Persistent Na+ Current Modifies Burst Discharge By Regulating Conditional Backpropagation of Dendritic Spikes

The estimation and detection of stimuli by sensory neurons is affected by factors that govern a transition from tonic to burst mode and the frequency chracteristics of burst output. Pyramidal cells in the electrosensory lobe of weakly electric fish generate spike bursts for the purpose of stimulus detection. Spike bursts are generated during repetitive discharge when a frequency-dependent broadening of dendritic spikes increases current flow from dendrite to soma to potentiate a somatic depolarizing afterpotential (DAP). The DAP eventually triggers a somatic spike doublet with an interspike interval that falls inside the dendritic refractory period, blocking spike backpropagiation and the DAP. Repetition of this process gives rise to a rhythmic dendritic spike failure, termed conditional backpropagation, that converts cell output from tonic to burst discharge. Through in vitrorecordings and compartmental modeling we show that burst frequency is regulated by the rate of DAP potentiation during a burst, which determines the time required to discharge the spike doublet that blocks backpropagation. DAP potentiation is maginfied through a postitve feedback process when an increase in dendritic spike duration activates persistent sodium current ( I NaP). I NaP further promotes a slow depolarization that induces a shift from tonic to burst discharge over time. The results are consistent with a dynamical systems analysis that shows that the threshold separating tonic and burst discharge can be represented as a saddle-node bifurcation. The interaction between dendritic K+ current and I NaP provides a physiological explanation for a variable time scale of bursting dynamics characteristic of such a bifurcation.

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Model of Gamma Frequency Burst Discharge Generated by Conditional Backpropagation

Journal of Neurophysiology ◽

10.1152/jn.2001.86.4.1523 ◽

2001 ◽

Vol 86 (4) ◽

pp. 1523-1545 ◽

Cited By ~ 41

Author(s):

Brent Doiron ◽

André Longtin ◽

Ray W. Turner ◽

Leonard Maler

Keyword(s):

Potassium Channels ◽

Action Potential ◽

Refractory Period ◽

Core Model ◽

Burst Discharge ◽

The Core ◽

Dendritic Spikes ◽

Dendritic Spike ◽

Frequency Burst ◽

Spike Bursts

Pyramidal cells of the electrosensory lateral line lobe (ELL) of the weakly electric fish Apteronotus leptorhynchus have been shown to produce oscillatory burst discharge in the γ-frequency range (20–80 Hz) in response to constant depolarizing stimuli. Previous in vitro studies have shown that these bursts arise through a recurring spike backpropagation from soma to apical dendrites that is conditional on the frequency of action potential discharge (“conditional backpropagation”). Spike bursts are characterized by a progressive decrease in inter-spike intervals (ISIs), and an increase of dendritic spike duration and the amplitude of a somatic depolarizing afterpotential (DAP). The bursts are terminated when a high-frequency somatic spike doublet exceeds the dendritic spike refractory period, preventing spike backpropagation. We present a detailed multi-compartmental model of an ELL basilar pyramidal cell to simulate somatic and dendritic spike discharge and test the conditions necessary to produce a burst output. The model ionic channels are described by modified Hodgkin-Huxley equations and distributed over both soma and dendrites under the constraint of available immunocytochemical and electrophysiological data. The currents modeled are somatic and dendritic sodium and potassium involved in action potential generation, somatic and proximal apical dendritic persistent sodium, and KV3.3 and fast transient A-like potassium channels distributed over the entire model cell. The core model produces realistic somatic and dendritic spikes, differential spike refractory periods, and a somatic DAP. However, the core model does not produce oscillatory spike bursts with constant depolarizing stimuli. We find that a cumulative inactivation of potassium channels underlying dendritic spike repolarization is a necessary condition for the model to produce a sustained γ-frequency burst pattern matching experimental results. This cumulative inactivation accounts for a frequency-dependent broadening of dendritic spikes and results in a conditional failure of backpropagation when the intraburst ISI exceeds dendritic spike refractory period, terminating the burst. These findings implicate ion channels involved in repolarizing dendritic spikes as being central to the process of conditional backpropagation and oscillatory burst discharge in this principal sensory output neuron of the ELL.

