scholarly journals Location and Plasticity of the Sodium Spike Initiation Zone in Nociceptive Terminals In Vivo

Neuron ◽  
2019 ◽  
Vol 102 (4) ◽  
pp. 801-812.e5 ◽  
Author(s):  
Robert H. Goldstein ◽  
Omer Barkai ◽  
Almudena Íñigo-Portugués ◽  
Ben Katz ◽  
Shaya Lev ◽  
...  
Keyword(s):  
Initiation Zone ◽  
Spike Initiation

Action Potential Initiation and Propagation in CA3 Pyramidal Axons

2007 ◽  
Vol 97 (5) ◽  
pp. 3460-3472 ◽  
Author(s):  
Julian P. Meeks ◽  
Steven Mennerick
Keyword(s):  
Sodium Channel ◽  
Conduction Velocity ◽  
Initiation Site ◽  
Initiation Zone ◽  
Initiation And Propagation ◽  
Threshold Crossing ◽  
Action Potential Initiation ◽  
Ca3 Neurons ◽  
Zone Characteristic ◽  
Spike Initiation

Thin, unmyelinated axons densely populate the mammalian hippocampus and cortex. However, the location and dynamics of spike initiation in thin axons remain unclear. We investigated basic properties of spike initiation and propagation in CA3 neurons of juvenile rat hippocampus. Sodium channel alpha subunit distribution and local applications of tetrodotoxin demonstrate that the site of first threshold crossing in CA3 neurons is ∼35 μm distal to the soma, somewhat more proximal than our previous estimates. This discrepancy can be explained by the finding, obtained with simultaneous whole cell somatic and extracellular axonal recordings, that a zone of axon stretching to ∼100 μm distal to the soma reaches a maximum rate of depolarization nearly synchronously by the influx of sodium from the high-density channels. Models of the proximal axon incorporating observed distributions of sodium channel staining recapitulated salient features of somatic and axonal spike waveforms, including the predicted initiation zone, characteristic spike latencies, and conduction velocity. The preferred initiation zone was unaltered by stimulus strength or repetitive spiking, but repetitive spiking increased threshold and significantly slowed initial segment recruitment time and conduction velocity. Our work defines the dynamics of initiation and propagation in hippocampal principal cell axons and may help reconcile recent controversies over initiation site in other axons.

scholarly journals Distal Spike Initiation Zone Location Estimation by Morphological Simulation of Ionic Current Filtering Demonstrated in a Novel Model of an Identified Drosophila Motoneuron

2015 ◽  
Vol 11 (5) ◽  
pp. e1004189 ◽  
Author(s):  
Cengiz Günay ◽  
Fred H. Sieling ◽  
Logesh Dharmar ◽  
Wei-Hsiang Lin ◽  
Verena Wolfram ◽  
...  
Keyword(s):  
Ionic Current ◽  
Location Estimation ◽  
Initiation Zone ◽  
Spike Initiation ◽  
Novel Model

scholarly journals Identification of Primary Initiation Sites for DNA Replication in the Hamster Dihydrofolate Reductase Gene Initiation Zone

1998 ◽  
Vol 18 (6) ◽  
pp. 3266-3277 ◽  
Author(s):  
Takehiko Kobayashi ◽  
Theo Rein ◽  
Melvin L. DePamphilis
Keyword(s):  
Dihydrofolate Reductase ◽  
Relative Number ◽  
Replication Origins ◽  
Two Dimensional Gel Electrophoresis ◽  
Initiation Zone ◽  
Reductase Gene ◽  
Dna Strands ◽  
Early Replication ◽  
Multiple Replication

ABSTRACT Mammalian replication origins appear paradoxical. While some studies conclude that initiation occurs bidirectionally from specific loci, others conclude that initiation occurs at many sites distributed throughout large DNA regions. To clarify this issue, the relative number of early replication bubbles was determined at 26 sites in a 110-kb locus containing the dihydrofolate reductase (DHFR)-encoding gene in CHO cells; 19 sites were located within an 11-kb sequence containing ori-β. The ratio of ∼0.8-kb nascent DNA strands to nonreplicated DNA at each site was quantified by competitive PCR. Nascent DNA was defined either as DNA that was labeled by incorporation of bromodeoxyuridine in vivo or as RNA-primed DNA that was resistant to λ-exonuclease. Two primary initiation sites were identified within the 12-kb region, where two-dimensional gel electrophoresis previously detected a high frequency of replication bubbles. A sharp peak of nascent DNA occurred at the ori-β origin of bidirectional replication where initiation events were 12 times more frequent than at distal sequences. A second peak occurred 5 kb downstream at a previously unrecognized origin (ori-β′). Thus, the DHFR gene initiation zone contains at least three primary initiation sites (ori-β, ori-β′, and ori-γ), suggesting that initiation zones in mammals, like those in fission yeast, consist of multiple replication origins.

