scholarly journals SK Channels Gate Information Processing In Vivo by Regulating an Intrinsic Bursting Mechanism Seen In Vitro

2009 ◽  
Vol 102 (4) ◽  
pp. 2273-2287 ◽  
Author(s):  
Natalia Toporikova ◽  
Maurice J. Chacron
Keyword(s):  
Action Potentials ◽  
Time Course ◽  
Sensory Input ◽  
Calcium Influx ◽  
Fundamental Problem ◽  
Pyramidal Cells ◽  
Dendritic Morphology ◽  
Weakly Electric Fish

Understanding the mechanistic substrates of neural computations that lead to behavior remains a fundamental problem in neuroscience. In particular, the contributions of intrinsic neural properties such as burst firing and dendritic morphology to the processing of behaviorally relevant sensory input have received much interest recently. Pyramidal cells within the electrosensory lateral line lobe of weakly electric fish display an intrinsic bursting mechanism that relies on somato-dendritic interactions when recorded in vitro: backpropagating somatic action potentials trigger dendritic action potentials that lead to a depolarizing afterpotential (DAP) at the soma. We recorded intracellularly from these neurons in vivo and found firing patterns that were quite different from those seen in vitro: we found no evidence for DAPs as each somatic action potential was followed by a pronounced afterhyperpolarization (AHP). Calcium chelators injected in vivo reduced the AHP, thereby unmasking the DAP and inducing in vitro-like bursting in pyramidal cells. These bursting dynamics significantly reduced the cell's ability to encode the detailed time course of sensory input. We performed additional in vivo pharmacological manipulations and mathematical modeling to show that calcium influx through N-methyl-d-aspartate (NMDA) receptors activate dendritic small conductance (SK) calcium-activated potassium channels, which causes an AHP that counteracts the DAP and leads to early termination of the burst. Our results show that ion channels located in dendrites can have a profound influence on the processing of sensory input by neurons in vivo through the modulation of an intrinsic bursting mechanism.

Properties of Action-Potential Initiation in Neocortical Pyramidal Cells: Evidence From Whole Cell Axon Recordings

2007 ◽  
Vol 97 (1) ◽  
pp. 746-760 ◽  
Author(s):  
Yousheng Shu ◽  
Alvaro Duque ◽  
Yuguo Yu ◽  
Bilal Haider ◽  
David A. McCormick
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Initial Segment ◽  
Pyramidal Cells ◽  
Synaptic Activity ◽  
Up States ◽  
Action Potential Initiation ◽  
Potential Initiation

Cortical pyramidal cells are constantly bombarded by synaptic activity, much of which arises from other cortical neurons, both in normal conditions and during epileptic seizures. The action potentials generated by barrages of synaptic activity may exhibit a variable site of origin. Here we performed simultaneous whole cell recordings from the soma and axon or soma and apical dendrite of layer 5 pyramidal neurons during normal recurrent network activity (up states), the intrasomatic or intradendritic injection of artificial synaptic barrages, and during epileptiform discharges in vitro. We demonstrate that under all of these conditions, the real or artificial synaptic bombardments propagate through the dendrosomatic-axonal arbor and consistently initiate action potentials in the axon initial segment that then propagate to other parts of the cell. Action potentials recorded intracellularly in vivo during up states and in response to visual stimulation exhibit properties indicating that they are typically initiated in the axon. Intracortical axons were particularly well suited to faithfully follow the generation of action potentials by the axon initial segment. Action-potential generation was more reliable in the distal axon than at the soma during epileptiform activity. These results indicate that the axon is the preferred site of action-potential initiation in cortical pyramidal cells, both in vivo and in vitro, with state-dependent back propagation through the somatic and dendritic compartments.

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.

Oscillatory and burst discharge in the apteronotid electrosensory lateral line lobe

1999 ◽  
Vol 202 (10) ◽  
pp. 1255-1265 ◽  
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.

