Information processing by nonspiking interneurons: passive and active properties of dendritic membrane determine synaptic integration

Nonspiking interneurons control activities of postsynaptic cells without generating action potentials in the central nervous system of many invertebrates. Physiological characteristics of their dendritic membrane have been analyzed in previous studies using single electrode current- and voltage-clamp techniques. We constructed a single compartment model of an identified nonspiking interneuron of crayfish. Experimental results allowed us to simulate how the passive and active properties of the dendritic membrane influence the integrative processing of synaptic inputs. The results showed that not only the peak amplitude but also the time course of synaptic potentials were dependent on the membrane potential level at which the synaptic activity was evoked. When the synaptic input came sequentially, each individual input was still discernible at depolarized levels at which the membrane time constant was short due to depolarization-dependent membrane conductances. In contrast, synaptic potentials merged with each other to develop a sustained potential at hyperpolarized levels where the membrane behaved passively. Thus, synaptic integration in a single nonspiking interneuron depends on the value of membrane potential at which it occurs. This probably reflects the temporal resolution required for specific types of information processing.     

The relationship between flash evoked potentials and evoked amplitude modulation patterns of an applied UHF electromagnetic field in the rat

Pilot studies demonstrate evidence that the electrophysiological processes associated with flash stimulation of the central nervous system (CNS) of rats, as seen in the recordings of visual-evoked potentials, may also be detectable using an ultrahigh frequency electromagnetic field (UHFEMF). Patterns of amplitude modulation of an applied UHFEMF, when recorded and averaged, show strong correlations with simultaneously recorded evoked potentials. The data support the hypothesis that the UHFEMF amplitude is altered in a dynamic fashion by the tissue's electrophysiological processes that are involved with the generation of CNS electric fields.     

Effects of death of a single neuron on the functional organization of the neuronal ensemble in the leech

The reaction of leech nervous system after elimination of individual mechanosensory neuron by intracellular Pronase injection were studied. In the motor neurons connected with killed cells at 14-90th days after the operation there were the changes of the resting membrane potential and amplitude of postsynaptic potentials developed by the stimulation of mechanosensory neuron. It is suggested that the leech nervous system serves as the dynamic formation depending on changes of neuronal ensemble structure.     

Integration of function in the nervous system — A new theory

A new theory of synaptic function in the nervous system (Dempsher, 1978) is applied to the simplest system for integration of function in the nervous system. This system includes a sensory and motor neuron and three ‘synaptic’ regions associated with those two neurons; a receptor region, an interneuronal spinal synaptic region linking the two neurons, and an effector region. Information is first received and processed at the receptor region. The processing consists of five components:

1. A highly selective mechanism which allows only that information to enter the receptor system which is appropriate.
2. The ‘appropriateness’ of the information is determined by the alphabet (miniature potentials) already in that area.
3. The information entering the system is assembled in a pattern meaningful for the next processing operation.
4. The assembled information is then ‘disassembled’ into its subunits and mapped into the alphabet (miniature potentials).
5. These miniature potentials are assembled into another pattern meaningful to fit the role of the receptor region.
6. This new pattern is repacked for transit to the central synaptic region.

At the central synaptic region, essentially the same process takes place except here an additional operation takes place which determines its role in the processing system. The incoming information is disassembled into its subunits, mapped into the miniature potentials already there; these are collected together in a meaningful pattern, ‘operated’ on, then repacked for transit to the effector site, where again the same kind of processing sequence takes place. In all three regions, despite the difference in their roles, there are similar processing features:

1. In each region, three forms of the nerve impulse are involved: miniature graded potentials, graded potentials, action potentials.
2. In each region, each component of the process is carried out by a precise mathematical operation: four each in the receptor and effector regions; five in the central synaptic region.

It is suggested that integration of function in the nervous system consists of converting information into energy which is in turn converted into a number. Processing of information at each region then involves mathematical operations applied to these numbers. Function appears to be stereotyped in all three regions. The receptor region receives highly selective and restrictive information so that the universe we ‘perceive’ would appear to be a subset of a much larger universe.     

