spike times with little or no effect on the average firing rate. We measured the infinitesimal phase resetting curve (PRC) for each neuron using a noise-based method. A phase model consisting of only a firing rate and PRC was very accurate at predicting spike timing, accounting for more than 80% of spike time variance and reliably reproducing the spike-to-spike pattern of irregular firing. An approximation for the evolution of phase was used to predict the effect of firing rate and noise parameters on spike timing variability. It quantitatively predicted changes in variability of interspike intervals with variation in noise amplitude, pulse duration and firing rate over the normal range of STN spontaneous rates. When constant current was used to drive the cells to higher rates, the PRC was altered in size and shape and accurate predictions of the effects of noise relied on incorporating these changes into the prediction. Application of rate-neutral changes in conductance showed that changes in PRC shape arise from conductance changes known to accompany rate increases in STN neurons, rather than the rate increases themselves. Our results show that firing patterns of densely perturbed oscillators cannot readily be distinguished from those of neurons randomly excited to fire from the rest state. The spike timing of repetitively firing neurons may be quantitatively predicted from the input and their PRCs, even when they are so densely perturbed that they no longer fire rhythmically.     

Distinct neuronal types contribute to hybrid temporal encoding strategies in primate auditory cortex

Studies of the encoding of sensory stimuli by the brain often consider recorded neurons as a pool of identical units. Here, we report divergence in stimulus-encoding properties between subpopulations of cortical neurons that are classified based on spike timing and waveform features. Neurons in auditory cortex of the awake marmoset (Callithrix jacchus) encode temporal information with either stimulus-synchronized or nonsynchronized responses. When we classified single-unit recordings using either a criteria-based or an unsupervised classification method into regular-spiking, fast-spiking, and bursting units, a subset of intrinsically bursting neurons formed the most highly synchronized group, with strong phase-locking to sinusoidal amplitude modulation (SAM) that extended well above 20 Hz. In contrast with other unit types, these bursting neurons fired primarily on the rising phase of SAM or the onset of unmodulated stimuli, and preferred rapid stimulus onset rates. Such differentiating behavior has been previously reported in bursting neuron models and may reflect specializations for detection of acoustic edges. These units responded to natural stimuli (vocalizations) with brief and precise spiking at particular time points that could be decoded with high temporal stringency. Regular-spiking units better reflected the shape of slow modulations and responded more selectively to vocalizations with overall firing rate increases. Population decoding using time-binned neural activity found that decoding behavior differed substantially between regular-spiking and bursting units. A relatively small pool of bursting units was sufficient to identify the stimulus with high accuracy in a manner that relied on the temporal pattern of responses. These unit type differences may contribute to parallel and complementary neural codes.

Neurons in auditory cortex show highly diverse responses to sounds. This study suggests that neuronal type inferred from baseline firing properties accounts for much of this diversity, with a subpopulation of bursting units being specialized for precise temporal encoding.     

Spontaneous unit activity of the monkey caudate nucleus under chronic experimental conditions

Spontaneous unit activity and changes in its statistical parameters during electrical stimulation of the palms at 25 or 50/min were studied in four monkeys under chronic experimental conditions. Altogether 337 recordings of the activity of 64 neurons for durations of 2 and 3 min were studied. The mean firing rate was relatively low (5.7 spikes/sec). As a rule the unit activity remained stable for several tens of minutes. It could change spontaneously to new patterns and again remain stationary. These transitions took place during recording of spontaneous activity and also during stimulation of the animal, but they were independent of it. Interspike interval histograms were varied and most were polymodal. Their pattern changed with changes in the firing rate of the neurons. The position of the modes along the time axis and the type of distribution were the most conservative characteristics of the histograms. The probability of appearance of intervals was highest at 30, 60, 90, and 210–240 msec. The presence of stable intervals with increased probability of appearance may be the result of the existence of chains of neurons in the caudate nucleus with fixed temporal parameters.     

Reduced light response of neuronal firing activity in the suprachiasmatic nucleus and optic nerve of cryptochrome-deficient mice

To examine roles of the Cryptochromes (Cry1 and Cry2) in mammalian circadian photoreception, we recorded single-unit neuronal firing activity in the suprachiasmatic nucleus (SCN), a primary circadian oscillator, and optic nerve fibers in vivo after retinal illumination in anesthetized Cry1 and Cry2 double-knockout (Cry-deficient) mice. In wild-type mice, most SCN neurons increased their firing frequency in response to retinal illumination at night, whereas only 17% of SCN neurons responded during the daytime. However, 40% of SCN neurons responded to light during the daytime, and 31% of SCN neurons responded at night in Cry-deficient mice. The magnitude of the photic response in SCN neurons at night was significantly lower (1.3-fold of spontaneous firing) in Cry-deficient mice than in wild-type mice (4.0-fold of spontaneous firing). In the optic nerve near the SCN, no difference in the proportion of light-responsive fibers was observed between daytime and nighttime in both genotypes. However, the response magnitude in the light-activated fibers (ON fibers) was high during the nighttime and low during the daytime in wild-type mice, whereas this day-night difference was not observed in Cry-deficient mice. In addition, we observed day-night differences in the spontaneous firing rates in the SCN in both genotypes and in the fibers of wild-type, but not Cry-deficient mice. We conclude that the low photo response in the SCN of Cry-deficient mice is caused by a circadian gating defect in the retina, suggesting that Cryptochromes are required for appropriate temporal photoreception in mammals.     

Characteristics of background unit activity in the nucleus reticularis of the human thalamus

Background firing activity was examined in 240 neurons belonging to the thalamic nucleus reticularis (Rt) in the unanesthetized human brain by extracellular microelectrode recording techniques during stereotaxic surgery for dyskinesia. The cellular organization of Rt was shown to be nonuniform, and distinguished by the presence of three types of neuron: one with arrhythmic single discharge (A-type, 40%), another with rhythmic (2–5 Hz) generation of short high-frequency (of up to 500/sec) burster discharges (B-type, 49%) and a third with aperiodic protracted high-frequency (of up to 500/sec) bursting discharges separated by "silent" intervals of a constant duration of 80–150 msec (i.e., C-type, 11%). Differences between the background activity pattern of these cell types during loss of consciousness under anesthesia are described. Tonic regulation of neuronal type was not pronounced but a tendency was noticed in the cells towards a consistent rise in firing rate, rhythmic frequency and variability, etc. in both A and B units, especially in the latter. Findings pointing to the absence of a direct relationship between rhythmic activity in the Rt and parkinsonian tremor were confirmed. Background activity in B-type cells was found to increase and then stabilize with a rise in the degree of tremor. The nature of regular bursting activity patterns in B and C neurons is discussed in the light of our findings.Institute of Chemical Physics, Academy of Sciences of the USSR, Moscow. Institute of Neurosurgery, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 19, No. 4, pp. 456–466, July–August, 1987.