Mechanisms Underlying Burst and Regular Spiking Evoked by Dendritic Depolarization in Layer 5 Cortical Pyramidal Neurons

1999 ◽  
Vol 81 (3) ◽  
pp. 1341-1354 ◽  
Author(s):  
Peter Schwindt ◽  
Wayne Crill
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Critical Level ◽  
Pyramidal Cells ◽  
Burst Firing ◽  
Action Current ◽  
Constant Frequency ◽  
Functional Implications ◽  
Cortical Pyramidal Neurons ◽  
Apical Dendrites

Mechanisms underlying burst and regular spiking evoked by dendritic depolarization in layer 5 cortical pyramidal neurons. Apical dendrites of layer 5 pyramidal cells in a slice preparation of rat sensorimotor cortex were depolarized focally by long-lasting glutamate iontophoresis while recording intracellularly from their soma. In most cells the firing pattern evoked by the smallest dendritic depolarization that evoked spikes consisted of repetitive bursts of action potentials. During larger dendritic depolarizations initial burst firing was followed by regular spiking. As dendritic depolarization was increased further the duration (but not the firing rate) of the regular spiking increased, and the duration of burst firing decreased. Depolarization of the soma in most of the same cells evoked only regular spiking. When the dendrite was depolarized to a critical level below spike threshold, intrasomatic current pulses or excitatory postsynaptic potentials also triggered bursts instead of single spikes. The bursts were driven by a delayed depolarization (DD) that was triggered in an all-or-none manner along with the first Na+ spike of the burst. Somatic voltage-clamp experiments indicated that the action current underlying the DD was generated in the dendrite and was Ca2+ dependent. Thus the burst firing was caused by a Na+ spike-linked dendritic Ca2+spike, a mechanism that was available only when the dendrite was adequately depolarized. Larger dendritic depolarization that evoked late, constant-frequency regular spiking also evoked a long-lasting, Ca2+-dependent action potential (a “plateau”). The duration of the plateau but not its amplitude was increased by stronger dendritic depolarization. Burst-generating dendritic Ca2+spikes could not be elicited during this plateau. Thus plateau initiation was responsible for the termination of burst firing and the generation of the constant-frequency regular spiking. We conclude that somatic and dendritic depolarization can elicit quite different firing patterns in the same pyramidal neuron. The burst and regular spiking observed during dendritic depolarization are caused by two types of Ca2+-dependent dendritic action potentials. We discuss some functional implications of these observations.

Differential Cholinergic Modulation of Ca2+ Transients Evoked by Backpropagating Action Potentials in Apical and Basal Dendrites of Cortical Pyramidal Neurons

2008 ◽  
Vol 99 (6) ◽  
pp. 2833-2843 ◽  
Author(s):  
Kwang-Hyun Cho ◽  
Hyun-Jong Jang ◽  
Eun-Hui Lee ◽  
Shin Hee Yoon ◽  
Sang June Hahn ◽  
...  
Keyword(s):  
High Frequency ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Channel Blocker ◽  
Dependent Manner ◽  
Type K ◽  
Basal Dendrites ◽  
Cortical Pyramidal Neurons ◽  
Apical Dendrites ◽  
Whole Cell Recordings

The effect of the cholinergic agonist carbachol (CCh) on backpropagating action potential (bAP)–evoked Ca2+ transients in distal apical and basal dendrites of layer 2/3 pyramidal neurons in the primary visual cortex of rats was studied using whole cell recordings and confocal Ca2+ imaging. In the presence of CCh (20 μM), initial bAP-evoked Ca2+ transients were followed by large propagating secondary Ca2+ transients that were restricted to proximal apical dendrites ≤40 μm from the soma. In middle apical dendrites (41–100 μm from the soma), Ca2+ transients evoked by AP bursts at 20 Hz, but not by single APs, were increased by CCh without secondary transients. CCh failed to increase the bAP-evoked Ca2+ transients in distal apical dendrites (101–270 μm from the soma). In contrast, in basal dendrites, CCh increased Ca2+ transients evoked by AP bursts, but not by single APs, and these transients were relatively constant over the entire length of the dendrites. CCh further increased the enhanced bAP-evoked Ca2+ transients in the presence of 4-aminopyridine (200 μM), an A-type K+ channel blocker, in basal and apical dendrites, except in distal apical dendrites. CCh increased large Ca2+ transients evoked by high-frequency AP bursts in basal dendrites, but not in distal apical dendrites. CCh-induced increase in Ca2+ transients was mediated by InsP3-dependent Ca2+-induced Ca2+-release. These results suggest that cholinergic stimulation differentially increases the bAP-evoked increase in [Ca2+]i in apical and basal dendrites, which may modulate synaptic activities in a location-dependent manner.