Adaptive Spike Threshold Enables Robust and Temporally Precise Neuronal Encoding

Neural processing rests on the intracellular transformation of information as synaptic inputs are translated into action potentials. This transformation is governed by the spike threshold, which depends on the history of the membrane potential on many temporal scales. While the adaptation of the threshold after spiking activity has been addressed before both theoretically and experimentally, it has only recently been demonstrated that the subthreshold membrane state also influences the effective spike threshold. The consequences for neural computation are not well understood yet. We address this question here using neural simulations and whole cell intracellular recordings in combination with information theoretic analysis. We show that an adaptive spike threshold leads to better stimulus discrimination for tight input correlations than would be achieved otherwise, independent from whether the stimulus is encoded in the rate or pattern of action potentials. The time scales of input selectivity are jointly governed by membrane and threshold dynamics. Encoding information using adaptive thresholds further ensures robust information transmission across cortical states i.e. decoding from different states is less state dependent in the adaptive threshold case, if the decoding is performed in reference to the timing of the population response. Results from in vitro neural recordings were consistent with simulations from adaptive threshold neurons. In summary, the adaptive spike threshold reduces information loss during intracellular information transfer, improves stimulus discriminability and ensures robust decoding across membrane states in a regime of highly correlated inputs, similar to those seen in sensory nuclei during the encoding of sensory information.     

Individual personality-related characteristics of event-related EEG potentials recorded in an experimental situation requiring production of time intervals

Event-related EEG potentials (ERP) were recorded from 75 tested adult men and women; recording was performed from C3 and C4 points. The experimental situation required internal counting of time intervals limited by two pushes of a button. The experimental paradigm provided a substantial level of uncertainty, and a high level of attention needed to be maintained. The tested subjects were not informed by the experimenter about the precise value of the preset time interval; they knew only its limits, 17–23 sec. The subject obtained information about the agreement or disagreement between the produced interval and its value preset by the experimenter by visual feedback signals obtained 2 sec after termination of counting; in the case of agreement the subject had to perform a confirming (third) push of the button. Pushes were preceded by readiness potentials (RP); contingent negative variation (CNV) developed before the feedback signals, and the latter were accompanied by P300 potentials. Significant positive correlations were found between the parameters of RP and P300 in both hemispheres. In general, ERP were characterized by very high interindividual variability, which in a few respects correlated with the personality-related characteristics of tested subjects evaluated by psychological testing with the use of corresponding questionnaires. In particular, under the experimental conditions used, negative correlations were observed between the RP amplitude and psychotism indices, CNV amplitude and emotional stability; CNV amplitude and extroversive features, and P300 amplitude and domination properties of a person. Positive correlations were observed between the CNV amplitude and autia factor (according to Eysenck’s PEN and Cattell’s 16 PF questionnaires). We suppose that correlations between the personal psychical features and ERP parameters are grounded in both inherited constitutional specificities of the nervous system and neurochemical/structural modifications in the brain determined by the acquired vital experience.     

Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain.

Neurofibromatosis type 2 (NF2) is a dominantly inherited disease associated with the central nervous system. The NF2 gene product merlin is a tumor suppressor, and its mutation or inactivation causes this disease. We report here the crystal structure of the merlin FERM domain containing a 22-residue alpha-helical segment. The structure reveals that the merlin FERM domain consists of three subdomains displaying notable features of the electrostatic surface potentials, although the overall surface potentials similar to those of ezrin/radixin/moesin (ERM) proteins indicate electrostatic membrane association. The structure also is consistent with inactivation mechanisms caused by the pathogenic mutations associated with NF2.     

Transduction mechanisms in airway sensory nerves.

The induction of action potentials in airway sensory nerves relies on events leading to the opening of cation channels in the nerve terminal membrane and subsequent membrane depolarization. If the membrane depolarization is of sufficient rate and amplitude, action potential initiation will occur. The action potentials are then conducted to the central nervous system, leading to the initiation of various sensations and cardiorespiratory reflexes. Triggering events in airway sensory nerves include mechanical perturbation, inflammatory mediators, pH, temperature, and osmolarity acting through a variety of ionotropic and metabotropic receptors. Action potential initiation can be modulated (positively or negatively) through independent mechanisms caused mainly by autacoids and other metabotropic receptor ligands. Finally, gene expression of sensory nerves can be altered in adult mammals. This neuroplasticity can change the function of sensory nerves and likely involve both neurotrophin and use-dependent mechanisms. Here we provide a brief overview of some of the transduction mechanisms underlying these events.     

