Extra spike formation in sensory neurons and the disruption of afferent spike patterning

The peculiar pseudounipolar geometry of primary sensory neurons can lead to ectopic generation of "extra spikes" in the region of the dorsal root ganglion potentially disrupting the fidelity of afferent signaling. We have used an explicit model of myelinated vertebrate sensory neurons to investigate the location and mechanism of extra spike formation, and its consequences for distortion of afferent impulse patterning. Extra spikes originate in the initial segment axon under conditions in which the soma spike becomes delayed and broadened. The broadened soma spike then re-excites membrane it has just passed over, initiating an extra spike which propagates outwards into the main conducting axon. Extra spike formation depends on cell geometry, electrical excitability, and the recent history of impulse activity. Extra spikes add to the impulse barrage traveling toward the spinal cord, but they also travel antidromically in the peripheral nerve colliding with and occluding normal orthodromic spikes. As a result there is no net increase in afferent spike number. However, extra spikes render firing more staccato by increasing the number of short and long interspike intervals in the train at the expense of intermediate intervals. There may also be more complex changes in the pattern of afferent spike trains, and hence in afferent signaling.     

Role of A-type K+ channels in spike broadening observed in soma and axon of Hermissenda type-B photoreceptors: A simulation study

In Hermissenda type-B photoreceptors, the spike is generated in the axon and back-propagated to the soma, resulting in smaller somatic spikes. Experimentally, blocking the A-type K⁺ current (I_K,A) results in broadening of somatic spikes. Similarly, in a compartmental model of the photoreceptor, reducing the maximum A-type K⁺ conductance (g_K,Amax) results in broadening of somatic spikes. However, simulations predict that little or no broadening of axonal spikes occurs when g_K,Amax is reduced. The results can be explained by the voltage-dependent properties of I_K,A and the different potential ranges that the somatic and axonal spike traverse. Because of the steeper I-V curve and faster activation of the K⁺ channels at higher potentials, the recruitment of additional K⁺ channels in the axon is able to compensate for the decrease in K⁺ conductance, yielding less spike broadening. These results also support the idea that spike duration in the axon may not be reliably inferred based upon recordings collected from the soma. Action Editor: Jonathan D. Victor     

Sharpness of Spike Initiation in Neurons Explained by Compartmentalization

In cortical neurons, spikes are initiated in the axon initial segment. Seen at the soma, they appear surprisingly sharp. A standard explanation is that the current coming from the axon becomes sharp as the spike is actively backpropagated to the soma. However, sharp initiation of spikes is also seen in the input–output properties of neurons, and not only in the somatic shape of spikes; for example, cortical neurons can transmit high frequency signals. An alternative hypothesis is that Na channels cooperate, but it is not currently supported by direct experimental evidence. I propose a simple explanation based on the compartmentalization of spike initiation. When Na channels are placed in the axon, the soma acts as a current sink for the Na current. I show that there is a critical distance to the soma above which an instability occurs, so that Na channels open abruptly rather than gradually as a function of somatic voltage.     

Conduction velocity and spike duration during afterdischarge in neuroendocrine bag cells of Aplysia

Changes in conduction velocity and spike duration during electrically triggered afterdischarges were determined with extracellular recordings from bag-cell neurites of Aplysia. Spikes with high conduction velocity and short duration occurred at the onset of the afterdischarge during the period of high-frequency firing and regular interspike intervals. Later in the afterdischarge, spike frequency and conduction velocity decreased, while spike duration increased. During the short bursts within the later part of the afterdischarge, conduction velocity was highest for the first spike and decreased for successive spikes in the burst. That conduction velocity and spike frequency were both maximal during the first minute of the afterdischarge and lower during the later periods of the spike train supports the hypothesis that changes in the excitability of the bag-cell neurites occur during this firing pattern. Furthermore, the slower conduction velocity and longer duration of spikes from the bag-cell neurites late in the afterdischarge, and late in the individual bursts within the afterdischarge, suggest the hypothesis of enhanced hormone release per action potential during these periods.     

