Ionic and neuromodulatory regulation of burst discharge controls frequency tuning

Sensory neurons encode natural stimuli by changes in firing rate or by generating specific firing patterns, such as bursts. Many neural computations rely on the fact that neurons can be tuned to specific stimulus frequencies. It is thus important to understand the mechanisms underlying frequency tuning. In the electrosensory system of the weakly electric fish, Apteronotus leptorhynchus, the primary processing of behaviourally relevant sensory signals occurs in pyramidal neurons of the electrosensory lateral line lobe (ELL). These cells encode low frequency prey stimuli with bursts of spikes and high frequency communication signals with single spikes. We describe here how bursting in pyramidal neurons can be regulated by intrinsic conductances in a cell subtype specific fashion across the sensory maps found within the ELL, thereby regulating their frequency tuning. Further, the neuromodulatory regulation of such conductances within individual cells and the consequences to frequency tuning are highlighted. Such alterations in the tuning of the pyramidal neurons may allow weakly electric fish to preferentially select for certain stimuli under various behaviourally relevant circumstances.     

Burst control: Synaptic conditions for burst generation in cortical layer 5 pyramidal neurons

The output of neocortical layer 5 pyramidal cells (L5PCs) is expressed by a train of single spikes with intermittent bursts of multiple spikes at high frequencies. The bursts are the result of nonlinear dendritic properties, including Na⁺, Ca²⁺, and NMDA spikes, that interact with the ~10,000 synapses impinging on the neuron’s dendrites. Output spike bursts are thought to implement key dendritic computations, such as coincidence detection of bottom-up inputs (arriving mostly at the basal tree) and top-down inputs (arriving mostly at the apical tree). In this study we used a detailed nonlinear model of L5PC receiving excitatory and inhibitory synaptic inputs to explore the conditions for generating bursts and for modulating their properties. We established the excitatory input conditions on the basal versus the apical tree that favor burst and show that there are two distinct types of bursts. Bursts consisting of 3 or more spikes firing at < 200 Hz, which are generated by stronger excitatory input to the basal versus the apical tree, and bursts of ~2-spikes at ~250 Hz, generated by prominent apical tuft excitation. Localized and well-timed dendritic inhibition on the apical tree differentially modulates Na⁺, Ca²⁺, and NMDA spikes and, consequently, finely controls the burst output. Finally, we explored the implications of different burst classes and respective dendritic inhibition for regulating synaptic plasticity.     

Complex evolution of spike patterns during burst propagation through feed-forward networks

Stable signal transmission is crucial for information processing by the brain. Synfire-chains, defined as feed-forward networks of spiking neurons, are a well-studied class of circuit structure that can propagate a packet of single spikes while maintaining a fixed packet profile. Here, we studied the stable propagation of spike bursts, rather than single spike activities, in a feed-forward network of a general class of excitable bursting neurons. In contrast to single spikes, bursts can propagate stably without converging to any fixed profiles. Spike timings of bursts continue to change cyclically or irregularly during propagation depending on intrinsic properties of the neurons and the coupling strength of the network. To find the conditions under which bursts lose fixed profiles, we propose an analysis based on timing shifts of burst spikes similar to the phase response analysis of limit-cycle oscillators.     

Triggering and gating of motor responses by sensory stimulation: behavioural selection in Xenopus embryos.

Neural mechanisms underlying selection of motor responses are largely unknown in vertebrates. This study shows that in immobilized Xenopus embryos, brief mechanical or electrical stimulation of the trunk skin can trigger sustained fictive swimming, whereas sustained pressure or repetitive electrical stimulation can evoke fictive struggling. These two rhythmic motor patterns are distinct: alternating single motor root spikes propagate from head to tail during swimming; alternating motor root bursts propagate from tail to head during struggling. As both motor patterns can be evoked in embryos with the CNS transected caudal to the cranial roots, the sensory pathway responsible must have direct access to the spinal cord. Rohon-Beard sensory neurons provide the only such pathway known. They respond appropriately to brief stimuli applied to the trunk skin, and also to repetitive electrical stimuli and sustained pressure. The results suggest that Rohon-Beard sensory neurons can both trigger sustained swimming and 'gate in' struggling motor patterns, and thus effect behavioural selection according to their pattern of activity.     

