Spike-triggered dendritic calcium transients depend on synaptic activity in the cricket giant interneurons.

The relationship between electrical activity and spike-induced Ca2+ increases in dendrites was investigated in the identified wind-sensitive giant interneurons in the cricket. We applied a high-speed Ca2+ imaging technique to the giant interneurons, and succeeded in recording the transient Ca2+ increases (Ca2+ transients) induced by a single action potential, which was evoked by presynaptic stimulus to the sensory neurons. The dendritic Ca2+ transients evoked by a pair of action potentials accumulated when spike intervals were shorter than 100 ms. The amplitude of the Ca2+ transients induced by a train of spikes depended on the number of action potentials. When stimulation pulses evoking the same numbers of action potentials were separately applied to the ipsi- or contra-lateral cercal sensory nerves, the dendritic Ca2+ transients induced by these presynaptic stimuli were different in their amplitude. Furthermore, the side of presynaptic stimulation that evoked larger Ca2+ transients depended on the location of the recorded dendritic regions. This result means that the spike-triggered Ca2+ transients in dendrites depend on postsynaptic activity. It is proposed that Ca2+ entry through voltage-dependent Ca2+ channels activated by the action potentials will be enhanced by excitatory synaptic inputs at the dendrites in the cricket giant interneurons.     

Role of an A-Type K+ Conductance in the Back-Propagation of Action Potentials in the Dendrites of Hippocampal Pyramidal Neurons

Action potentials elicited in the axon actively back-propagate into the dendritic tree. During this process their amplitudes can be modulated by internal and external factors. We used a compartmental model of a hippocampal CA1 pyramidal neuron to illustrate how this modulation could depend on (1) the properties of an A-type K⁺ conductance that is expressed at high density in hippocampal dendrites and (2) the relative timing of synaptic activation. The simulations suggest that the time relationship between pre- and postsynaptic activity could help regulate the amplitude of back-propagating action potentials, especially in the distal portion of the dendritic tree.     

Spatial and temporal analysis of calcium-dependent electrical activity in guinea pig Purkinje cell dendrites

We have used the calcium indicator dye arsenazo III, together with a photodiode array, to record intracellular calcium changes simultaneously from all regions of individual guinea pig cerebellar Purkinje cells in slices. The optical signals, recorded with millisecond time resolution, are good indicators of calcium-dependent electrical events. For many cells the sensitivity of the recordings was high enough to detect signals from each array element without averaging. Consequently, it was possible to use these signals to follow the complex spatial and temporal patterns of plateau and spike potentials. Calcium entry corresponding to action potentials was detected from all parts of the dendritic field including the fine spiny branchlets, demonstrating that calcium action potentials spread over the entire arbor. Usually, the entire dendritic tree fired at once. But sometimes only restricted areas had signals at any one moment with transients detected in different regions at other times. In one cell, six separate zones were distinguished. These results show that calcium action potentials could be regenerative in some dendrites and could fail to propagate into others. Signals from plateau potentials were also detected from extensive areas in the dendritic field but were always smaller than those caused by a burst of action potentials.     

Spike‐triggered dendritic calcium transients depend on synaptic activity in the cricket giant interneurons

The relationship between electrical activity and spike‐induced Ca²⁺ increases in dendrites was investigated in the identified wind‐sensitive giant interneurons in the cricket. We applied a high‐speed Ca²⁺ imaging technique to the giant interneurons, and succeeded in recording the transient Ca²⁺ increases (Ca²⁺ transients) induced by a single action potential, which was evoked by presynaptic stimulus to the sensory neurons. The dendritic Ca²⁺ transients evoked by a pair of action potentials accumulated when spike intervals were shorter than 100 ms. The amplitude of the Ca²⁺ transients induced by a train of spikes depended on the number of action potentials. When stimulation pulses evoking the same numbers of action potentials were separately applied to the ipsi‐ or contra‐lateral cercal sensory nerves, the dendritic Ca²⁺ transients induced by these presynaptic stimuli were different in their amplitude. Furthermore, the side of presynaptic stimulation that evoked larger Ca²⁺ transients depended on the location of the recorded dendritic regions. This result means that the spike‐triggered Ca²⁺ transients in dendrites depend on postsynaptic activity. It is proposed that Ca²⁺ entry through voltage‐dependent Ca²⁺ channels activated by the action potentials will be enhanced by excitatory synaptic inputs at the dendrites in the cricket giant interneurons. © 2002 Wiley Periodicals, Inc. J Neurobiol 50: 234–244, 2002; DOI 10.1002/neu.10032     