Axons Amplify Somatic Incomplete Spikes into Uniform Amplitudes in Mouse Cortical Pyramidal Neurons

Background

Action potentials are the essential unit of neuronal encoding. Somatic sequential spikes in the central nervous system appear various in amplitudes. To be effective neuronal codes, these spikes should be propagated to axonal terminals where they activate the synapses and drive postsynaptic neurons. It remains unclear whether these effective neuronal codes are based on spike timing orders and/or amplitudes.

Methodology/Principal Findings

We investigated this fundamental issue by simultaneously recording the axon versus soma of identical neurons and presynaptic vs. postsynaptic neurons in the cortical slices. The axons enable somatic spikes in low amplitude be enlarged, which activate synaptic transmission in consistent patterns. This facilitation in the propagation of sequential spikes through the axons is mechanistically founded by the short refractory periods, large currents and high opening probability of axonal voltage-gated sodium channels.

Conclusion/Significance

An amplification of somatic incomplete spikes into axonal complete ones makes sequential spikes to activate consistent synaptic transmission. Therefore, neuronal encoding is likely based on spike timing order, instead of graded analogues.     

Neural mechanisms underlying behavior in the locust Schistocerca gregaria I. Physiology of identified motorneurons in the metathoracic ganglion

A preparation of the desert locust, Schistocera gregaria, has been developed, in which it was possible to work with identified neurons while still allowing some behavior. A total of 26 motorneurons to the hind leg were studied singly, and in various pairs, both by direct stimulation, and by recording during spontaneous activity and various reflex actions. Motorneurons were identified by passing current into their somata and correlating the evoked somata spikes with extracellularly or intracellularly recorded events in the muscles. Tension of the muscle was also recorded and motor axons were stimulated to evoke antidromic spikes in the somata. Both epsp's and ipsp's can be seen clearly in recordings from the somata; spikes appear as electrotonically conducted remnants only. Somata exhibited little or no electrogenesis. It is inferred that impulses are initiated in a zone tentatively identified with the region of emergence of the motor axon from the neuropil. Integration occurs in the neuropilar segment, with the soma serving as a parallel RC element. Data was obtained on the central mechanisms of coordination of synergistic and antagonistic motorneurons and on the modes of excitation of slow and fast neurons to the same muscles.     

A re-excitation mechanism for strychnine-induced doublets in molluscan neurons

The effects of strychnine on Aplysia R2 neurons were evaluated using simultaneous intracellular recordings of the soma and axon potentials. 1 mM strychnine produced a slight enlargement of the somatic spike and a large increase of the axon spike duration. Following direct stimulation, the soma displayed depolarizing afterpotentials ( DAPs ) which might trigger extra-spikes, both produced electronically by long-lasting axon spikes. Cobalt suppressed both the axon spike lengthening and the somatic extra-spikes or DAPs , and induced large depolarizing shifts in the soma. The region of largest spike lengthening (proximal axon) had a large density of Ca channels. The different effects of strychnine on the soma and on the axon were assumed to result from a selective blockage of the V-dependent K channels which would predominate in the axon whereas Ca-activated K channels would predominate in the soma.     

Thalamocortical control of feed-forward inhibition in awake somatosensory 'barrel' cortex