Sucrose-gap technique: Advantages and limitations

The sucrose-gap technique has been widely used as a convenient tool for recording of the membrane activities from myelinated or unmyelinated nerves and muscle preparations (such as smooth and cardiac muscles). The quantitative measurements of membrane and action potentials in preparations with electrical coupling between their compartments are made much easier by this technique; the recorded potentials are rather similar to those recorded with a microelectrode. Recording of the membrane activities is of great value to experimenters studying the nervous system due to the simplicity and ease of use of this technique and the broad spectrum of sensitivity to agents influencing the electrical activity. This paper is focused on the set-up procedure and operation of the sucrose-gap technique, which provides an inexpensive, practical, and effective method for the investigation of the effects of drugs on the membrane activities of nerves and muscles in vitro. Neirofiziologiya/Neurophysiology, Vol. 39, No. 3, pp. 270–274, May–June, 2007.     

神经元放电阈值的可变性及其意义

神经元能够将不同时空模式的突触输入转化为时序精确的动作电位输出，这种灵活、可靠的信息编码方式是神经集群在动态环境或特定任务下产生所需活动模式的重要基础。动作电位的产生遵循全或无规律，只有当细胞膜电压达到放电阈值时，神经元才产生动作电位。放电阈值在细胞内和细胞间具有高度可变性，具体动态依赖于刺激输入和放电历史。特别是，放电阈值对动作电位起始前的膜电压变化十分敏感，这种状态依赖性产生的生物物理根源包括Na⁺失活和K⁺激活。在绝大多数神经元中，动作电位的触发位置是轴突起始端，这个位置处的阈值可变性是决定神经元对时空输入转化规律的关键因素。但是，电生理实验中动作电位的记录位置却通常是胞体或近端树突，此处的阈值可变性高于轴突起始端，而其产生的重要根源是轴突动作电位的反向传播。基于胞体测量的相关研究显示，放电阈值动态能够增强神经元的时间编码、特征选择、增益调控和同时侦测能力。本文首先介绍放电阈值的概念及量化方法，然后详细梳理近年来国内外关于放电阈值可变性及产生根源的研究进展，在此基础上归纳总结放电阈值可变性对神经元编码的重要性，最后对未来放电阈值的研究方向进行展望。     

Methods for patch clamp capacitance recordings from the calyx

We demonstrate the basic techniques for presynaptic patch clamp recording at the calyx of Held, a mammalian central nervous system nerve terminal. Electrical recordings from the presynaptic terminal allow the measurement of action potentials, calcium channel currents, vesicle fusion (exocytosis) and subsequent membrane uptake (endocytosis). The fusion of vesicles containing neurotransmitter causes the vesicle membrane to be added to the cell membrane of the calyx. This increase in the amount of cell membrane is measured as an increase in capacitance. The subsequent reduction in capacitance indicates endocytosis, the process of membrane uptake or removal from the calyx membrane. Endocytosis, is necessary to maintain the structure of the calyx and it is also necessary to form vesicles that will be filled with neurotransmitter for future exocytosis events. Capacitance recordings at the calyx of Held have made it possible to directly and rapidly measure vesicular release and subsequent endocytosis in a mammalian CNS nerve terminal. In addition, the corresponding postsynaptic activity can be simultaneously measured by using paired recordings. Thus a complete picture of the presynaptic and postsynaptic electrical activity at a central nervous system synapse is achievable using this preparation. Here, the methods for slice preparation, morphological features for identification of calyces of Held, basic patch clamping techniques, and examples of capacitance recordings to measure exocytosis and endocytosis are presented.     

A new method to infer higher-order spike correlations from membrane potentials

What is the role of higher-order spike correlations for neuronal information processing? Common data analysis methods to address this question are devised for the application to spike recordings from multiple single neurons. Here, we present a new method which evaluates the subthreshold membrane potential fluctuations of one neuron, and infers higher-order correlations among the neurons that constitute its presynaptic population. This has two important advantages: Very large populations of up to several thousands of neurons can be studied, and the spike sorting is obsolete. Moreover, this new approach truly emphasizes the functional aspects of higher-order statistics, since we infer exactly those correlations which are seen by a neuron. Our approach is to represent the subthreshold membrane potential fluctuations as presynaptic activity filtered with a fixed kernel, as it would be the case for a leaky integrator neuron model. This allows us to adapt the recently proposed method CuBIC (cumulant based inference of higher-order correlations from the population spike count; Staude et al., J Comput Neurosci 29(1–2):327–350, 2010c) with which the maximal order of correlation can be inferred. By numerical simulation we show that our new method is reasonably sensitive to weak higher-order correlations, and that only short stretches of membrane potential are required for their reliable inference. Finally, we demonstrate its remarkable robustness against violations of the simplifying assumptions made for its construction, and discuss how it can be employed to analyze in vivo intracellular recordings of membrane potentials.     