Dendritic action potentials of pyramidal tract neurons in the cat sensorimotor cortex

The intracellular activity of pyramidal tract neurons was studied during electrical stimulation of ventrolateral and ventroposterolateral thalamic nuclei in acute experiments on cats immobilized by myorelaxants. Somatic action potentials were observed and spontaneous spikes were also produced by single and rhythmic stimulation of the thalamic nuclei at the rate of 8–14 Hz, by iontophoretic application of strychnine, and by intracellular depolarizing current pulses. These potentials had a relatively low and variable amplitude of 5–60 mV and are presumed to be dendritic action potentials. It is postulated that these variable potentials arise in the dendrites of pyramidal neurons with multiple zones generating such activity. No interaction was observed where somatic and dendritic action potentials occur simultaneously. The possible functional role of dendritic action potentials is discussed.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 18, No. 4, pp. 435–443, July–August, 1986.     

Direction of action potential propagation influences calcium increases in distal dendrites of the cricket giant interneurons

To understand the relationship between the propagation direction of action potentials and dendritic Ca(2+) elevation, simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and intradendritic membrane potential were performed in the wind-sensitive giant interneurons of the cricket. The dendritic Ca(2+) transients induced by synaptically-evoked action potentials had larger amplitudes than those induced by backpropagating spikes evoked by antidromic stimulation. The amplitude of the [Ca(2+)](i) changes induced by antidromic stimuli combined with subthreshold synaptic stimulation was not different from that of the Ca(2+) increases evoked by the backpropagating spikes alone. This result means that the synaptically activated Ca(2+) release from intracellular stores does not contribute to enhancement of Ca(2+) elevation induced by backpropagating spikes. On the other hand, the synaptically evoked action potentials were also increased at distal dendrites in which the Ca(2+) elevation was enhanced. When the dendritic and axonal spikes were simultaneously recorded, the delay between dendritic spike and ascending axonal spike depended upon which side of the cercal nerves was stimulated. Further, dual intracellular recording at different dendritic branches illustrated that the dendritic spike at the branch arborizing on the stimulated side preceded the spike recorded at the other side of the dendrite. These results suggest that the spike-initiation site shifts depending on the location of the activated postsynaptic site. It is proposed that the difference of spike propagation manner could change the action potential waveform at the distal dendrite, and could produce synaptic activity-dependent Ca(2+) dynamics in the giant interneurons.     

Dendritic backpropagation and synaptic plasticity in the mormyrid electrosensory lobe