Intracortical inhibition plays a role in shaping sensory cortical receptive fields and is mediated by both feed-forward and feedback mechanisms. Feed-forward inhibition is the faster of the two processes, being generated by inhibitory interneurons driven by monosynaptic thalamocortical (TC) input. In principle, feed-forward inhibition can prevent targeted cortical neurons from ever reaching threshold when TC input is weak. To do so, however, inhibitory interneurons must respond to TC input at low thresholds and generate spikes very quickly. A powerful feed-forward inhibition would sharpen the tuning characteristics of targeted cortical neurons, and interneurons with sensitive and broadly tuned receptive fields could mediate this process. Suspected inhibitory interneurons (SINs) with precisely these properties are found in layer 4 of the somatosensory (S1) 'barrel' cortex of rodents and rabbits. These interneurons lack the directional selectivity seen in most cortical spiny neurons and in ventrobasal TC afferents, but are much more sensitive than cortical spiny neurons to low-amplitude whisker displacements. This paper is concerned with the activation of S1 SINs by TC impulses, and with the consequences of this activation. Multiple TC neurons and multiple S1 SINs were simultaneously studied in awake rabbits, and cross-correlation methods were used to examine functional connectivity. The results demonstrate a potent, temporally precise, dynamic and highly convergent/divergent functional input from ventrobasal TC neurons to SINs of the topographically aligned S1 barrel. Whereas the extensive pooling of convergent TC inputs onto SINs generates sensitive and broadly tuned inhibitory receptive fields, the potent TC divergence onto many SINs generates sharply synchronous activity among these elements. This TC feed-forward inhibitory network is well suited to provide a fast, potent, sensitive and broadly tuned inhibition of targeted spiny neurons that will suppress spike generation following all but the most optimal feed-forward excitatory inputs.     

Effects of temperan a central synapse between identified motor neurons in the locust

Summary Changing the temperature from 10–40 °C modifies the transmission at an established monosynaptic connection between the fast extensor tibiae (FETi) and flexor tibiae motor neurons in the metathoracic ganglion of the locustSchistocerca gregaria (Forskål). Striking changes occur to the shape of the spikes, to membrane resistance, to the synaptic delay, and to the evoked synaptic potentials.In the presynaptic FETi motor neuron, raising the temperature reduces the amplitude of an antidromic spike recorded in the soma by a factor of 10 (40 mV to 4 mV), reduces the time taken to reach peak amplitude by 5 (3.5 to 0.7 ms) and decreases the duration at half maximum amplitude by 0.5. The conduction velocity of the spike in the axon is increased by 50% from 10 °C to 40 °C. Orthodromic spikes are affected by temperature in a similar way to the antidromic spikes.The membrane resistance of both pre- and postsynaptic motor neurons falls as the temperature is raised. The membrane resistance of FETi falls by a factor of 4 (about 4 M at 10 °C to 1 M at 40 °C). A contributory component to this fall could be the increase in the frequency of synaptic potentials generated as a result of inputs from other neurons. No temperature dependence could be demonstrated on the voltage threshold relative to resting potential for evoking orthodromic spikes, but because the resistance changes, the current needed to achieve this voltage must be increased at higher temperatures.The latency measured from the peak of the spike in the soma of FETi to the start of the EPSP in the soma of a flexor motor neuron decreases by a factor of 20 (10 ms at 10 °C to 0.5 ms at 40 °C).In a postsynaptic flexor tibiae motor neuron, the amplitude of the evoked synaptic potential increases by a factor of 3.4 (5 mV to 17 mV), its duration at half maximum amplitude decreases by 3 (7 ms at 12 °C to 2.3 ms at 32 °C) and its rate of rise increases by 3. An increased likelihood that spikes will occur in the flexor contributes to the enhanced amplitude of the compound EPSP at temperatures above 20 °C.Abbreviation FETi fast extensor tibiae motor neuron     

Computational Model of Touch Sensory Cells (T Cells) of the Leech: Role of the Afterhyperpolarization (AHP) in Activity-Dependent Conduction Failure

Bursts of spikes in T cells produce an AHP, which results from activation of a Na⁺/K⁺ pump and a Ca²⁺-dependent K⁺ current. Activity-dependent increases in the AHP are believed to induce conduction block of spikes in several regions of the neuron, which in turn, may decrease presynaptic invasion of spikes and thereby decrease transmitter release. To explore this possibility, we used the neurosimulator SNNAP to develop a multi-compartmental model of the T cell. The model incorporated empirical data that describe the geometry of the cell and activity-dependent changes of the AHP. Simulations indicated that at some branching points, activity-dependent increases of the AHP reduced the number of spikes transmitted from the minor receptive fields to the soma and beyond. More importantly, simulations also suggest that the AHP could modulate, under some circumstances, transmission from the soma to the synaptic terminals, suggesting that the AHP can regulate spike conduction within the presynaptic arborizations of the cell and could in principle contribute to the synaptic depression that is correlated with increases in the AHP.     