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Dendritic Na+ Current Inactivation Can Increase Cell Excitability By Delaying a Somatic Depolarizing Afterpotential

Journal of Neurophysiology ◽

10.1152/jn.00653.2005 ◽

2005 ◽

Vol 94 (6) ◽

pp. 3836-3848 ◽

Cited By ~ 36

Author(s):

Fernando R. Fernandez ◽

W. Hamish Mehaffey ◽

Ray W. Turner

Keyword(s):

Pyramidal Cells ◽

Firing Frequency ◽

Weakly Electric Fish ◽

Dynamical Analysis ◽

Central Neurons ◽

Electrophysiological Recordings ◽

A Cell ◽

Dendritic Spike ◽

Weakly Electric ◽

The Relationship

Many central neurons support active dendritic spike backpropagation mediated by voltage-gated currents. Active spikes in dendrites have been shown capable of providing feedback to the soma to influence somatic excitability and firing dynamics through a depolarizing afterpotential (DAP). In pyramidal cells of the electrosensory lobe of weakly electric fish, Na+ spikes in dendrites undergo a frequency-dependent broadening that enhances the DAP to increase somatic firing frequency. We use a combination of dynamical analysis and electrophysiological recordings to demonstrate that spike broadening in dendrites is primarily caused by a cumulative inactivation of dendritic Na+ current. We further show that a reduction in dendritic Na+ current increases excitability by decreasing the interspike interval and promoting burst firing. This process arises when inactivation of dendritic Na+ current shifts the latency of the dendritic spike to delay the arrival of the DAP sufficiently to increase its impact on somatic membrane potential despite a reduction in dendritic excitability. Furthermore, the relationship between dendritic Na+ current density and somatic excitability is nonmonotonic, as intermediate levels of dendritic Na+ current exert the greatest excitatory influence. These results reveal that temporal shifts in dendritic spike firing provide a novel means for backpropagating spikes to influence the final output of a cell.

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Conditional Spike Backpropagation Generates Burst Discharge in a Sensory Neuron

Journal of Neurophysiology ◽

10.1152/jn.2000.84.3.1519 ◽

2000 ◽

Vol 84 (3) ◽

pp. 1519-1530 ◽

Cited By ~ 64

Author(s):

N. Lemon ◽

R. W. Turner

Keyword(s):

Refractory Period ◽

Interspike Interval ◽

Pyramidal Cells ◽

Weakly Electric Fish ◽

Interspike Intervals ◽

Frequency Dependent ◽

Spike Discharge ◽

Burst Discharge ◽

Dendritic Spike

Backpropagating dendritic Na+spikes generate a depolarizing afterpotential (DAP) at the soma of pyramidal cells in the electrosensory lateral line lobe (ELL) of weakly electric fish. Repetitive spike discharge is associated with a progressive depolarizing shift in somatic spike afterpotentials that eventually triggers a high-frequency spike doublet and subsequent burst afterhyperpolarization (bAHP). The rhythmic generation of a spike doublet and bAHP groups spike discharge into an oscillatory burst pattern. This study examined the soma-dendritic mechanisms controlling the depolarizing shift in somatic spike afterpotentials, and the mechanism by which spike doublets terminate spike discharge. Intracellular recordings were obtained from ELL pyramidal somata and apical dendrites in an in vitro slice preparation. The pattern of spike discharge was equivalent in somatic and dendritic regions, reflecting the backpropagation of spikes from soma to dendrites. There was a clear frequency-dependent threshold in the transition from tonic to burst discharge, with bursts initiated when interspike intervals fell between ∼3–7 ms. Removal of all backpropagating spikes by dendritic TTX ejection revealed that the isolated somatic AHPs were entirely stable at the interspike intervals that generated burst discharge. As such, the depolarizing membrane potential shift during repetitive discharge could be attributed to a potentiation of DAP amplitude. Potentiation of the DAP was due to a frequency-dependent broadening and temporal summation of backpropagating dendritic Na+ spikes. Spike doublets were generated with an interspike interval close to, but not within, the somatic spike refractory period. In contrast, the interspike interval of spike doublets always fell within the longer dendritic refractory period, preventing backpropagation of the second spike of the doublet. The dendritic depolarization was thus abruptly removed from one spike to the next, allowing the burst to terminate when the bAHP hyperpolarized the membrane. The transition from tonic to burst discharge was dependent on the number and frequency of spikes invoking dendritic spike summation, indicating that burst threshold depends on the immediate history of cell discharge. Spike frequency thus represents an important condition that determines the success of dendritic spike invasion, establishing an intrinsic mechanism by which backpropagating spikes can be used to generate a rhythmic burst output.