The Nodes of Ranvier: Molecular Assembly and Maintenance

Action potential (AP) propagation in myelinated nerves requires clustered voltage gated sodium and potassium channels. These channels must be specifically localized to nodes of Ranvier where the AP is regenerated. Several mechanisms have evolved to facilitate and ensure the correct assembly and stabilization of these essential axonal domains. This review highlights the current understanding of the axon intrinsic and glial extrinsic mechanisms that control the formation and maintenance of the nodes of Ranvier in both the peripheral nervous system (PNS) and central nervous system (CNS).Axons conduct electrical signals, called action potentials (APs), among neurons in a circuit in response to sensory input, and between motor neurons and muscles. In mammals and other vertebrates, many axons are myelinated. Myelin, made by Schwann cells and oligodendrocytes in the peripheral nervous system (PNS) and central nervous system (CNS), respectively, is a multilamellar sheet of glial membrane that wraps around axons to increase transmembrane resistance and decrease membrane capacitance. Although myelin is traditionally viewed as a passive contributor to nervous system function, it is now recognized that myelinating glia also play many active roles including regulation of axon diameter, axonal energy metabolism, and the clustering of ion channels at gaps in the myelin sheath called nodes of Ranvier. Together, the active and passive properties conferred on axons by myelin, result in axons with high AP conduction velocities, low metabolic demands, and reduced space requirements as compared with unmyelinated axons. Thus, myelin and the clustering of ion channels in axons permitted the evolution of the complex nervous systems found in vertebrates. This review highlights the current understanding of the axonal intrinsic and glial extrinsic mechanisms that control the formation and maintenance of the nodes of Ranvier in both the PNS and CNS.     

Constant brain potentials as neurophysiological markers of autoimmune process]

Neuroimmune interactions in systemic rheumatic diseases were studied. The state of the central nervous system was assessed from the parameters of constant brain potentials, and the state of the immune system, from a complex of immunobiochemical parameters. The highest multiple correlation coefficients were revealed between the immunobiochemical parameters and the parameters of the constant brain potential, which characterize linear and standard deviations of potentials in temporal zones from potentials at other points of recording. The results are discussed in terms of structural and functional integration of the immune and nervous systems.     

BDNF boosts spike fidelity in chaotic neural oscillations

Oscillatory activity and its nonlinear dynamics are of fundamental importance for information processing in the central nervous system. Here we show that in aperiodic oscillations, brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, enhances the accuracy of action potentials in terms of spike reliability and temporal precision. Cultured hippocampal neurons displayed irregular oscillations of membrane potential in response to sinusoidal 20-Hz somatic current injection, yielding wobbly orbits in the phase space, i.e., a strange attractor. Brief application of BDNF suppressed this unpredictable dynamics and stabilized membrane potential fluctuations, leading to rhythmical firing. Even in complex oscillations induced by external stimuli of 40 Hz (gamma) on a 5-Hz (theta) carrier, BDNF-treated neurons generated more precisely timed spikes, i.e., phase-locked firing, coupled with theta-phase precession. These phenomena were sensitive to K252a, an inhibitor of tyrosine receptor kinases and appeared attributable to BDNF-evoked Na(+) current. The data are the first indication of pharmacological control of endogenous chaos. BDNF diminishes the ambiguity of spike time jitter and thereby might assure neural encoding, such as spike timing-dependent synaptic plasticity.     