Distinct neuronal coding schemes in memory revealed by selective erasure of fast synchronous synaptic transmission

Neurons encode information by firing spikes in isolation or bursts and propagate information by spike-triggered neurotransmitter release that initiates synaptic transmission. Isolated spikes trigger neurotransmitter release unreliably but with high temporal precision. In contrast, bursts of spikes trigger neurotransmission reliably (i.e., boost transmission fidelity), but the resulting synaptic responses are temporally imprecise. However, the relative physiological importance of different spike-firing modes remains unclear. Here, we show that knockdown of synaptotagmin-1, the major Ca(2+) sensor for neurotransmitter release, abrogated neurotransmission evoked by isolated spikes but only delayed, without abolishing, neurotransmission evoked by bursts of spikes. Nevertheless, knockdown of synaptotagmin-1 in the hippocampal CA1 region did not impede acquisition of recent contextual fear memories, although it did impair the precision of such memories. In contrast, knockdown of synaptotagmin-1 in the prefrontal cortex impaired all remote fear memories. These results indicate that different brain circuits and types of memory employ distinct spike-coding schemes to encode and transmit information.     

Temporal interaction between single spikes and complex spike bursts in hippocampal pyramidal cells

Cortical pyramidal cells fire single spikes and complex spike bursts. However, neither the conditions necessary for triggering complex spikes, nor their computational function are well understood. CA1 pyramidal cell burst activity was examined in behaving rats. The fraction of bursts was not reliably higher in place field centers, but rather in places where discharge frequency was 6-7 Hz. Burst probability was lower and bursts were shorter after recent spiking activity than after prolonged periods of silence (100 ms-1 s). Burst initiation probability and burst length were correlated with extracellular spike amplitude and with intracellular action potential rising slope. We suggest that bursts may function as "conditional synchrony detectors," signaling strong afferent synchrony after neuronal silence, and that single spikes triggered by a weak input may suppress bursts evoked by a subsequent strong input.     

Neurophysiology of Ganglia of Auerbach's Plexus

The enteric plexuses of the automatic nervous system may beconsidered, on the basis of both function and morphology, tobe a simple integrative nervous system of vertebrate animals.Microelectrcde studies of single unit activity within entericganglia reveal four distinct types of ganglion cells distinguishedon the basis of pattern of spike discharge. These are (i) burst-typeunits which spontaneously discharge bursts of spikes at periodicintervals; (ii) fast- and slowly-adapting mechanoreceptors;(iii) tonic-type units which respond to mechanical stimulationwith prolonged, all-or-nothing trains of spikes; (iv) single-spikeunits which spontaneously discharge single action potentialsat variable intervals. The enteric plexuses are adapted forcontrol of the intestinal musculature which behaves as an electricalsyncytium activated by myogenic pacemaker potentials. The mechanismof neural control is integration of continuous neurogenic inhibitionof the inherently excitable musculature.     

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.     

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.     

Rhythmic TMS over parietal cortex links distinct brain frequencies to global versus local visual processing

Neural networks underlying visual perception exhibit oscillations at different frequencies (e.g.,). But how these map onto distinct aspects of visual perception remains elusive. Recent electroencephalography data indicate that theta or beta frequencies at parietal sensors increase in amplitude when conscious perception is dominated by global or local features, respectively, of a reversible visual stimulus. But this provides only correlative, noninterventional evidence. Here we show via transcranial magnetic stimulation (TMS) interventions that short rhythmic bursts of right-parietal TMS at theta or beta frequency can causally benefit processing of global or local levels, respectively, for hierarchical visual stimuli, especially in the context of salient incongruent distractors. This double dissociation between theta and beta TMS reveals distinct causal roles for particular frequencies in processing global versus local visual features.     