scholarly journals Spikelets in pyramidal neurons: generating mechanisms, distinguishing properties, and functional implications

2019 ◽  
Vol 31 (1) ◽  
pp. 101-119 ◽  
Author(s):  
Martina Michalikova ◽  
Michiel W.H. Remme ◽  
Dietmar Schmitz ◽  
Susanne Schreiber ◽  
Richard Kempter
Keyword(s):  
Single Cell ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Functional Implications ◽  
Cortical Pyramidal Neurons ◽  
Dendritic Spikes ◽  
Experimental Findings ◽  
Small Spike ◽  
Ephaptic Coupling ◽  
Neuronal Compartments

Abstract Spikelets are small spike-like depolarizations that are found in somatic recordings of many neuron types. Spikelets have been assigned important functions, ranging from neuronal synchronization to the regulation of synaptic plasticity, which are specific to the particular mechanism of spikelet generation. As spikelets reflect spiking activity in neuronal compartments that are electrotonically distinct from the soma, four modes of spikelet generation can be envisaged: (1) dendritic spikes or (2) axonal action potentials occurring in a single cell as well as action potentials transmitted via (3) gap junctions or (4) ephaptic coupling in pairs of neurons. In one of the best studied neuron type, cortical pyramidal neurons, the origins and functions of spikelets are still unresolved; all four potential mechanisms have been proposed, but the experimental evidence remains ambiguous. Here we attempt to reconcile the scattered experimental findings in a coherent theoretical framework. We review in detail the various mechanisms that can give rise to spikelets. For each mechanism, we present the biophysical underpinnings as well as the resulting properties of spikelets and compare these predictions to experimental data from pyramidal neurons. We also discuss the functional implications of each mechanism. On the example of pyramidal neurons, we illustrate that several independent spikelet-generating mechanisms fulfilling vastly different functions might be operating in a single cell.

scholarly journals Apical length governs computational diversity of L5 pyramidal neurons

2019 ◽  
Author(s):  
Alessandro R. Galloni ◽  
Aeron Laffere ◽  
Ede Rancz
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Apical Dendrite ◽  
Common Assumption ◽  
Dendritic Excitability ◽  
Visual Cortices ◽  
The Common ◽  
Channel Dependent ◽  
Apical Dendrites ◽  
The Brain

AbstractAnatomical similarity across the neocortex has led to the common assumption that the circuitry is modular and performs stereotyped computations. Layer 5 pyramidal neurons (L5PNs) in particular are thought to be central to cortical computation because of their extensive arborisation and nonlinear dendritic operations. Here, we demonstrate that computations associated with dendritic Ca2+ plateaus in L5PNs vary substantially between the primary and secondary visual cortices. L5PNs in the secondary visual cortex show reduced dendritic excitability and smaller propensity for burst firing. This reduced excitability is correlated with shorter apical dendrites. Using numerical modelling, we uncover a universal principle underlying the influence of apical length on dendritic backpropagation and excitability, based on a Na+ channel-dependent broadening of backpropagating action potentials. In summary, we provide new insights into the modulation of dendritic excitability by apical dendrite length and show that the operational repertoire of L5 neurons is not universal throughout the brain.

scholarly journals Bayesian modeling of BAC firing as a mechanism for apical amplification in neocortical pyramidal neurons

2019 ◽  
Author(s):  
Jim W. Kay ◽  
W. A. Phillips ◽  
Jaan Aru ◽  
Bruce P. Graham ◽  
Matthew E. Larkum
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Single Site ◽  
Biophysical Model ◽  
Cellular Mechanisms ◽  
Context Sensitive ◽  
Dendritic Shaft ◽  
Current Task ◽  
Integration Sites