scholarly journals G Clustering Is Important for the Initiation of Transcription-Induced R-Loops In Vitro, whereas High G Density without Clustering Is Sufficient Thereafter

2009 ◽  
Vol 29 (11) ◽  
pp. 3124-3133 ◽  
Author(s):  
Deepankar Roy ◽  
Michael R. Lieber
Keyword(s):  
Rna Polymerase ◽  
Cytidine Deaminase ◽  
Loop Formation ◽  
Initiation Phase ◽  
Initiation Zone ◽  
Loop Region ◽  
Switch Regions ◽  
Dna Strand

ABSTRACT R-loops form cotranscriptionally in vitro and in vivo at transcribed duplex DNA regions when the nascent RNA is G-rich, particularly with G clusters. This is the case for phage polymerases, as used here (T7 RNA polymerase), as well as RNA polymerases in bacteria, Saccharomyces cerevisiae, avians, mice, and humans. The nontemplate strand is left in a single-stranded configuration within the R-loop region. These structures are known to form at mammalian immunoglobulin class switch regions, thus exposing regions of single-stranded DNA for the action of AID, a single-strand-specific cytidine deaminase. R-loops form by thread-back of the RNA onto the template DNA strand, and here we report that G clusters are extremely important for the initiation phase of R-loop formation. Even very short regions with one GGGG sequence can initiate R-loops much more efficiently than random sequences. The high efficiencies observed with G clusters cannot be achieved by having a very high G density alone. Annealing of the transcript, which is otherwise disadvantaged relative to the nontemplate DNA strand because of unfavorable proximity while exiting the RNA polymerase, can offer greater stability if it occurs at the G clusters, thereby initiating an R-loop. R-loop elongation beyond the initiation zone occurs in a manner that is not as reliant on G clusters as it is on a high G density. These results lead to a model in which G clusters are important to nucleate the thread-back of RNA for R-loop initiation and, once initiated, the elongation of R-loops is primarily determined by the density of G on the nontemplate DNA strand. Without both a favorable R-loop initiation zone and elongation zone, R-loop formation is inefficient.

scholarly journals Crustacean cardiac ganglion model reveals constraints on morphology and conductances

2021 ◽  
Author(s):  
Daniel S Dopp ◽  
Pranit S Samarth ◽  
Jing S Wang ◽  
Daniel R Kick ◽  
David J Schulz ◽  
...  
Keyword(s):  
Single Cell ◽  
Large Cell ◽  
Biophysical Model ◽  
Cardiac Ganglion ◽  
Initiation Zone ◽  
Unknown Structure ◽  
Network Coordinates ◽  
Large Motor ◽  
Motor Cells ◽  
Spike Initiation

The crustacean cardiac ganglion (CG) network coordinates the rhythmic contractions of the heart muscle to control the circulation of blood. The network consists of 9 cells, 5 large motor cells (LC1-5) and 4 small endogenous pacemaker cells (SCs). We report a new three-compartmental biophysical model of an LC that is morphologically realistic and includes provision for inputs from the SCs via a gap-junction coupled spike-initiation-zone (SIZ) compartments. To determine physiologically viable LC models in this realistic configuration, maximal conductances in three compartments of an LC are determined by random sampling from a biologically-characterized 9D-parameter space, followed by a three stage rejection protocol that checks for conformity with electrophysiological features from single cell traces. LC models that pass the single cell rejection protocol are then incorporated into a network model which is then used in a final rejection protocol stage. Using disparate experimental data, the study provides hitherto unknown structure-function insights related to the crustacean cardiac ganglion large cell, including predictions about morphology including the role of its SIZ, and the differential roles of active conductances in the three compartments. Further, we extend analyses of emergent conductance relationships and correlations in model neurons relative to their biological counterparts, allowing us to make inferences both with respect to the biological system as well as the implications of the ability to detect such relationships in populations of model neurons going forward.

Synaptic integration in excitatory and inhibitory crayfish motoneurons

1987 ◽  
Vol 57 (5) ◽  
pp. 1425-1445 ◽  
Author(s):  
D. H. Edwards ◽  
B. Mulloney
Keyword(s):  
Action Potential ◽  
Time Course ◽  
Input Resistance ◽  
Excitatory Postsynaptic Potential ◽  
Fe Model ◽  
Common Input ◽  
Giant Neuron ◽  
Initiation Zone ◽  
Contraction And Relaxation ◽  
Spike Initiation