Encoding of Time-varying Stimuli in Populations of Cultured Neurons

We wondered whether random populations of dissociated cultured cortical neurons, despite of their lack of structure and/or regional specialization, are capable of modulating their neural activity as the effect of a time-varying stimulation – a simulated ‘sensory’ afference. More specifically, we used localized low-frequency, non-periodic trains of stimuli to simulate sensory afferences, and asked how much information about the original trains of stimuli could be extracted from the neural activity recorded at the different sites. Furthermore, motivated by the results of studies performed both in vivo and in vitro on different preparations, which suggested that isolated spikes and bursts may play different roles in coding time-varying signals, we explored the amount of such ‘sensory’ information that could be associated to these different firing modes. Finally, we asked whether and how such ‘sensory’ information is transferred from the sites of stimulation (i.e., the ‘sensory’ areas), to the other regions of the neural populations. To do this we applied stimulus reconstruction techniques and information theoretic concepts that are typically used to investigate neural coding in sensory systems. Our main results are that (1) slow variations of the rate of stimulation are coded into isolated spikes and in the time of occurrence of bursts (but not in the bursts’ temporal structure); (2) increasing the rate of stimulation has the effect of increasing the proportion of isolated spikes in the average evoked response and their importance in coding for the stimuli; and, (3) the ability to recover the time course of the pattern of stimulation is strongly related to the degree of functional connectivity between stimulation and recording sites. These observations parallel similar findings in intact nervous systems regarding the complementary roles of bursts and tonic spikes in encoding sensory information. Our results also have interesting implications in the field of neuro-robotic interfaces. In fact, the ability of populations of neurons to code information is a prerequisite for obtaining hybrid systems, in which neuronal populations are used to control external devices.     

The sensory functions of the cerebellum of the thornback ray,Platyrhinoidis triseriata

Summary Single unit spikes and evoked field potentials were recorded in different parts and depths of the corpus cerebelli and auricle of immobilized rays before and after stimulating with light, electric fields, touch, tail bending and direct shock to mechanoreceptive nerves of the lateral line.Discrete areas of the cerebellum are responsive to these modalities and the areas show limited overlap; they are all distinct from the area reported by Plassmann to be responsive to angular acceleration. The visual and tactile-proprioceptive areas are large; the electric area is small. Most units are excited only by one modality.The tail is represented only in the posterior lobe; trigeminal innervation extends from the posterior onto the anterior lobe, suggesting some topographic projection.The dynamic characteristics of the responses were examined particulary in the visual units. To a flash, units discharge up to six bursts of spikes in 500 ms. This pattern is reduced at repetition rates > 1/s; above ca. 4/s units tend to fire irregularly. Various kinds of units are found in respect to the succession of responses to short trains of flashes. Some units fire much better to objects moving in a limited visual field with a certain direction and rate.Abbreviation EP evoked potential     

Neural coding of natural stimuli: information at sub-millisecond resolution

Sensory information about the outside world is encoded by neurons in sequences of discrete, identical pulses termed action potentials or spikes. There is persistent controversy about the extent to which the precise timing of these spikes is relevant to the function of the brain. We revisit this issue, using the motion-sensitive neurons of the fly visual system as a test case. Our experimental methods allow us to deliver more nearly natural visual stimuli, comparable to those which flies encounter in free, acrobatic flight. New mathematical methods allow us to draw more reliable conclusions about the information content of neural responses even when the set of possible responses is very large. We find that significant amounts of visual information are represented by details of the spike train at millisecond and sub-millisecond precision, even though the sensory input has a correlation time of ~55 ms; different patterns of spike timing represent distinct motion trajectories, and the absolute timing of spikes points to particular features of these trajectories with high precision. Finally, the efficiency of our entropy estimator makes it possible to uncover features of neural coding relevant for natural visual stimuli: first, the system's information transmission rate varies with natural fluctuations in light intensity, resulting from varying cloud cover, such that marginal increases in information rate thus occur even when the individual photoreceptors are counting on the order of one million photons per second. Secondly, we see that the system exploits the relatively slow dynamics of the stimulus to remove coding redundancy and so generate a more efficient neural code.     

Pattern and correlation of fast and slow spontaneous unit activity in the visual cortex

Spontaneous unit activity in the visual cortex and its changes during stimulation by continuous light or flashes were investigated in waking rabbits. The study of distributions of adjacent intervals showed that the neurons differ in the ratio of burst (fast, with intervals of up to 15–40 msec) and nonburst (slow) activity and in the character of changes from one type of activity to the other. Of the total number of spikes 63% were outside bursts; the ratio of their number to the number of spikes within bursts consisting of two or of three or more spikes was 27:3:1. The relative stability of the burst structure of spontaneous activity and the limited number of spikes in them (on average 2.4) were demonstrated. Bursts of three or more spikes (mean 3.6) were irregular, and in 79% of them a longer interval (18.6±2.4 msec) was observed before the shortest interval (7.9±0.9 msec). Bursts of spikes of most neurons during photic stimulation contain more spikes with shorter intervals; they also began more frequently with the shortest interval, possibly signifying an increase in the steepness and amplitude of the EPSPs lying at their basis. However, in 20% of neurons spontaneous bursts included more spikes and with shorter intervals than bursts evoked by flash stimulation.Research Institute of Psychiatry, Ministry of Health of the RSFSR, Moscow. Translated from Neirofiziologiya, Vol. 11, No. 4, pp. 311–320, July–August, 1979.     