AbstractPyramidal cells in layer 5 of the neocortex have two distinct integration sites. These cells integrate inputs to basal dendrites in the soma while integrating inputs to the tuft in a site at the top of the apical trunk. The two sites communicate by action potentials that backpropagate to the apical site and by backpropagation-activated calcium spikes (BAC firing) that travel from the apical to the somatic site. Six key messages arise from the probabilistic information-theoretic analyses of BAC firing presented here. First, we suggest that pyramidal neurons with BAC firing could convert the odds in favour of the presence of a feature given the basal data into the odds in favour of the presence of a feature given the basal data and the apical input, by a simple Bayesian calculation. Second, the strength of the cell’s response to basal input can be amplified when relevant to the current context, as specified by the apical input, without corrupting the message that it sends. Third, these analyses show rigorously how this apical amplification depends upon communication between the sites. Fourth, we use data on action potentials from a very detailed multi-compartmental biophysical model to study our general model in a more realistic setting, and demonstrate that it describes the data well. Fifth, this form of BAC firing meets criteria for distinguishing modulatory from driving interactions that have been specified using recent definitions of multivariate mutual information. Sixth, our general decomposition can be extended to cases where, instead of being purely driving or purely amplifying, apical and basal inputs can be partly driving and partly amplifying to various extents. These conclusions imply that an advance beyond the assumption of a single site of integration within pyramidal cells is needed, and suggest that the evolutionary success of neocortex may depend upon the cellular mechanisms of context-sensitive selective amplification hypothesized here.Author summaryThe cerebral cortex has a key role in conscious perception, thought, and action, and is predominantly composed of a particular kind of neuron: the pyramidal cells. The distinct shape of the pyramidal neuron with a long dendritic shaft separating two regions of profuse dendrites allows them to integrate inputs to the two regions separately and combine the results non-linearly to produce output. Here we show how inputs to this more distant site strengthen the cell’s output when it is relevant to the current task and environment. By showing that such neurons have capabilities that transcend those of neurons with the single site of integration assumed by many neuroscientists, this ‘splitting of the neuronal atom’ offers a radically new viewpoint from which to understand the evolution of the cortex and some of its many pathologies. This also suggests that approaches to artificial intelligence using neural networks might come closer to something analogous to real intelligence, if, instead of basing them on processing elements with a single site of integration, they were based on elements with two sites, as in cortex.

scholarly journals Evidence of calcium-permeable AMPA receptors in dendritic spines of CA1 pyramidal neurons

2014 ◽  
Vol 112 (2) ◽  
pp. 263-275 ◽  
Author(s):  
Hayley A. Mattison ◽  
Ashish A. Bagal ◽  
Michael Mohammadi ◽  
Nisha S. Pulimood ◽  
Christian G. Reich ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Calcium Influx ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Stratum Radiatum ◽  
Acute Hippocampal Slices ◽  
Cultured Slices ◽  
Apical Dendrites

GluA2-lacking, calcium-permeable α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) have unique properties, but their presence at excitatory synapses in pyramidal cells is controversial. We have tested certain predictions of the model that such receptors are present in CA1 cells and show here that the polyamine spermine, but not philanthotoxin, causes use-dependent inhibition of synaptically evoked excitatory responses in stratum radiatum, but not s. oriens, in cultured and acute hippocampal slices. Stimulation of single dendritic spines by photolytic release of caged glutamate induced an N-methyl-d-aspartate receptor-independent, use- and spermine-sensitive calcium influx only at apical spines in cultured slices. Bath application of glutamate also triggered a spermine-sensitive influx of cobalt into CA1 cell dendrites in s. radiatum. Responses of single apical, but not basal, spines to photostimulation displayed prominent paired-pulse facilitation (PPF) consistent with use-dependent relief of cytoplasmic polyamine block. Responses at apical dendrites were diminished, and PPF was increased, by spermine. Intracellular application of pep2m, which inhibits recycling of GluA2-containing AMPARs, reduced apical spine responses and increased PPF. We conclude that some calcium-permeable, polyamine-sensitive AMPARs, perhaps lacking GluA2 subunits, are present at synapses on apical dendrites of CA1 pyramidal cells, which may allow distinct forms of synaptic plasticity and computation at different sets of excitatory inputs.

Relationships Between Intracellular Calcium and Afterhyperpolarizations in Neocortical Pyramidal Neurons

2004 ◽  
Vol 91 (1) ◽  
pp. 324-335 ◽  
Author(s):  
H. J. Abel ◽  
J.C.F. Lee ◽  
J. C. Callaway ◽  
R. C. Foehring
Keyword(s):  
Intracellular Calcium ◽  
Linear Relationship ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Firing Frequency ◽  
Discharge Activity ◽  
Apical Dendrites ◽  
Neocortical Pyramidal Neurons

We examined the effects of recent discharge activity on [Ca2+]i in neocortical pyramidal cells. Our data confirm and extend the observation that there is a linear relationship between plateau [Ca2+]i and firing frequency in soma and proximal apical dendrites. The rise in [Ca2+] activates K+ channels underlying the afterhyperpolarization (AHP), which consists of 2 Ca2+-dependent components: the medium AHP (mAHP) and the slow AHP (sAHP). The mAHP is blocked by apamin, indicating involvement of SK-type Ca2+-dependent K+ channels. The identity of the apamin-insensitive sAHP channel is unknown. We compared the sAHP and the mAHP with regard to: 1) number and frequency of spikes versus AHP amplitude; 2) number and frequency of spikes versus [Ca2+]i; 3) IAHP versus [Ca2+]i. Our data suggest that sAHP channels require an elevation of [Ca2+]i in the cytoplasm, rather than at the membrane, consistent with a role for a cytoplasmic intermediate between Ca2+ and the K+ channels. The mAHP channels appear to respond to a restricted Ca2+ domain.

