What is neuronal activity

Article Google Scholar. Chrobak, J. High-frequency oscillations in the output networks of the hippocampal—entorhinal axis of the freely-behaving rat. Engel, A. Why does the cortex oscillate? Singer, W. Visual feature integration and the temporal correlation hypothesis. Usrey, W. Synchronous activity in the nervous system. CAS Google Scholar. Shadlen, M. Synchrony unbound: a critical evaluation of the temporal binding hypothesis. Neuron 24 , 67—77 Gray, C. The temporal correlation hypothesis of visual feature integration: still alive and well.

Neuron 24 , 31—47 Aertsen, A. Response synchronization in the visual cortex. Wehr, M. Relationship between afferent and central temporal patterns in the locust olfactory system. Laurent, G. Odor encoding as an active, dynamical process: experiments, computation, and theory. Bazhenov, M. Model of transient oscillatory synchronization in the locust antennal lobe. Neuron 30 , — MacLeod, K. Who reads temporal information contained across synchronized and oscillatory spike trains? Nature , — This and the next paper are complementary studies on the functional role of synchrony in the olfactory system of insects.

When neurons in the antennal lobe are artificially desynchronized, the responses of downstream neurons are markedly distorted and the animals' ability to discriminate odours is impaired. Similar experiments investigating the impact of oscillations on neural circuits and on behaviour should, at some point, be possible in mammals.

Stopfer, M. Impaired odour discrimination on desynchronization of odour-encoding neural assemblies. Nature , 70—74 Kashiwadani, H. Dan, Y. Coding of visual information by precisely correlated spikes in the lateral geniculate nucleus.

Nature Neurosci. DeCharms, R. Primary cortical representation of sounds by the coordination of action potential timing. Kreiter, A. Stimulus-dependent synchronization of neuronal responses in the visual cortex of the awake macaque monkey. Perkel, D. Neuronal spike trains and stochastic point processes. Simultaneous spike trains. Dynamics of neuronal firing correlation: modulation of 'effective connectivity'. Brody, C. Correlations without synchrony. Neural Comput.

Points out several ways in which peaks might arise in cross-correlation histograms. An important reference for anyone using this method. Vaadia, E. Dynamics of neuronal interactions in monkey cortex in relation to behavioural events.

Ts'o, D. Relationships between horizontal interactions and functional architecture in cat striate cortex as revealed by cross-correlation analysis. Gochin, P. Functional interactions among neurons in inferior temporal cortex of the awake macaque. Nelson, J. Spatial and temporal coherence in cortico—cortical connections: a cross-correlation study in areas 17 and 18 in the cat.

Brosch, M. Correlations between neural discharges are related to receptive field properties in cat primary auditory cortex. Livingstone, M. Oscillatory firing and interneuronal correlations in squirrel monkey striate cortex. Stimulus-dependent neuronal oscillations and local synchronization in striate cortex of the alert cat.

Murthy, V. Oscillatory activity in sensorimotor cortex of awake monkeys: synchronization of local field potentials and relation to behavior. Synchronization of neurons during local field potential oscillations in sensorimotor cortex of awake monkeys. Donoghue, J. Neural discharge and local field potential oscillations in primate motor cortex during voluntary movements. Abeles, M. Role of the cortical neuron: integrator or coincidence detector? Softky, W. Sub-millisecond coincidence detection in active dendritic trees.

Neuroscience 58 , 13—41 The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs. Integrator or coincidence detector? The role of the cortical neuron revisited.

Trends Neurosci. Carr, C. A circuit for detection of interaural time differences in the brain stem of the barn owl. Agmon-Snir, H. The role of dendrites in auditory coincidence detection Science , — Mel, B.

Synaptic integration in an excitable dendritic tree. Margulis, M. Temporal integration can readily switch between sublinear and supralinear summation. Press, Oxford, Poirazi, P. Impact of active dendrites and structural plasticity on the memory capacity of neural tissue. Neuron 29 , — Archie, K. Structural plasticity, dendritic subunits, and the development of nonlinear visual receptive field properties. Azouz, R. Dynamic spike threshold reveals a mechanism for synaptic coincidence detection in cortical neurons in vivo.

Natl Acad. USA 97 , — Burkitt, A. Analysis of integrate-and-fire neurons: synchronization of synaptic input and spike output. Diesmann, M. Stable propagation of synchronous spiking in cortical neural networks. A different perspective on coincidence detection and synchrony.

A network of neurons is activated by a volley of input spikes that occurs at a certain time and with a given temporal width. The response is another volley of spikes, the timing and width of which depend on network parameters.