A prolonged,voltage-dependent calcium permeability revealed by tetraethylammonium in the soma and axon of Aplysia giant neuron

The soma but not the axon of the giant neuron, R2, of Aplysia can generate an all-or-none Ca spike in Na-free or TTX-containing medium (Junge and Miller, 1974). Extracellular axonal recordings made at several distances from the soma provide evidence that the transition in ability to fire a spike in Na-free medium occurs within the first 250 μm of the axon. Application of 25 mM TEA-Br to the bathing medium causes a more than tenfold increase in the duration of the somatic action potential. The duration of the axonal action potential in TEA decreases with distance from the soma. At distances greater than 3 mm from the soma this concentration of TEA causes little or no increase in the duration of the axon spike. The effect of 25 mM TEA on both the soma and proximal axon is blocked reversibly by 30 mM CoCl₂ or 1 mM CdCl₂. The duration of the somatic action potential in TEA increases with an increase in Ca concentration of the bath. At a constant concentration of Na, the voltage level of the somatic plateau increases with Ca concentration in the manner predicted for a Ca electrode. In the presence of 11 mM Ca²⁺ the potential of the plateau is relatively insensitive to Na concentration. The TEA plateau in R2 reveals a prolonged voltage-dependent permeability to Ca. The duration of the plateau may indicate the degree of Ca activation during a spike.     

Comparison of motor patterns in the intact and deafferented flight system of the locust

Summary The activity of flight interneurons was recorded intracellularly in intact, tethered flying locusts (Locusta migratoria) and after removal of sensory input from the wing receptors. Depolarization patterns and spike discharges were characterized and compared for the two situations.In general, depressor interneurons (n=6) showed only minor changes in their activity as a result of deafferentation (Fig. 1). Exceptions were interneurons 308 and 506 (Fig. 2). By contrast, all but one of the elevator interneurons (n=9) produced distinctly different depolarization patterns in intact locusts and following deafferentation. Three different groups of elevator interneurons were found (excluding the one exceptional neuron, Fig. 6). (i) One group of interneurons (n=4) produced different, superthreshold depolarizations in intact and deafferented animals (Fig. 3). Characteristic, biphasic depolarizations were recorded from these fibres at lower wingbeat frequencies in the intact situation but only single, delayed potentials were recorded after deafferentation. (ii) The second group of interneurons (n=3) exhibited distinct rhythmic activity only in intact animals. After deafferentation their depolarizations were small and often below the threshold for spike initiation (Fig. 4). (iii) One interneuron produced rhythmic flight motor oscillations only after deafferentation. In intact locusts the membrane potential of this neuron showed very small oscillations and remained subthreshold (Fig. 5).Four main conclusions emerge from these data. (i) The activity of elevator interneurons is under greater sensory control than that of the depressors. This confirms the results of our previous electromyographic and motoneuronal analyses, (ii) A considerable portion of elevator activity is generated as a result of phasic sensory feedback. An essential input is from the hindwing tegulae (Table 1; Pearson and Wolf 1988). (iii) The activity of depressor interneurons appears to be determined by central mechanisms to a major extent. (iv) Different sets of central neurons appear to be involved in flight pattern generation in intact and deafferented locusts —although the two sets share many common elements.Abbreviations EMG electromyogram - PSP postsynaptic potential (EPSP excitatory andIPSP inhibitory)     