This study is concerned with the origin of backpropagating action potentials in GABAergic, medium ganglionic layer neurones (MG-cells) of the mormyrid electrosensory lobe (ELL). The characteristically broad action potentials of these neurones are required for the expression of spike timing dependent plasticity (STDP) at afferent parallel fibre synapses. It has been suggested that this involves active conductances in MG-cell apical dendrites, which constitute a major component of the ELL molecular layer. Immunohistochemistry showed dense labelling of voltage gated sodium channels (VGSC) throughout the molecular layer, as well as in the ganglionic layer containing MG somata, and in the plexiform and upper granule cell layers of ELL. Potassium channel labelling was sparse, being most abundant in the deep fibre layer and the nucleus of the electrosensory lobe.Intracellular recordings from MG-cells in vitro, made in conjunction with voltage sensitive dye measurements, confirmed that dendritic backpropagation is active over at least the inner half of the molecular layer. Focal TTX applications demonstrated that in most case the origin of the backpropagating action potentials is in the proximal dendrites, whereas the small narrow spikes also seen in these neurones most likely originate in the axon. It had been speculated that the slow time course of membrane repolarisation following the broad action potentials was due to a poor expression of potassium channels in the dendritic compartments, or to their voltage- or calcium-sensitive inactivation. However application of TEA and 4AP confirmed that both A-type and delayed rectifying potassium channels normally contribute to membrane repolarisation following dendritic and axonal spikes. An alternative explanation for the shape of MG action potentials is that they represent the summation of active events occurring more or less synchronously in distal dendrites.Coincidence of backpropagating action potentials with parallel fibre input produces a strong local depolarisation that could be sufficient to cause local secretion of GABA, which might then cause plastic change through an action on presynaptic GABA_B receptors. However, STP depression remained robust in the presence of GABAB receptor antagonists.     

Dendritic Spikes Amplify the Synaptic Signal to Enhance Detection of Motion in a Simulation of the Direction-Selective Ganglion Cell

The On-Off direction-selective ganglion cell (DSGC) in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials) are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS) in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell''s dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within cortical circuitry.     

Initiation of Sodium Spikelets in Basal Dendrites of Neocortical Pyramidal Neurons

Cortical information processing relies critically on the processing of electrical signals in pyramidal neurons. Electrical transients mainly arise when excitatory synaptic inputs impinge upon distal dendritic regions. To study the dendritic aspect of synaptic integration one must record electrical signals in distal dendrites. Since thin dendritic branches, such as oblique and basal dendrites, do not support routine glass electrode measurements, we turned our effort towards voltage-sensitive dye recordings. Using the optical imaging approach we found and reported previously that basal dendrites of neocortical pyramidal neurons show an elaborate repertoire of electrical signals, including backpropagating action potentials and glutamate-evoked plateau potentials. Here we report a novel form of electrical signal, qualitatively and quantitatively different from backpropagating action potentials and dendritic plateau potentials. Strong glutamatergic stimulation of an individual basal dendrite is capable of triggering a fast spike, which precedes the dendritic plateau potential. The amplitude of the fast initial spikelet was actually smaller that the amplitude of the backpropagating action potential in the same dendritic segment. Therefore, the fast initial spike was dubbed “spikelet”. Both the basal spikelet and plateau potential propagate decrementally towards the cell body, where they are reflected in the somatic whole-cell recordings. The low incidence of basal spikelets in the somatic intracellular recordings and the impact of basal spikelets on soma-axon action potential initiation are discussed.     

Electrical signaling in the olfactory bulb

The olfactory bulb employs lateral and feedback inhibitory pathways to distribute odor information across parallel assemblies of mitral and granule cells. The pathways involve dendritic action potentials that can interact with a variety of voltage-dependent conductances and synaptic transmission to produce complex and dynamic patterns of activity. Electrical coupling also helps to ensure proper coordination and synchronization of these patterns. These mechanisms provide numerous options for dynamic modulation and control of signaling in the olfactory bulb.     

The single administration of ethanol and the amplitude of the action potentials of the neocortical neurons in rats: extracellular studies]

On outbred rats the influence was studied of acute administration of moderate dozes of ethanol (150 mg--1.2 g/kg, intraperitoneally) on the motor cortex neurones. It was shown that ethanol in the range of these dozes led to a change of the amplitude of extracellularly recorded action potentials, which could be directed to an increase or decrease. In the used range minimum as well as maximum dozes in various animals might elicit contrary effects, i.e. no dependence was observed of the direction of reaction of the studied neurones on the administrated doze. Possible mechanisms are discussed which may be the basis of the change of the amplitude of extracellular action potentials. Conclusion is made that use of moderate dozes of ethanol is a useful condition for studies directed to a search of mechanisms of initial reaction to alcohol action.     