Analytical and simulation results show that such volleys can propagate stably and with minimal time jitter through multiple layers. Noise, neural codes and cortical organization. The variable discharge of cortical neurons: implications for connectivity, computation and information coding. The effects of synchronized inputs at the single neuron level.

Effects of input synchrony on the firing rate of a three-conductance cortical neuron model. Salinas, E. Impact of correlated synaptic input on output firing rate and variability in simple neuronal models. Using theoretical models and computer simulations, the authors study the possible effects of input correlations on a postsynaptic neuron, as well as the properties that make the postsynaptic neuron more or less sensitive to them.

A key condition for high sensitivity is the balance between excitation and inhibition; a balanced neuron might be strongly affected by small changes in input synchrony or by oscillations in input firing rates.

Bell, A. California at San Diego, California Troyer, T. Physiological gain leads to high ISI variability in a simple model of a cortical regular spiking cell.

Feng, J. Impact of correlated inputs on the output of the integrate-and-fire model. Tsodyks, M. Rapid state switching in balanced cortical network models. Network 6 , — Van Vreeswijk, C. Chaos in neuronal networks with balanced excitatory and inhibitory activity. Science , — Chaotic balanced state in a model of cortical circuits.

Brunel, N. Fast global oscillations in networks of integrate-and-fire neurons with low firing rates. Plotting the spike burst integral as a function of the ventricular O 2 concentration red circles and red dashed line in Fig. In contrast, the integral of the O 2 transient increased with higher ventricular O 2 levels green circles and green dashed line in Fig. Normalization of the integral of the O 2 transient with respect to the corresponding spike burst integral yielded the O 2 -consumption rate Fig.

Thus, the enhanced availability of O 2 obviously dominates the increase of O 2 consumption during spike bursts even though reacquisition of the baseline level occurs faster under these circumstances. O 2 concentrations in the brain of isolated preparations of Xenopus tadpoles were close to zero in the IV th ventricle and adjacent hindbrain in air-saturated bath solutions. Application of KCN or fixation with EtOH raised ventricular O 2 concentrations to bath levels, indicating complete consumption of available O 2 prior to the metabolic inactivation.

Inhibition of spike activity and spontaneous bursts caused a reversible decrease and transient increase of the O 2 consumption, respectively. Direct in vivo measurements of O 2 concentrations within specific compartments of the brain are usually very difficult if not impossible to obtain, mostly due to the virtual inaccessibility of the structure, the difficult targeted placement of O 2 electrodes, the tedious maintenance of constant vital parameters of the animal, and the inability to alter O 2 concentrations or neuronal activity in an experimentally controlled fashion.

In vitro whole brain or head preparations of various vertebrate species with intact sensory organs, motor effectors, and central nervous circuits [ 27 ], which can be maintained for several days after isolation in ionically defined Ringer solutions, are highly suitable alternatives for in vivo measurements. The maintenance of isolated whole head preparations of Xenopus laevis tadpoles in Ringer solution [ 27 ] allows a controlled supply of O 2 but also of other metabolically relevant molecules such as lactate or glucose through the temperature-, pH-, and O 2 -controlled surrounding bath medium.

The bath chamber furthermore allows an easy and fast exchange of solutions and thereby application of blockers that impair metabolic e. The plain visibility and accessibility of the central nervous system and its ventricular compartments in isolated preparations of Xenopus tadpoles Fig.

Moreover, the vitality and functionality of isolated amphibian brains or whole heads [ 27 ] allows monitoring in vivo-like behaviors by an in vitro approach. Motor behaviors such as tail-based swimming or eye movements [ 42 ] can be evoked by close-to-natural stimuli. The causal link between spontaneous extraocular motor spike bursts and subsequent increase in O 2 consumption Figs. Comparable correlations between spike activity and O 2 tissue concentration [ 9 , 10 , 12 ] or turnover of energy equivalents [ 8 , 14 , 43 ] have been established for various neuronal populations in slice preparations.

However, the latter, more reductionistic model system prevents assigning O 2 consumption to the production of behaviorally relevant neuronal transformations or production of motor commands or behaviors. In a next step, superior oblique motoneurons will be activated by visuo-vestibular stimulation sensory activation or galvanic currents to elucidate the O 2 dynamics during natural activation of optokinetic and vestibulo-ocular reflexes in isolated tadpole preparations.

The knowledge obtained by our study now allows framing the experimental conditions such that it will be possible to visualize the O 2 consumption dynamics during a particular motor behavior.