Axon terminal hyperexcitability associated with epileptogenesis in vitro. I. Origin of ectopic spikes

1993 ◽  
Vol 70 (3) ◽  
pp. 961-975 ◽  
Author(s):  
S. F. Stasheff ◽  
M. Hines ◽  
W. A. Wilson
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Model Neuron ◽  
Extracellular Recording ◽  
Pyramidal Cells ◽  
Initiation Site ◽  
Electrographic Seizures ◽  
Ca3 Pyramidal Cells

1. Intracellular and extracellular recording techniques were used to study the increase in ectopic (i.e., nonsomatic) action-potential generation occurring among CA3 pyramidal cells during the kindling-like induction of electrographic seizures (EGSs) in this subpopulation of the hippocampal slice. Kindling-like stimulus trains (60 Hz, 2 s) were delivered to s. radiatum of CA3 at 10-min intervals. As EGSs developed, the frequency of ectopic firing increased markedly (by 10.33 +/- 3.29 spikes/min, mean +/- SE, P << 0.01). Several methods were applied to determine the initiation site for these action potentials within the cell (axons vs. dendrites). 2. Collision tests were conducted between known antidromic and orthodromic action potentials in CA3 cells to determine the critical period, c, for collision. Attempts were then made to collide ectopic spikes with known antidromic action potentials. At intervals less than c, ectopic spikes failed to collide with antidromic ones, in 5 of 10 cases. In these cells, this clearly indicates that the ectopic spikes were themselves of axonal origin. In the remaining five cases, ectopic spikes collided with antidromic action potentials at intervals approximately equal to c, most likely because of interactions within the complex system of recurrent axon collaterals in CA3. 3. Action potentials of CA3 pyramidal cells were simulated with the use of a compartmental computer model, NEURON. These simulations were based on prior models of CA3 pyramidal neurons and of the motoneuron action potential. Simulated action potentials generated in axonal compartments possessed a prominent inflection on their rising phase (IS-SD break), which was difficult to appreciate in those spikes generated in somatic or dendritic compartments. 4. An analysis of action potentials recorded experimentally from CA3 pyramidal cells also showed that antidromic spikes possess a prominent IS-SD break that is not present in orthodromic spikes. In addition to identified antidromic action potentials, ectopic spikes also possess such an inflection. Together with the predictions of computer simulations, this analysis also indicates that ectopic spikes originate in the axons of CA3 cells. 5. Tetrodotoxin (TTX, 50 microM) was locally applied by pressure injection while monitoring ectopic spike activity. Localized application of TTX to regions of the slice that could include the axons but not the dendrites of recorded cells abolished or markedly reduced the frequency of ectopic spikes (n = 5), further confirming the hypothesis that these action potentials arise from CA3 axons.(ABSTRACT TRUNCATED AT 400 WORDS)

Fiberoptic System for Recording Dendritic Calcium Signals in Layer 5 Neocortical Pyramidal Cells in Freely Moving Rats

2007 ◽  
Vol 98 (3) ◽  
pp. 1791-1805 ◽  
Author(s):  
Masanori Murayama ◽  
Enrique Pérez-Garci ◽  
Hans-Rudolf Lüscher ◽  
Matthew E. Larkum
Keyword(s):  
Pyramidal Neurons ◽  
Calcium Influx ◽  
Signal To Noise Ratio ◽  
Pyramidal Cells ◽  
Cellular Mechanisms ◽  
Novel Approach ◽  
Specific Loading ◽  
Apical Dendrites