Amplitude variability and extracellular low-pass filtering of neuronal spikes

The influence of neural morphology and passive electrical parameters on the width and amplitude of extracellular spikes is investigated by combined analytical and numerical investigations of idealized and anatomically reconstructed pyramidal and stellate neuron models. The main results are: 1), All models yield a low-pass filtering effect, that is, a spike-width increase with increasing distance from soma. 2), A neuron's extracellular spike amplitude is seen to be approximately proportional to the sum of the dendritic cross-sectional areas of all dendritic branches connected to the soma. Thus, neurons with many, thick dendrites connected to soma will produce large amplitude spikes, and therefore have the largest radius of visibility. 3), The spike shape and amplitude are found to be dependent on the membrane capacitance and axial resistivity, but not on the membrane resistivity. 4), The spike-amplitude decay with distance r is found to depend on dendritic morphology, and is decaying as 1/rⁿ with 1 ≤ n ≤ 2 close to soma and n ≥ 2 far away.     

Modes of Initiation and Propagation of Spikes in the Branching Axons of Molluscan Central Neurons

A study has been made of Aplysia nerve cells, mainly in the pleural ganglia, in which the main axon divides into at least two branches in the neighbourhood of the soma. Conduction between these branches was investigated by intracellular recordings from the soma following antidromic stimulation via the nerves containing the axonal branches. It has been shown that transmission between separate branches need not involve discharge of the soma but only of the axonal region between the soma and the origin of the branches. In some cells, the spike may fail to invade the other axonal branch, whereas transmission in the opposite direction is readily achieved. Often spikes in none of the branches are transmitted to the others, unless facilitated. Indications about the geometry of the neuron in the vicinity of the soma may be obtained from the study of the relative size of the A spikes originated in different branches. These observations, together with the presence of different sizes of A spikes, produced by orthodromic stimulation, provide evidence that spikes initiated at separate axonal "trigger zones" of Aplysia neurons may be conducted selectively to the effectors or other neurons innervated by the particular branch.     

Active dendritic conductances dynamically regulate GABA release from thalamic interneurons

Inhibitory interneurons in the dorsal lateral geniculate nucleus (dLGN) process visual information by precisely controlling spike timing and by refining the receptive fields of thalamocortical (TC) neurons. Previous studies indicate that dLGN interneurons inhibit TC neurons by releasing GABA from both axons and dendrites. However, the mechanisms controlling GABA release are poorly understood. Here, using simultaneous whole-cell recordings from interneurons and TC neurons and two-photon calcium imaging, we find that synchronous activation of multiple retinal ganglion cells (RGCs) triggers sodium spikes that propagate throughout interneuron axons and dendrites, and calcium spikes that invade dendrites but not axons. These distinct modes of interneuron firing can trigger both a rapid and a sustained component of inhibition onto TC neurons. Our studies suggest that active conductances make LGN interneurons flexible circuit-elements that can shift their spatial and temporal properties of GABA release in response to coincident activation of functionally related subsets of RGCs.     

A model for the neuronal implementation of selective visual attention based on temporal correlation among neurons

We propose a model for the neuronal implementation of selective visual attention based on temporal correlation among groups of neurons. Neurons in primary visual cortex respond to visual stimuli with a Poisson distributed spike train with an appropriate, stimulus-dependent mean firing rate. The spike trains of neurons whose receptive fields donot overlap with the focus of attention are distributed according to homogeneous (time-independent) Poisson process with no correlation between action potentials of different neurons. In contrast, spike trains of neurons with receptive fields within the focus of attention are distributed according to non-homogeneous (time-dependent) Poisson processes. Since the short-term average spike rates of all neurons with receptive fields in the focus of attention covary, correlations between these spike trains are introduced which are detected by inhibitory interneurons in V4. These cells, modeled as modified integrate-and-fire neurons, function as coincidence detectors and suppress the response of V4 cells associated with non-attended visual stimuli. The model reproduces quantitatively experimental data obtained in cortical area V4 of monkey by Moran and Desimone (1985).     