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Oscillatory and burst discharge in the apteronotid electrosensory lateral line lobe

Journal of Experimental Biology ◽

10.1242/jeb.202.10.1255 ◽

1999 ◽

Vol 202 (10) ◽

pp. 1255-1265 ◽

Cited By ~ 1

Author(s):

R.W. Turner ◽

L. Maler

Keyword(s):

Feature Extraction ◽

Lateral Line ◽

Pyramidal Cell ◽

Frequency Tuning ◽

Pyramidal Cells ◽

Weakly Electric Fish ◽

Burst Discharge ◽

Sensory Maps

Oscillatory and burst discharge is recognized as a key element of signal processing from the level of receptor to cortical output cells in most sensory systems. The relevance of this activity for electrosensory processing has become increasingly apparent for cells in the electrosensory lateral line lobe (ELL) of gymnotiform weakly electric fish. Burst discharge by ELL pyramidal cells can be recorded in vivo and has been directly associated with feature extraction of electrosensory input. In vivo recordings have also shown that pyramidal cells are differentially tuned to the frequency of amplitude modulations across three ELL topographic maps of electroreceptor distribution. Pyramidal cell recordings in vitro reveal two forms of oscillatory discharge with properties consistent with pyramidal cell frequency tuning in vivo. One is a slow oscillation of spike discharge arising from local circuit interactions that exhibits marked changes in several properties across the sensory maps. The second is a fast, intrinsic form of burst discharge that incorporates a newly recognized interaction between somatic and dendritic membranes. These findings suggest that a differential regulation of oscillatory discharge properties across sensory maps may underlie frequency tuning in the ELL and influence feature extraction in vivo.

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Oscillatory and burst discharge across electrosensory topographic maps

Journal of Neurophysiology ◽

10.1152/jn.1996.76.4.2364 ◽

1996 ◽

Vol 76 (4) ◽

pp. 2364-2382 ◽

Cited By ~ 34

Author(s):

R. W. Turner ◽

J. R. Plant ◽

L. Maler

Keyword(s):

Electric Fields ◽

Pyramidal Cell ◽

Unit Activity ◽

Pyramidal Cells ◽

Average Frequency ◽

Afferent Input ◽

Weakly Electric Fish ◽

Burst Discharge

1. Three parallel maps of the distribution of tuberous electroreceptor inputs are found in the medullary electrosensory lateral line lobe (ELL) of weakly electric fish. Pyramidal cells in each map are known to respond differentially to the frequency of amplitude modulations (AMs) of external electric fields in vivo. We used an in vitro ELL slice preparation of Apteronotus leptorhynchus to compare the characteristics of spontaneously active single units across the three tuberous maps. It was our objective to determine whether spontaneous bursting activity of pyramidal cells in each map correlates with the known AM frequency selectivities of pyramidal cells in vivo. 2. Single-unit discharges were recorded from the pyramidal cell layer of the centromedial segment (CMS), centrolateral segment (CLS), and lateral segment (LS) of the ELL. Stochastic analysis of interspike intervals (ISIs) was used to identify bursting and nonbursting unit activity, and to separately analyze intra- and interburst ISIs. Four ISI patterns were identified as 1) bursting, 2) regular spiking, 3) irregular spiking, and 4) highly irregular spiking. This work focuses primarily on the characteristics of bursting units across the ELL segments. 3. Spontaneous bursting discharge was identified in all three maps (68 of 97 units), with several characteristics changing in a gradual manner across the maps. The coefficient of variation (CV) of ISIs and intraburst ISIs decreased significantly from the CMS to the LS, whereas the CV of burst periods increased significantly from the CMS to the LS. Autocorrelations and power spectral density analysis identified units discharging in an oscillatory manner with the following ratio: CMS, 75%; CLS, 4%; LS, 8%. 4. The mean period of spike bursts decreased significantly across the segments (CMS, 2.7 s; CLS, 1.2 s; LS, 1.1 s) primarily because of a shortening of mean burst duration (CMS, 1.0 s; CLS, 0.1 s; LS, 0.05 s). The average number of spikes per burst decreased significantly across the maps (CMS, 61; CLS, 8; LS, 8), whereas the average frequency of spikes per burst increased (CMS, 90 Hz; CLS, 130 Hz; LS, 178 Hz), mainly through an increase in the maximal frequencies attained by units within each map. 5. Bursts in the CMS were unstructured in that the intraburst ISIs were serially independent, whereas for many units in the CLS and especially the LS there were serial dependencies of successive spikes, with alternating short and long ISIs during the burst. 6. These data reveal that the characteristics of bursting unit activity differ between the CMS, CLS, and LS maps in vitro, implying a modulation of the factors underlying burst discharge across multiple sensory maps. Because the pattern of change in burst activity between these maps parallels that of pyramidal cell AM frequency selectivity in vivo, oscillatory and burst discharge may represent the cellular mechanism used to tune these cells to specific frequencies of afferent input during electrolocation and electrocommunication.