Intrinsic and extrinsic determinants of ion channel localization in neurons

Neurons are an extremely diverse group of excitable cells with a wide variety of morphologies including complex dendritic trees and very long axons. The electrical properties of neurons depend not only on the types of ion channels and receptors expressed, but also on where these channels are located in the cell. Two extreme examples that illustrate the subcellular polarized nature of neurons and the tight regulation of ion channel localization can be seen at the axon initial segment and the node of Ranvier. The axon initial segment is important for initiation of action potentials in the axon, whereas the node of Ranvier is required for the rapid, faithful and efficient propagation of action potentials along the axon. Given the similarity of their functions it is not surprising that nearly every protein component of the axon initial segment is also found at the node. However, there is one very important difference between these two sites: nodes require extrinsic, glial-derived factors in order to form, whereas the axon initial segment is intrinsically determined by the neuron. This mini-review discusses recent results that have begun to clarify the intrinsic and extrinsic mechanisms underlying formation of nodes and axon initial segments, and poses several important unanswered questions regarding their unique mechanisms of formation.     

The neuronal basis of a sensory analyser, the acridid movement detector system. II. response decrement, convergence, and the nature of the excitatory afferents to the fan-like dendrites of the LGMD.

No dendritic spikes occur in the input fan of the lobular giant movement detector (LGMD) neurone. The action potentials are initiated at the point of thickening of the axon, which therefore represents the site of convergence of the retinotopic projection in the MD system. Previous work has shown that the site of decrement in response to repetitive visual stimulation is distal to this point. No change in spiking threshold in the LGMD could be demonstrated, and decrement in the number of LGMD action potentials is completely explained by the observed decrement of EPSPs recorded in the LGMD input dendritic fan. Possible postsynaptic mechanisms which might affect EPSP amplitude are excluded experimentally or shown to be improbable. Latency measurements during electrical stimulation in the second chiasma (which produces a decrementing EPSP in the fan) indicate that the pathway from the chiasma afferents to the LGMD fan is probably monosynaptic. By exclusion, the site of decrement appears to be located at the presynaptic terminal of that synapse. Generalization of habituation of the response to ON and OFF stimuli is demonstrated, showing that the presynaptic neurone at the labile synapse is an ON/OFF unit. The greater part of the previously described sensitivity gradient on the retina, relative to the MD response, appears to be explicable by the geometry of the LGMD fan and of the retinotopic projection. We conclude that the LGMD is fed by a homogeneous population of ON/OFF units running in the second optic chiasma, which form labile synapses on the input fan.     

Dynamics of Intrinsic Dendritic Calcium Signaling during Tonic Firing of Thalamic Reticular Neurons

The GABAergic neurons of the nucleus reticularis thalami that control the communication between thalamus and cortex are interconnected not only through axo-dendritic synapses but also through gap junctions and dendro-dendritic synapses. It is still unknown whether these dendritic communication processes may be triggered both by the tonic and the T-type Ca²⁺ channel-dependent high frequency burst firing of action potentials displayed by nucleus reticularis neurons during wakefulness and sleep, respectively. Indeed, while it is known that activation of T-type Ca²⁺ channels actively propagates throughout the dendritic tree, it is still unclear whether tonic action potential firing can also invade the dendritic arborization. Here, using two-photon microscopy, we demonstrated that dendritic Ca²⁺ responses following somatically evoked action potentials that mimic wake-related tonic firing are detected throughout the dendritic arborization. Calcium influx temporally summates to produce dendritic Ca²⁺ accumulations that are linearly related to the duration of the action potential trains. Increasing the firing frequency facilitates Ca²⁺ influx in the proximal but not in the distal dendritic compartments suggesting that the dendritic arborization acts as a low-pass filter in respect to the back-propagating action potentials. In the more distal compartment of the dendritic tree, T-type Ca²⁺ channels play a crucial role in the action potential triggered Ca²⁺ influx suggesting that this Ca²⁺ influx may be controlled by slight changes in the local dendritic membrane potential that determine the T-type channels’ availability. We conclude that by mediating Ca²⁺ dynamic in the whole dendritic arborization, both tonic and burst firing of the nucleus reticularis thalami neurons might control their dendro-dendritic and electrical communications.     