The passive integrative properties of two crayfish abdominal motoneurons, the fast flexor inhibitor (FI) and a posterior, ipsilateral fast flexor excitor (FE), were studied electrophysiologically and through simulations with multicompartment models of their electrotonic structures. Responses of the models to simulated giant neuron input were quite similar to the motoneurons' responses to giant neuron stimulation, which suggests that differences in the electrotonic structures and the sites of synaptic input to the two cells can account in large part for differences in their responses to a common input. A full action potential created in the initial axon compartment of the FI model produced attenuated potentials in the adjacent integrating segment compartment and contralateral soma compartment. These potentials are similar in amplitude and time course to attenuated antidromic action potentials recorded in the corresponding regions of the FI neuron. A location of the spike initiation zone of the FI at the initial axon segment is consistent with this result. The responses of FI to ipsi- and contralateral inputs are different. Shock of a single abdominal second root produced a larger, faster rising excitatory postsynaptic potential in the ipsilateral FI soma than in the contralateral soma. Second root shock also caused the contralateral FI to produce an action potential either alone or before the ipsilateral FI neuron. Responses of the FI model to ipsilateral and contralateral inputs differ in the same way as the cell's responses. Inputs to the FI model that are ipsilateral to the soma compartment produce larger responses there than do contralateral inputs. Conversely, those contralateral inputs produce larger responses in the initial axon compartment than do ipsilateral inputs. This difference results from the long integrating segment that connects the soma compartment to the initial axon compartment. These results can account for the FI responses to lateralized inputs. Unlike the responses of FIs, the soma responses of contralaterally homologous FEs to ipsilateral and contralateral second root shocks were similar in waveform and amplitude, with the ipsilateral root producing the larger response. This result is consistent with theoretical results from the FE model simulations. We conclude that a smaller size, larger input resistance and shorter membrane time constant allow the FE to respond to giant neuron input before the FI, and so help to achieve the proper timing of flexor contraction and relaxation during a tailflip.(ABSTRACT TRUNCATED AT 400 WORDS)

Voltage-Dependent Events in the Dendritic Tree

1998 ◽  
Author(s):  
Christof Koch
Keyword(s):  
Dendritic Tree ◽  
Biophysical Modeling ◽  
Functional Roles ◽  
Initiation Zone ◽  
Cable Theory ◽  
Membrane Conductances ◽  
Cable Properties ◽  
Voltage Dependent ◽  
The Face ◽  
Spike Initiation

So far, we worked under the convenient fiction that active, voltage-dependent membrane conductances are confined to the spike initiation zone at or close to the cell body and that the dendritic tree is essentially passive. Under the influence of one-dimensional passive cable theory, as refined by Rail and his school (Chaps. 2 and 3), the passive model of dendritic integration of synaptic inputs has become dominant and is taught in all the textbooks. Paradoxically, from the earliest days of intracellular recordings from the fat dendrites of spinal cord motoneurons with the aid of glass microelectrodes, active dendritic responses had been witnessed (Brock, Coombs, and Eccles, 1952; Eccles, Libet, and Young, 1958). Today, there exists overwhelming evidence for a host of voltage-dependent sodium and calcium-conductances in the dendritic tree. In the following section we summarize the experimental evidence and discuss current biophysical modeling efforts focusing on the question of the existence and genesis of fast all-or-none electrical events in the dendrites. We then turn toward possible functional roles of active dendritic processing. One word of advice. It has been argued that linear cable theory as applied to dendrites and taught in the first chapters of this book is irrelevant in the face of all this evidence for active processing and can be relegated to the dustbin. However, this would be a mistake. Under many physiological conditions these nonlinearities will not be relevant. Even if they are, the resistive and capacitive cable properties of the dendrites profoundly influence the initiation and propagation of dendritic action potentials and other active phenomena. Thus, for a complete understanding of the events in active dendritic trees we need to be thoroughly versed in cable theory. The issue of dendritic all-or-none electrical events must be seen as separate from the broader question of the existence and nature of active, that is, voltage-dependent, membrane conductances in the dendritic tree.

Biophysical studies of mechanoreceptors

1986 ◽  
Vol 60 (4) ◽  
pp. 1107-1115 ◽  
Author(s):  
P. Grigg
Keyword(s):  
Action Potentials ◽  
Dynamic Responses ◽  
Initiation Zone ◽  
Biophysical Studies ◽  
Electrogenic Na Pump ◽  
Action Potential Initiation ◽  
Branching Point ◽  
The Many ◽  
Spike Initiation ◽  
Potential Initiation

Mechanoreception can be viewed as a series of sequential mechanical and ionic processes that take place in mechanosensitive end organs and in the terminals of the nerves that innervate them. Stimuli act on a transducer after being transmitted through some material having a combination of elastic and viscoelastic properties. Channels that open under membrane loading have recently been described in muscle cells and are presented as a model for transduction. When open these channels are cation specific. Ions passing through transducer channels depolarize a spike-initiating zone on the cell. These currents may also activate other conductances in the cell, so that the total generator current may have many components. In many mechanoreceptors, action potential initiation results in activation of an electrogenic Na+ pump at the spike-initiation zone, which modifies the threshold for subsequent action potentials. Action potentials initiated in the many branches of a single sensory axon interact at the branching point of the axon. The rules governing this interaction are complex. The above factors, together or separately, are responsible for the dynamic responses and adaptation observed in mechanoreceptors.

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