Site of Origin and Propagation of Spike in the Giant Neuron of Aplysia

The form and time sequence of spikes generated by orthodromic, antidromic, and direct stimulation and during spontaneous activity have been studied with intracellular electrodes simultaneously introduced in the soma and in different parts of the axon of the giant nerve cell of Aplysia. Evidence was obtained that under normal conditions of excitability, the spike originates at some distance from the soma in an axonal region with a higher excitability surpassing that of the surrounding membranes. Between the trigger zone and the soma is situated a region of transitional excitability where the conduction of the spike towards the soma may be blocked at a functionally determined and variable locus. The cell body is electrically excitable, but has the highest threshold of all parts of the neuron. The inactivation or even the removal of the cell body does not suppress synaptic transmission.     

Steps in the production of motoneuron spikes

1. Spikes evoked in spinal motoneurons by antidromic stimulation normally present an inflection in their rising phase. A similar inflection is present in spikes evoked by direct stimulation with short pulses. 2. In either case the inflection becomes less prominent if the motoneuron membrane is depolarized and more prominent when it is hyperpolarized. Both antidromic and direct spikes may fall from the level of the inflection thus evoking a "small spike" only if sufficient hyperpolarization is applied. Similar events occur when antidromic or direct spikes are evoked in the aftermath of a preceding spike. 3. Spikes evoked by direct stimuli applied shortly after firing of a "small spike" may also become partially blocked at a critical stimulus interval. At shorter intervals, however, spike size again increases and no inflection can be detected in the rising phase. 4. When a weak direct stimulus evokes a small spike only, a stronger stimulus may evoke a full spike. Curves of the strength of the stimuli required for eliciting small or full spikes have been constructed in a number of conditions. 5. To explain the results it is assumed that threshold of the major portions of the soma membrane is higher than the threshold of the axon, the transition occurring over a finite area near the axon hillock. Following antidromic or direct stimulation, soma excitation is then initiated in the region of the axon hillock. Spread of activity towards the soma occurs at first slowly and with low safety factor. At this stage block may be easily evoked. Safety factor for propagation increases rapidly as the growing impulse involves larger and larger areas of the soma membrane so that, once the critical areas are excited, activation of the remaining portions of the soma membrane will suddenly occur.     

Identification of Active Membrane Areas in the Giant Neuron of Aplysia

Intracellular and extracellular potentials were simultaneously recorded from the soma and different parts of the axon of the giant cell of Aplysia. Evidence was obtained that for all modes of stimulation the spike originates in the axon at some distance from the cell body. The conduction of the spike is blocked at a distance of 200 to 300 µ from the soma for the antidromic spike, closer to the soma for an orthodromic spike. This event is recorded in the soma as a small or A spike. After some delay, a spike is initiated in the resting part of the axon and in the axon hillock; the soma is invaded only afterwards. The response of these three parts of the neuron is recorded in the soma as the big or S spike.     

Morphology and physiology of peripheral giant interneurons in the forelegs (whips) of the whip spider Heterophrynus elaphus Pocock (Arachnida: Amblypygi)

Summary The tarsi of the modified front legs (whips) of the whip spider Heterophrynus elaphus contain two afferent giant fibers, GN1 and GN2, with diameters at the tibia-tarsus joint of ca. 21 m and 14 m, respectively. The somata of these two neurons lie in the periphery, about 25 cm away from the CNS. These two neurons are interneurons which receive mechanoreceptive inputs from approximately 750 and 1500 bristles, respectively. The receptive fields of GN1 and GN2 overlap; they extend for 40 mm (GN1) and 90 mm (GN2) along the length of the tarsus. About 90% of the synapses onto the giant fibers are axo-axonic. Mechanical stimulation of a single bristle is sufficient to elicit action potentials in one or both interneurons. The response of the interneurons adapts quickly. Average conduction time from the soma to the CNS is 45 ms for GN1 and 55 ms for GN2. Mean conduction velocities are 5.5 and 4.2 m/s, respectively. Activity in the giant fibers does not elicit a motor response; hence the giant fibers do not mediate an escape response. Possible functions of these giant fibers are discussed and compared to those of giant fiber systems in other arthropods.Abbreviations GN giant neuron - S segment