Neural architecture of the electrosensory lateral line lobe: adaptations for coincidence detection, a sensory searchlight and frequency-dependent adaptive filtering

1999 ◽  
Vol 202 (10) ◽  
pp. 1243-1253 ◽  
Author(s):  
N.J. Berman ◽  
L. Maler
Keyword(s):  
Lateral Line ◽  
Activity Patterns ◽  
Pyramidal Cells ◽  
Coincidence Detection ◽  
Weakly Electric Fish ◽  
In Vivo Studies ◽  
Frequency Dependent ◽  
Postsynaptic Potentials

The electrosensory lateral line lobe (ELL) of weakly electric fish is the only nucleus that receives direct input from peripheral electroreceptor afferents. This review summarises the neurotransmitters, receptors and second messengers identified in the intrinsic circuitry of the ELL and the extrinsic descending direct and indirect feedback pathways, as revealed by recent in vitro and in vivo studies. Several hypotheses of circuitry function are examined on this basis and on the basis of recent functional evidence: (1) fast primary afferent excitatory postsynaptic potentials (EPSPs) and fast granule cell 2 GABAA inhibitory postsynaptic potentials (IPSPs) suggest the involvement of basilar pyramidal cells in coincidence detection; (2) voltage-dependent EPSPs and IPSPs, dendritic spike bursts and frequency-dependent synaptic facilitation support a sensory searchlight role for the direct feedback pathway; and (3) the contributions of distal and proximal inhibition, anti-Hebbian plasticity and beam versus isolated fiber activity patterns are discussed with reference to an adaptive spatio-temporal filtering role for the indirect descending pathway.

scholarly journals Cellular mechanisms for response heterogeneity among L2/3 pyramidal cells in whisker somatosensory cortex

2014 ◽  
Vol 112 (2) ◽  
pp. 233-248 ◽  
Author(s):  
Justin Elstrott ◽  
Kelly B. Clancy ◽  
Haani Jafri ◽  
Igor Akimenko ◽  
Daniel E. Feldman
Keyword(s):  
Somatosensory Cortex ◽  
Pyramidal Cells ◽  
Dendritic Morphology ◽  
Membrane Properties ◽  
Intrinsic Excitability ◽  
High Threshold ◽  
Cellular Mechanisms ◽  
Inhibitory Conductance

Whisker deflection evokes sparse, low-probability spiking among L2/3 pyramidal cells in rodent somatosensory cortex (S1), with spiking distributed nonuniformly between more and less responsive cells. The cellular and local circuit factors that determine whisker responsiveness across neurons are unclear. To identify these factors, we used two-photon calcium imaging and loose-seal recording to identify more and less responsive L2/3 neurons in S1 slices in vitro, during feedforward recruitment of the L2/3 network by L4 stimulation. We observed a broad gradient of spike recruitment thresholds within local L2/3 populations, with low- and high-threshold cells intermixed. This recruitment gradient was significantly correlated across different L4 stimulation sites, and between L4-evoked and whisker-evoked responses in vivo, indicating that a substantial component of responsiveness is independent of tuning to specific feedforward inputs. Low- and high-threshold L2/3 pyramidal cells differed in L4-evoked excitatory synaptic conductance and intrinsic excitability, including spike threshold and the likelihood of doublet spike bursts. A gradient of intrinsic excitability was observed across neurons. Cells that spiked most readily to L4 stimulation received the most synaptic excitation but had the lowest intrinsic excitability. Low- and high-threshold cells did not differ in dendritic morphology, passive membrane properties, or L4-evoked inhibitory conductance. Thus multiple gradients of physiological properties exist across L2/3 pyramidal cells, with excitatory synaptic input strength best predicting overall spiking responsiveness during network recruitment.

Transient Signals Trigger Synchronous Bursts in an Identified Population of Neurons

2009 ◽  
Vol 102 (2) ◽  
pp. 714-723 ◽  
Author(s):  
Gary Marsat ◽  
Rémi D. Proville ◽  
Leonard Maler
Keyword(s):  
Low Frequency ◽  
Pyramidal Cells ◽  
Weakly Electric Fish ◽  
Transient Signal ◽  
Transient Signals ◽  
Communication Signals ◽  
Continuous Signal ◽  
Number Of Cells