The amount of O 2 consumed by an isolated preparation became immanent through the vertical profile of the O 2 concentration above the head in the bath solution Fig. The reduced O 2 level signifies the sustained consumption by the viable tissue that is obviously faster than the resupply via diffusion from the bath, which is particularly obvious in the brain where the IV th ventricle and adjacent hindbrain is virtually anoxic blue in Fig.

Accordingly, the O 2 consumption due to the metabolic activity generates a sink with a gradient perpendicular to the tissue surface that varies in slope with the bath O 2 level Fig. Inactivation of the tissue with EtOH Fig. Independent of the bath level, the O 2 concentration in the IV th ventricle and adjacent hindbrain were identical compare black and blue circles in Fig. Moreover, increases of bath O 2 levels caused concurrent alterations of the respective concentration in both compartments with similar dynamics and magnitude.

This indicates that neither the surface nor cellular elements form a major barrier for O 2 diffusion into the brain. Thus, O 2 monitoring in the ventricular compartment directly reflects the O 2 dynamics of the adjacent hindbrain tissue and has the advantage of not damaging the neuronal tissue.

In air-saturated bath solutions, the O 2 concentration in the ventricle and adjacent brain tissue was close to zero Figs. Similar low O 2 levels were also observed in studies that employed mammalian slice preparations in air-saturated Ringer solutions [ 8 , 26 ]. The virtual absence of O 2 in isolated amphibian brains or mammalian brains in vivo [ 44 , 45 ] is likely due to the efficient metabolic turnover of all available O 2 to generate ATP.

Utilization of O 2 by this pathway complies with the equalization of ventricular and bath O 2 levels following the application of KCN, known to block mitochondrial activity. This identifies oxidative phosphorylation as the dominating if not exclusive O 2 -consuming process in the amphibian brain in compliance with the general importance of this metabolic pathway e. This allows testing the influence of O 2 on the generation of ATP and neuronal computations over a relatively wide range.

While the substantial O 2 consumption by brain tissue is well known, it is less clear, which cellular elements dominate the O 2 turnover and how this is governed by the biophysical and morphological characteristics of the neuronal types involved. A number of studies, mostly on slice preparations, have demonstrated the necessity of adequate O 2 levels for sustained neuronal activity and synaptic transmission [ 5 , 12 ].

Other studies emphasize the need for considerable amounts of O 2 to maintain neuron-specific resting membrane potential levels [ 24 ] and for the homeostasis of non-neuronal elements such as astrocytes [ 47 , 48 ]. The most parsimonious explanation is that the homeostasis related to spike generation and repolarization at least in the isolated amphibian brain under in vitro conditions consumes about half of the available O 2 in air-saturated bath solutions.

Moreover, the recovery of the superior oblique nerve spike discharge after an abolishment of action potentials by MS was linearly correlated with the O 2 consumption in all cases Fig. However, the apparent lack of coherence of spike rates in different superior oblique nerves with respect to O 2 consumption color-coded dots in Fig. Even though the superior oblique nerve discharge is only a proxy for central nervous spike activity, these measurements clearly infer causality and allow quantitative correlations between spike rate and O 2 consumption.

The somewhat dissociated correlation between ventricular O 2 concentration and firing rate recovery during the first phase of MS washout is potentially related to the block of ion channels, although with varying sensitivity, in addition to those that contribute to the action potential generation [ 40 , 49 ]. Blocking these channels might for instance affect the membrane potential and, thereby, reduce the energy and thus O 2 consumption for the maintenance of the resting membrane potential.

This therefore requires a more differentiated and extended view on the link between spike discharge, resting membrane potential, and O 2 consumption. It is well known from mammalian systems that the maintenance of the resting membrane potential, non-signaling processes, and cellular housekeeping e.

As an example, O 2 consumption in mouse hippocampal slices was still substantial during tetrodotoxin-blocked action potentials [ 10 ]. A further contribution to O 2 consumption during MSblocked neuronal signaling might be attributed to O 2 diffusion into neighboring areas, where blockage of neural firing might be incomplete, which, however, was not determined in the current study. The amount of O 2 to sustain neuronal spike discharge at rest increased further during spontaneous spike burst activity of the superior oblique nerve Figs.