nsf is essential for organization of myelinated axons in zebrafish

BACKGROUND: Myelinated axons are essential for rapid conduction of action potentials in the vertebrate nervous system. Of particular importance are the nodes of Ranvier, sites of voltage-gated sodium channel clustering that allow action potentials to be propagated along myelinated axons by saltatory conduction. Despite their critical role in the function of myelinated axons, little is known about the mechanisms that organize the nodes of Ranvier. RESULTS: Starting with a forward genetic screen in zebrafish, we have identified an essential requirement for nsf (N-ethylmaleimide sensitive factor) in the organization of myelinated axons. Previous work has shown that NSF is essential for membrane fusion in eukaryotes and has a critical role in vesicle fusion at chemical synapses. Zebrafish nsf mutants are paralyzed and have impaired response to light, reflecting disrupted nsf function in synaptic transmission and neural activity. In addition, nsf mutants exhibit defects in Myelin basic protein expression and in localization of sodium channel proteins at nodes of Ranvier. Analysis of chimeric larvae indicates that nsf functions autonomously in neurons, such that sodium channel clusters are evident in wild-type neurons transplanted into the nsf mutant hosts. Through pharmacological analyses, we show that neural activity and function of chemical synapses are not required for sodium channel clustering and myelination in the larval nervous system. CONCLUSIONS: Zebrafish nsf mutants provide a novel vertebrate system to investigate Nsf function in vivo. Our results reveal a previously unknown role for nsf, independent of its function in synaptic vesicle fusion, in the formation of the nodes of Ranvier in the vertebrate nervous system.     

Synchronous membrane potential fluctuations in neurons of the cat visual cortex

We have recorded intracellularly from pairs of neurons less than 500 microm distant from one another in V1 of anesthetized cats. Cross-correlation of spontaneous fluctuations in membrane potential revealed significant correlations between the cells in each pair. This synchronization was not dependent on the occurrence of action potentials, indicating that it was not caused by mutual interconnections. The cells were synchronized continuously rather than for brief epochs. Much weaker correlations were found between the EEG and intracellular potentials, suggesting local, rather than global, synchrony. The highest correlation occurred among cells with similar connectivity from the LGN and similar receptive fields. During visual stimulation, correlations increased when both cells responded to the stimulus and decreased when neither cell responded.     

Qualitative Behavior of Spontaneous Potentials from Explants of 15 Day Chick Embryo Telencephalon in Vitro

The apparatus and technique used in the preparation and observation of explants of brain tissue capable of producing spontaneous potentials in vitro are described. The magnitude and pattern of spontaneous potentials from explants of telencephalon of 15 day chick embryos (measured using external bare platinum electrodes) and some aspects of their "normal" behavior during 12 days in vitro are also described. No change was noted in these potentials with change of amplifiers, recorders, or electrodes. The response of the potentials to change in temperature and proportionate composition of the atmosphere around the explant was such as to suggest that the potentials arise as a result of a living process. The changes brought about by the administration of anesthetics, strychnine, brucine, and barbiturates were those that might be anticipated in a normal functional activity of the central nervous system. It is concluded that these potentials are a true physiological phenomenon and arise from living cells of the central nervous system.     

Cutting-edge technology. III. Imaging and the gastrointestinal tract: mapping the human enteric nervous system

Monitoring membrane potentials by multisite optical recording techniques using voltage-sensitive dyes is ideal for direct analysis of network signaling. We applied this technology to monitor fast and slow excitability changes in the enteric nervous system and in hundreds of neurons simultaneously at cellular and subcellular resolution. This imaging technique presents a powerful tool to study activity patterns in enteric pathways and to assess differential activation of nerves in the gut to a number of stimuli that modulate neuronal activity directly or through synaptic mechanisms. The optical mapping made it possible to record from tissues such as human enteric nerves, which were, until now, inaccessible by other techniques.     

A comparative analysis of the effect of an analog of vasopressin on functionally different neurons in the grape snail

Application of desglycine-argininvasopressin (DG-AVP) differently influenced different types of cells of snail isolated central nervous system. In neurosecretory cells an increase of spontaneous impulse activity took place and, as a rule, bursts of impulses appeared, most often of synaptic origin, excluding PPa1 neurones and one of the neurosecretory cells of the left parietal ganglion. The increase of the bursts activity in these cells was based on the increase of the amplitude of membrane potential waves. Under the influence of neurosecretory cells system activation, EPSPs frequency and amplitude in secondary-sensory neurones increased, which led to a greater probability of the action potentials appearance. At prolonged action the spontaneous EPSPs in these cells began to group in bursts. Excitability and membrane resistance of these cells remained unchanged. DG-AVP had no influence on primary-sensory neurones and motoneurones.