Electrophysiology of "yellow cells," neurosecretory neurones in Lymnaea.

The thirty Yellow Cells of Lymnaea show single, double and other extra spike modes of firing. Yellow Cell bursts consist of various combinations of single, doublet and triplet spikes whose number per burst varies spontaneously. Single spike firing modes of activity can be converted into doublets or bursts (and vice versa) by applying steady currents of the appropriate polarity. Spike activity is basically endogenous although it is modulated by low frequency synaptic input originating from within the brain. Interburst interval is affected by the number of spikes occurring in the preceding burst. This varies spontaneously or can be induced by applying appropriately timed current pulses or occurs following synaptic input. Excitatory synaptic input often induces bursts which far exceed the duration of the input and which are followed by long periods of inhibition.     

Efficient inhibition of bursts by bursts in the auditory system of crickets

In crickets, auditory information about ultrasound is carried bilaterally to the brain by the AN2 neurons. The ON1 neuron provides contralateral inhibitory input to AN2, thereby enhancing bilateral contrast between the left and right AN2s, an important cue for sound localization. We examine how the structures of the spike trains of these neurons affect this inhibitory interaction. As previously shown for AN2, ON1 responds to salient peaks in stimulus amplitude with bursts of spikes. Spike bursts, but not isolated spikes, reliably signal the occurrence of specific features of the stimulus. ON1 and AN2 burst at similar times relative to the amplitude envelope of the stimulus, and bursts are more tightly time-locked to stimulus feature than the isolated spikes. As a consequence, spikes that, in the absence of contralateral inhibition, would occur within AN2 bursts are more likely to be preceded by spikes in ON1 (mainly also in bursts) than are isolated AN2 spikes. This leads to a large decrease in the burst rate of the inhibited AN2. We conclude that the match in coding properties of ON1 and AN2 allows contralateral inhibition to be most efficient for those portions of the response that carry the behaviourally relevant information, i.e. for bursts. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Time coding in the midbrain of mormyrid electric fish. II. Stimulus selectivity in the nucleus exterolateralis pars posterior

The anterior and posterior exterolateral nuclei (ELa and ELp) of the mormyrid midbrain are thought to play a critical role in the temporal analysis of the electric discharge waveforms of other individuals. The peripheral electroreceptors receiving electric organ discharges (EODs) of other fish project through the brainstem to ELa via a rapid conducting pathway. EODs, composed of brief, but stereotyped waveforms are encoded as a temporal pattern of spikes. From previous work, we know that phase locking is precise in ELa. Here it is shown that evoked potentials recorded from ELp show a similar high degree of phase locking, although the evoked potentials last much longer. Single-unit recordings in ELp reveal two distinct populations of neurons in ELp: type I cells are responsive to voltage step functions, and not tuned for stimulus duration; type II cells are tuned to a specific range of stimulus durations. Type II cells are less responsive than type I cells, tend to respond with bursts of action potentials rather than with single spikes, have a longer latency, show weaker time locking to stimuli, and are more sensitive to stimulus polarity and amplitude. The stimulus selectivity of type II cells may arise from convergence of type I cell inputs. Despite the loss of rapid conduction between ELa and ELp, analysis of temporal features of waveforms evidently continues in ELp, perhaps through a system of labeled lines. Accepted: 25 June 1997     

How noise and coupling induce bursting action potentials in pancreatic {beta}-cells

Unlike isolated beta-cells, which usually produce continuous spikes or fast and irregular bursts, electrically coupled beta-cells are apt to exhibit robust bursting action potentials. We consider the noise induced by thermal fluctuations as well as that by channel-gating stochasticity and examine its effects on the action potential behavior of the beta-cell model. It is observed numerically that such noise in general helps single cells to produce a variety of electrical activities. In addition, we also probe coupling via gap junctions between neighboring cells, with heterogeneity induced by noise, to find that it enhances regular bursts.