The discharge of this extraocular motor nerve is an excellent proxy for correlating increased neuronal activity with the O 2 level measured within the IV th ventricle because the major presynaptic cellular generators of these spike bursts are located in the spatially adjacent hindbrain vestibular nuclei and the superior oblique motor nucleus below the floor of the IV th ventricle [ 39 ]. While the transient increase in O 2 consumption is rather small in air-saturated bath solutions, due to the very low ventricular O 2 levels, it becomes more pronounced at higher bath O 2 concentrations.

These larger O 2 transients, however, are not due to an increase in spike burst magnitude but likely reflect an augmentation in the fractional contribution of oxidative phosphorylation to ATP production compared to other pathways such as glycolysis Fig. However, this delay is slower compared to respective values reported in other, although mammalian, in vitro studies [ 8 , 9 ] and potentially derives from the spatial dissociation of the measurement of the burst-relevant neuronal activity in the hindbrain and of O 2 in the ventricle.

The quantifiable correlation between spike activity and O 2 consumption in the current study represents an ideal condition to further evaluate the link between computational capability and metabolic activity in behaviorally relevant and morpho-physiologically characterized neural circuits.

Isolated preparations such as employed here provide the accessibility to such networks for physiological recordings and calcium imaging while simultaneously offering the advantage to manipulate and measure O 2 concentrations. Therefore, this study, using a novel model system, is only a first step in the attempt to better understand how metabolic requirements and constraints affect neuronal function.

Future experiments using this model system will exploit the accessibility of successive developmental stages of Xenopus to probe alterations in the O 2 turnover in the hindbrain during ontogeny and further elucidate the energetic demands and costs of activating basic motor behaviors.

The virtual in vivo-like experimental conditions despite isolation of the tissue and loss of vascular oxygen supply allows direct probing of the O 2 consumption of cell populations involved in specific behaviorally relevant neuronal computations. This includes evaluation of the influence of parameters such as temperature, ionic composition of the extracellular medium, availability, and type of metabolic substrates or the relation between O 2 availability and neuronal function.

Finally, isolated Xenopus preparations allow exploring the capacity of photosynthetic algae [ 51 ], experimentally introduced into the brain prior to the isolation, to produce O 2 upon illumination, which thereby supplies or even enhances the O 2 level in the tissue. Given the in vivo-like experimental conditions, it is probable that a similar value would be obtained in the living animal. Bath application of a local anesthetic completely abolished spike activity and thereby revealed that half of the O 2 consumption supplies neuronal activity.

The possibility to measure at the same time O 2 consumption and neuronal activity in an in vivo-like brain preparation under physiological conditions now allows to directly interfere with various aspects of the coupling between brain metabolism and neuronal computations. Tadpoles were anesthetized in 0. The skin on the dorsal part of the head was partially removed, the skull opened, the forebrain disconnected, both optic nerves severed, and the choroid plexus above the IV th ventricle removed [ 31 ].

The remaining central nervous system, inner ears, and eyes with extraocular muscles and respective motoneuronal innervation were functionally preserved [ 27 ]. In parts of the experiments, extraocular motor spike discharge was recorded from the trochlear nerve after disconnection from the superior oblique target muscle at the innervation site.

For all experiments, isolated preparations Fig. The O 2 electrode was positioned and advanced with a piezo-stepper attached to a micromanipulator both from Sensapex, Finland. Spontaneous multi-unit spike discharge of the superior oblique motor nerve was recorded extracellularly EXT F; npi electronics; Tamm, Germany with glass suction electrodes [ 37 ]. The neuronal activity of the isolated preparation, detected as spontaneous multi-unit spike discharge of the superior oblique motor nerve as a proxy, was blocked by bath-application of MS 0.

Discharge rates of the superior oblique motor nerve were obtained from multi-unit spike activity using Spike2 Cambridge Electronic Design, UK scripts. Spike rates were obtained from the spike times in a given recording by counting all events above a pre-determined amplitude threshold.

The burst integral was determined as area under the curve following subtraction of the resting rate from the onset of the spike burst until the time when the spike burst reached again baseline level. The O 2 concentration in the IV th ventricle or brain and the bath chamber were measured with the technical approach and sensors described above.

The integral of the O 2 consumption during spike burst activity was determined as area between the baseline and the peak O 2 consumption starting at the onset of the change in O 2 level and the time when the O 2 level reached again baseline.

Integrals of spike burst-related O 2 consumption at different bath O 2 concentrations were determined with respect to the actual bath O 2 level during a particular experimental condition. Plotting and calculation of linear regressions was performed in Microcal Origin 6. Statistical differences between experimental groups were calculated with the non-parametric Mann-Whitney U test unpaired parameters; Prism, Graphpad Software, Inc.

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