Cav1.2 calcium channels modulate the spiking pattern of hippocampal pyramidal cells

Ca(v)1.2 L-type calcium channels support hippocampal synaptic plasticity, likely by facilitating dendritic Ca2+ influx evoked by action potentials (AP) back-propagated from the soma. Ca2+ influx into hippocampal neurons during somatic APs is sufficient to activate signalling pathways associated with late phase LTP. Thus, mechanisms controlling AP firing of hippocampal neurons are of major functional relevance. We examined the excitability of CA1 pyramidal cells using somatic current-clamp recordings in brain slices from control type mice and mice with the Ca(v)1.2 gene inactivated in principal hippocampal neurons. Lack of the Ca(v)1.2 protein did not affect either affect basic characteristics, such as resting membrane potential and input resistance, or parameters of single action potentials (AP) induced by 5 ms depolarising current pulses. However, CA1 hippocampal neurons from control and mutant mice differed in their patterns of AP firing during 500 ms depolarising current pulses: threshold voltage for repetitive firing was shifted significantly by about 5 mV to more depolarised potentials in the mutant mice (p<0.01), and the latency until firing of the first AP was prolonged (73.2+/-6.6 ms versus 48.1+/- 7.8 ms in control; p<0.05). CA1 pyramidal cells from the mutant mice also showed a lowered initial spiking frequency within an AP train. In control cells, isradipine had matching effects, while BayK 8644 facilitated spiking. Our data demonstrate that Ca(v)1.2 channels are involved in regulating the intrinsic excitability of CA1 pyramidal neurons. This cellular mechanism may contribute to the known function of Ca(v)1.2 channels in supporting synaptic plasticity and memory.     

A cooperative switch determines the sign of synaptic plasticity in distal dendrites of neocortical pyramidal neurons

Pyramidal neurons in the cerebral cortex span multiple cortical layers. How the excitable properties of pyramidal neuron dendrites allow these neurons to both integrate activity and store associations between different layers is not well understood, but is thought to rely in part on dendritic backpropagation of action potentials. Here we demonstrate that the sign of synaptic plasticity in neocortical pyramidal neurons is regulated by the spread of the backpropagating action potential to the synapse. This creates a progressive gradient between LTP and LTD as the distance of the synaptic contacts from the soma increases. At distal synapses, cooperative synaptic input or dendritic depolarization can switch plasticity between LTD and LTP by boosting backpropagation of action potentials. This activity-dependent switch provides a mechanism for associative learning across different neocortical layers that process distinct types of information.     

Electrical advantages of dendritic spines

Many neurons receive excitatory glutamatergic input almost exclusively onto dendritic spines. In the absence of spines, the amplitudes and kinetics of excitatory postsynaptic potentials (EPSPs) at the site of synaptic input are highly variable and depend on dendritic location. We hypothesized that dendritic spines standardize the local geometry at the site of synaptic input, thereby reducing location-dependent variability of local EPSP properties. We tested this hypothesis using computational models of simplified and morphologically realistic spiny neurons that allow direct comparison of EPSPs generated on spine heads with EPSPs generated on dendritic shafts at the same dendritic locations. In all morphologies tested, spines greatly reduced location-dependent variability of local EPSP amplitude and kinetics, while having minimal impact on EPSPs measured at the soma. Spine-dependent standardization of local EPSP properties persisted across a range of physiologically relevant spine neck resistances, and in models with variable neck resistances. By reducing the variability of local EPSPs, spines standardized synaptic activation of NMDA receptors and voltage-gated calcium channels. Furthermore, spines enhanced activation of NMDA receptors and facilitated the generation of NMDA spikes and axonal action potentials in response to synaptic input. Finally, we show that dynamic regulation of spine neck geometry can preserve local EPSP properties following plasticity-driven changes in synaptic strength, but is inefficient in modifying the amplitude of EPSPs in other cellular compartments. These observations suggest that one function of dendritic spines is to standardize local EPSP properties throughout the dendritic tree, thereby allowing neurons to use similar voltage-sensitive postsynaptic mechanisms at all dendritic locations.     