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Interval Coding. I. Burst Interspike Intervals as Indicators of Stimulus Intensity

Journal of Neurophysiology ◽

10.1152/jn.00987.2006 ◽

2007 ◽

Vol 97 (4) ◽

pp. 2731-2743 ◽

Cited By ~ 62

Author(s):

Anne-Marie M. Oswald ◽

Brent Doiron ◽

Leonard Maler

Keyword(s):

Stimulus Intensity ◽

Information Transfer ◽

Pyramidal Cells ◽

Sensory Stimulation ◽

Weakly Electric Fish ◽

Interspike Intervals ◽

Direct Stimulation ◽

Distinct Features ◽

Weakly Electric

Short interspike intervals such as those that occur during burst firing are hypothesized to be distinct features of the neural code. Although a number of correlations between the occurrence of burst events and aspects of the stimulus have been identified, the relationship between burst characteristics and information transfer is uncertain. Pyramidal cells in the electrosensory lobe of the weakly electric fish, Apteronotus leptorhynchus, respond to dynamic broadband electrosensory stimuli with bursts and isolated spikes. In the present study, we mimic synaptic input during sensory stimulation by direct stimulation of electrosensory pyramidal cells with broadband current in vitro. The pyramidal cells respond to this stimulus with burst interspike intervals (ISIs) that are reliably and precisely correlated with the intensity of stimulus upstrokes. We found burst ISIs must differ by a minimum of 2 ms to discriminate, with low error, differences in stimulus intensity. Based on these results, we define and quantify a candidate interval code for the processing of sensory input. Finally, we demonstrate that interval coding is restricted to short ISIs such as those generated in burst events and that the proposed interval code is distinct from rate and timing codes.

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Nonlinear Information Processing in a Model Sensory System

Journal of Neurophysiology ◽

10.1152/jn.01296.2005 ◽

2006 ◽

Vol 95 (5) ◽

pp. 2933-2946 ◽

Cited By ~ 62

Author(s):

Maurice J. Chacron

Keyword(s):

Pyramidal Cell ◽

Sensory System ◽

Sensory Information ◽

Pyramidal Cells ◽

Spike Trains ◽

Weakly Electric Fish ◽

Synaptic Noise ◽

Optimal Linear ◽

Pharmacological Blockade ◽

Weakly Electric

Understanding the mechanisms by which sensory neurons encode and decode information remains an important goal in neuroscience. We quantified the performance of optimal linear and nonlinear encoding models in a well-characterized sensory system: the electric sense of weakly electric fish. We show that linear encoding models generally perform better under spatially localized stimulation than under spatially diffuse stimulation. Through pharmacological blockade of feedback input and spatial saturation of the receptive field center, we show that there is significantly less synaptic noise under spatially diffuse stimuli as compared with spatially localized stimuli. Modeling results suggest that pyramidal cells nonlinearly encode sensory information through shunting in their dendrites and clarify the influence of synaptic noise on the performance of linear encoding models. Finally, we used information theory to quantify the performance of linear decoders. While the optimal linear decoder for spatially localized stimuli could capture 60% of the information in pyramidal cell spike trains, the optimal linear decoder for spatially diffuse stimuli could only capture 40% of the information. These results show that nonlinear decoders are necessary to fully access information in pyramidal cell spike trains, and we discuss potential mechanisms by which higher-order neurons could decode this information.

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