It is an important task in neuroscience to find general principles that relate neural codes to the structure of the signals they encode. The structure of sensory signals can be described in many ways, but one important categorization distinguishes continuous from transient signals. We used the communication signals of the weakly electric fish to reveal how transient signals (chirps) can be easily distinguished from the continuous signal they disrupt. These communication signals—low-frequency sinusoids interrupted by high-frequency transients—were presented to pyramidal cells of the electrosensory lateral line lobe (ELL) during in vivo recordings. We show that a specific population of electrosensory neurons encodes the occurrence of the transient signal by synchronously producing a burst of spikes, whereas bursting was neither common nor synchronous in response to the continuous signal. We also confirmed that burst can be triggered by low-frequency modulations typical of prey signals. However, these bursts are more common in a different segment of the ELL and during spatially localized stimulation. These localized stimuli will elicit synchronized bursting only in a restricted number of cells the receptive fields of which overlap the spatial extent of the stimulus. Therefore the number of cells simultaneously producing a burst and the ELL segment responding most strongly may carry the information required to disambiguate chirps from prey signals. Finally we show that the burst response to chirps is due to a biophysical mechanism previously characterized by in vitro studies of electrosensory neurons. We conclude that bursting and synchrony across cells are important mechanisms used by sensory neurons to carry the information about behaviorally relevant but transient signals.

Oscillatory and burst discharge across electrosensory topographic maps

1996 ◽  
Vol 76 (4) ◽  
pp. 2364-2382 ◽  
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.

scholarly journals Synaptically Recruited Apical Currents Are Required to Initiate Axonal and Apical Spikes in Hippocampal Pyramidal Cells: Modulation by Inhibition

2005 ◽  
Vol 93 (2) ◽  
pp. 909-918 ◽  
Author(s):  
S. Canals ◽  
L. López-Aguado ◽  
O. Herreras
Keyword(s):  
Action Potentials ◽  
Pyramidal Cells ◽  
Excitatory Input ◽  
Synaptic Potentials ◽  
Local Inhibition ◽  
Voltage Dependent ◽  
Cell Firing

Dendritic voltage-dependent currents and inhibition modulate the information flow between synaptic and decision areas. Subthreshold and spike currents are sequentially recruited by synaptic potentials in the apical shaft of pyramidal cells, which may also decide cell output. We studied the global role of proximal apical recruited currents on cell output in vitro and in the anesthetized rat after local blockade of Na+ currents in the axon initial segment (AIS) or the proximal apical shaft and their modulation by inhibition. Microejection of TTX, field potentials, and intrasomatic and intradendritic recordings were employed. Dendritic population spikes (PSs) were much smaller in vitro, but the gross relations between synaptic and active currents are similar to in vivo. Activation of Schaffer collaterals triggered PSs and action potentials (APs) in the apical shaft that fully propagated to the axon. However, the specific blockade of proximal Na+ currents avoided cell firing, although antidromic PSs and APs readily invaded somata. The somatic depolarization of subthreshold excitatory postsynaptic potentials (EPSPs) also decreased to about 50%. These results were not due to decreased excitatory input by TTX. However, when GABAA inhibition was locally removed, Schaffer synaptic currents skipped the proximal dendrite and fired somatic PSs, although initiated at the AIS. It is concluded that apical currents recruited en passant by Schaffer synaptic potentials in the apical shaft constitute a necessary amplifier for this input to cause output decision. Local inhibition decides when and where an AP will initiate, constituting an efficient mechanism to discriminate and weight different inputs.

scholarly journals Background Synaptic Conductance and Precision of EPSP-Spike Coupling at Pyramidal Cells

2005 ◽  
Vol 93 (6) ◽  
pp. 3248-3256 ◽  
Author(s):  
Veronika Zsiros ◽  
Shaul Hestrin
Keyword(s):  
Time Course ◽  
Pyramidal Cells ◽  
Spike Timing ◽  
Synaptic Activity ◽  
Synaptic Conductance ◽  
Temporal Precision ◽  
Voltage Dependent ◽  
Cortical Slices

The temporal precision of converting excitatory postsynaptic potentials (EPSPs) into spikes at pyramidal cells is critical for the coding of information in the cortex. Several in vitro studies have shown that voltage-dependent conductances in pyramidal cells can prolong the EPSP time course resulting in an imprecise EPSP-spike coupling. We have used dynamic-clamp techniques to mimic the in vivo background synaptic conductance in cortical slices and investigated how the ongoing synaptic activity may affect the EPSP time course near threshold and the EPSP spike coupling. We report here that background synaptic conductance dramatically diminished the depolarization related prolongation of the EPSPs in pyramidal cells and improved the precision of spike timing. Furthermore, we found that background synaptic conductance can affect the interaction among action potentials in a spike train. Thus the level of ongoing synaptic activity in the cortex may regulate the capacity of pyramidal cells to process temporal information.

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

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