Peptidergic transmission in the brain. III. Hippocampal inhibition by the amygdala.

The mechanism of arginine vasopressin (AVP) action in the rat hippocampus has been determined. The peptide activates inhibitory interneurons and constricts cerebral microvessels. In the whole animal, each of these direct actions has secondary consequences for the excitability of pyramidal cells. Recent studies have shown that a peptide similar to AVP mediates endogenous neurotransmission in the hippocampus. Here we report experiments showing that the endogenous peptide activates the same mechanisms as exogenously applied AVP. The endogenous AVP-like peptide has no effect on the presynaptic fiber volley, or on pure somatic and dendritic postsynaptic potentials. These results are taken to exclude presynaptic mechanisms as explanations for the peptide's action. The endogenously released peptide inhibits individual pyramidal cells in single unit recording and excites presumed interneurons, just as AVP itself is known to act. The endogenous peptide is released only by stimuli applied to a nucleus that contains immunoreactive AVP and projects to the hippocampus.     

Models of neocortical layer 5b pyramidal cells capturing a wide range of dendritic and perisomatic active properties

The thick-tufted layer 5b pyramidal cell extends its dendritic tree to all six layers of the mammalian neocortex and serves as a major building block for the cortical column. L5b pyramidal cells have been the subject of extensive experimental and modeling studies, yet conductance-based models of these cells that faithfully reproduce both their perisomatic Na(+)-spiking behavior as well as key dendritic active properties, including Ca(2+) spikes and back-propagating action potentials, are still lacking. Based on a large body of experimental recordings from both the soma and dendrites of L5b pyramidal cells in adult rats, we characterized key features of the somatic and dendritic firing and quantified their statistics. We used these features to constrain the density of a set of ion channels over the soma and dendritic surface via multi-objective optimization with an evolutionary algorithm, thus generating a set of detailed conductance-based models that faithfully replicate the back-propagating action potential activated Ca(2+) spike firing and the perisomatic firing response to current steps, as well as the experimental variability of the properties. Furthermore, we show a useful way to analyze model parameters with our sets of models, which enabled us to identify some of the mechanisms responsible for the dynamic properties of L5b pyramidal cells as well as mechanisms that are sensitive to morphological changes. This automated framework can be used to develop a database of faithful models for other neuron types. The models we present provide several experimentally-testable predictions and can serve as a powerful tool for theoretical investigations of the contribution of single-cell dynamics to network activity and its computational capabilities.     

Unique roles of SK and Kv4.2 potassium channels in dendritic integration

Focal activation of glutamate receptors in distal dendrites of hippocampal pyramidal cells triggers voltage-dependent Ca(2+) channel-mediated plateau potentials that are confined to the stimulated dendrite. We examined the role of dendritic K(+) conductances in determining the amplitude, duration, and spatial compartmentalization of plateau potentials. Manipulations that blocked SK-type Ca(2+)-activated K(+) channels, including apamin and BAPTA dialysis, increased the duration of plateau potentials without affecting their amplitude or compartmentalization. Manipulations that blocked Kv4.2 A-type K(+) channels, including a dominant-negative Kv4.2 construct and 4-aminopyridine, increased the amplitude of plateau potentials by allowing them to recruit neighboring dendrites. Prolongation of plateau potentials or block of Kv4.2 channels at branch points facilitated the ability of dendritic excitation to trigger fast action potentials. SK channels thus underlie repolarization of dendritic plateau potentials, whereas Kv4.2 channels confine these potentials to single dendritic branches, and both act in concert to regulate synaptic integration.