Calcium influx into the dendritic tufts of layer 5 neocortical pyramidal neurons modifies a number of important cellular mechanisms. It can trigger local synaptic plasticity and switch the firing properties from regular to burst firing. Due to methodological limitations, our knowledge about Ca2+ spikes in the dendritic tuft stems mostly from in vitro experiments. However, it has been speculated that regenerative Ca2+ events in the distal dendrites correlate with distinct behavioral states. Therefore it would be most desirable to be able to record these Ca2+ events in vivo, preferably in the behaving animal. Here, we present a novel approach for recording Ca2+ signals in the dendrites of populations of layer 5 pyramidal neurons in vivo, which ensures that all recorded fluorescence changes are due to intracellular Ca2+ signals in the apical dendrites. The method has two main features: 1) bolus loading of layer 5 with a membrane-permeant Ca2+ dye resulting in specific loading of pyramidal cell dendrites in the upper layers and 2) a fiberoptic cable attached to a gradient index lens and a prism reflecting light horizontally at 90° to the angle of the apical dendrites. We demonstrate that the in vivo signal-to-noise ratio recorded with this relatively inexpensive and easy-to-implement fiberoptic-based device is comparable to conventional camera-based imaging systems used in vitro. In addition, the device is flexible and lightweight and can be used for recording Ca2+ signals in the distal dendritic tuft of freely behaving animals.

Calcium Coding and Adaptive Temporal Computation in Cortical Pyramidal Neurons

1998 ◽  
Vol 79 (3) ◽  
pp. 1549-1566 ◽  
Author(s):  
Xiao-Jing Wang
Keyword(s):  
Current Pulse ◽  
Pyramidal Neurons ◽  
Model Neuron ◽  
Pyramidal Cells ◽  
Spike Frequency ◽  
Neuronal Firing ◽  
Spike Frequency Adaptation ◽  
Synaptic Inputs ◽  
Cortical Pyramidal Neurons ◽  
Intracellular Ca

Wang, Xiao-Jing. Calcium coding and adaptive temporal computation in cortical pyramidal neurons. J. Neurophysiol. 79: 1549–1566, 1998. In this work, we present a quantitative theory of temporal spike-frequency adaptation in cortical pyramidal cells. Our model pyramidal neuron has two-compartments (a “soma” and a “dendrite”) with a voltage-gated Ca2+ conductance ( g Ca) and a Ca2+-dependent K+ conductance ( g AHP) located at the dendrite or at both compartments. Its frequency-current relations are comparable with data from cortical pyramidal cells, and the properties of spike-evoked intracellular [Ca2+] transients are matched with recent dendritic [Ca2+] imaging measurements. Spike-frequency adaptation in response to a current pulse is characterized by an adaptation time constant τadap and percentage adaptation of spike frequency F adap [% (peak − steady state)/peak]. We show how τadap and F adap can be derived in terms of the biophysical parameters of the neural membrane and [Ca2+] dynamics. Two simple, experimentally testable, relations between τadap and F adap are predicted. The dependence of τadap and F adap on current pulse intensity, electrotonic coupling between the two compartments, g AHP as well the [Ca2+] decay time constant τCa, is assessed quantitatively. In addition, we demonstrate that the intracellular [Ca2+] signal can encode the instantaneous neuronal firing rate and that the conductance-based model can be reduced to a simple calcium-model of neuronal activity that faithfully predicts the neuronal firing output even when the input varies relatively rapidly in time (tens to hundreds of milliseconds). Extensive simulations have been carried out for the model neuron with random excitatory synaptic inputs mimicked by a Poisson process. Our findings include 1) the instantaneous firing frequency (averaged over trials) shows strong adaptation similar to the case with current pulses; 2) when the g AHP is blocked, the dendritic g Ca could produce a hysteresis phenomenon where the neuron is driven to switch randomly between a quiescent state and a repetitive firing state. The firing pattern is very irregular with a large coefficient of variation of the interspike intervals (ISI CV > 1). The ISI distribution shows a long tail but is not bimodal. 3) By contrast, in an intrinsically bursting regime (with different parameter values), the model neuron displays a random temporal mixture of single action potentials and brief bursts of spikes. Its ISI distribution is often bimodal and its power spectrum has a peak. 4) The spike-adapting current I AHP, as delayed inhibition through intracellular Ca2+ accumulation, generates a “forward masking” effect, where a masking input dramatically reduces or completely suppresses the neuronal response to a subsequent test input. When two inputs are presented repetitively in time, this mechanism greatly enhances the ratio of the responses to the stronger and weaker inputs, fulfilling a cellular form of lateral inhibition in time. 5) The [Ca2+]-dependent I AHP provides a mechanism by which the neuron unceasingly adapts to the stochastic synaptic inputs, even in the stationary state following the input onset. This creates strong negative correlations between output ISIs in a frequency-dependent manner, while the Poisson input is totally uncorrelated in time. Possible functional implications of these results are discussed.

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