Faculty Opinions recommendation of Silent synapses generate sparse and orthogonal action potential firing in adult-born hippocampal granule cells.

In adult neurogenesis young neurons connect to the existing network via formation of thousands of new synapses. At early developmental stages, glutamatergic synapses are sparse, immature and functionally 'silent', expressing mainly NMDA receptors. Here we show in 2- to 3-week-old young neurons of adult mice, that brief-burst activity in glutamatergic fibers is sufficient to induce postsynaptic AP firing in the absence of AMPA receptors. The enhanced excitability of the young neurons lead to efficient temporal summation of small NMDA currents, dynamic unblocking of silent synapses and NMDA-receptor-dependent AP firing. Therefore, early synaptic inputs are powerfully converted into reliable spiking output. Furthermore, due to high synaptic gain, small dendritic trees and sparse connectivity, neighboring young neurons are activated by different distinct subsets of afferent fibers with minimal overlap. Taken together, synaptic recruitment of young neurons generates sparse and orthogonal AP firing, which may support sparse coding during hippocampal information processing.

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Synaptic integration in a model of cerebellar granule cells

Journal of Neurophysiology ◽

10.1152/jn.1994.72.2.999 ◽

1994 ◽

Vol 72 (2) ◽

pp. 999-1009 ◽

Cited By ~ 149

Author(s):

F. Gabbiani ◽

J. Midtgaard ◽

T. Knopfel

Keyword(s):

Action Potential ◽

Granule Cell ◽

Granule Cells ◽

Mossy Fiber ◽

Potassium Conductance ◽

Time Interval ◽

Synaptic Current ◽

Action Potential Firing ◽

Potential Firing ◽

Kinetics Of

1. We have developed a compartmental model of a turtle cerebellar granule cell consisting of 13 compartmentds that represent the soma and 4 dendrites. We used this model to investigate the synaptic integration of mossy fiber inputs in granule cells. 2. The somatic compartment contained six active ionic conductances: a sodium conductance with fast activation and inactivation kinetics, gNa; a high-voltage-activated calcium conductance, gCa(HVA); a delayed potassium conductance, gK(DR); a transient potassium conductance, gK(A); a slowly relaxing mixed Na+/K+ conductance activating at hyperpolarized membrane potentials, gH, and a calcium- and voltage-dependent potassium conductance, gK(Ca). The kinetics of these conductances was derived from electrophysiological studies in a variety of preparations, including turtle and rat granule cells. 3. In the soma, dynamics of intracellular free Ca2+ was modeled by incorporation of a Na+/Ca2+ exchanger, radial diffusion, and binding sites for Ca2+. 4. The model of the turtle granule cell exhibited depolarization-induced action potential firing with properties closely resembling those seen with intracellular recordings in turtle granule cells in vitro. 5. In the most distal compartments of the dendrites, mossy fiber activity induced synaptic currents mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartate (NMDA)-type of glutamate receptors. The strength of synaptic inputs chosen was such that the synaptic potential induced by synchronous activation of two mossy fiber synapses reached threshold for induction of a single action potential. 6. The slow time course of the NMDA synaptic current together with the slow relaxation kinetics of gH significantly affected the temporal summation of excitatory synaptic potentials. A priming action potential evoked by mossy fiber stimulation increased the maximal time interval between two synaptic potentials capable to reach again threshold for a subsequent action potential. This time interval then decreased in parallel with the decay of the NMDA synaptic current, reached a minimum after 200 ms, and slowly recovered with reactivation of gH. 7. Repetitive, steady activation of synaptic conductances by a single mossy fiber at different frequencies induced action potential firing with a sharp threshold at 12 Hz. Activity of a single or of several mossy fibers induced firing of the granule cell at a frequency close to that induced when the average synaptic current was directly injected into the cell. The mossy fiber activity-granule cell firing frequency curve was close to linear with a slope of about one-half for input frequencies < or = 400 Hz.(ABSTRACT TRUNCATED AT 400 WORDS)

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Bidirectional GABAergic control of action potential firing in newborn hippocampal granule cells

Nature Neuroscience ◽

10.1038/nn.4218 ◽

2016 ◽

Vol 19 (2) ◽

pp. 263-270 ◽

Cited By ~ 34

Author(s):

Stefanie Heigele ◽

Sébastien Sultan ◽

Nicolas Toni ◽

Josef Bischofberger

Keyword(s):

Action Potential ◽

Granule Cells ◽

Action Potential Firing ◽

Potential Firing

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Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons

Journal of Neurophysiology ◽

10.1152/jn.00500.2007 ◽

2007 ◽

Vol 98 (6) ◽

pp. 3666-3676 ◽

Cited By ~ 8

Author(s):

Hai Xia Zhang ◽

Liu Lin Thio

Keyword(s):

Action Potential ◽

Action Potentials ◽

Hippocampal Neurons ◽

Neuronal Excitability ◽

Hippocampal Slices ◽

Glycine Receptors ◽

Inhibitory Effects ◽

Action Potential Firing ◽

Embryonic Mouse ◽

Potential Firing

Although extracellular Zn2+ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn2+ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn2+ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 μM Zn2+, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 μM glycine (EC25) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 μM Zn2+. At least part of this effect resulted from Zn2+ enhancing the GlyR-induced decrease in input resistance. Sustained 20 μM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg2+. However, sustained 20 μM glycine applications depressed neuronal bursting in 1 μM Zn2+. Zn2+ did not enhance the inhibitory effects of sustained 60 μM glycine (EC70) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn2+ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn2+ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.

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The thalamic low-threshold Ca 2+ potential: a key determinant of the local and global dynamics of the slow (<1 Hz) sleep oscillation in thalamocortical networks

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2011.0126 ◽

2011 ◽

Vol 369 (1952) ◽

pp. 3820-3839 ◽

Cited By ~ 14

Author(s):

Vincenzo Crunelli ◽

Adam C. Errington ◽

Stuart W. Hughes ◽

Tibor I. Tóth

Keyword(s):

Action Potential ◽

Slow Oscillation ◽

Global Dynamics ◽

Action Potential Firing ◽

Local And Global Dynamics ◽

Up States ◽

Potential Firing ◽

Low Threshold

During non-rapid eye movement sleep and certain types of anaesthesia, neurons in the neocortex and thalamus exhibit a distinctive slow (<1 Hz) oscillation that consists of alternating UP and DOWN membrane potential states and which correlates with a pronounced slow (<1 Hz) rhythm in the electroencephalogram. While several studies have claimed that the slow oscillation is generated exclusively in neocortical networks and then transmitted to other brain areas, substantial evidence exists to suggest that the full expression of the slow oscillation in an intact thalamocortical (TC) network requires the balanced interaction of oscillator systems in both the neocortex and thalamus. Within such a scenario, we have previously argued that the powerful low-threshold Ca 2+ potential (LTCP)-mediated burst of action potentials that initiates the UP states in individual TC neurons may be a vital signal for instigating UP states in related cortical areas. To investigate these issues we constructed a computational model of the TC network which encompasses the important known aspects of the slow oscillation that have been garnered from earlier in vivo and in vitro experiments. Using this model we confirm that the overall expression of the slow oscillation is intricately reliant on intact connections between the thalamus and the cortex. In particular, we demonstrate that UP state-related LTCP-mediated bursts in TC neurons are proficient in triggering synchronous UP states in cortical networks, thereby bringing about a synchronous slow oscillation in the whole network. The importance of LTCP-mediated action potential bursts in the slow oscillation is also underlined by the observation that their associated dendritic Ca 2+ signals are the only ones that inform corticothalamic synapses of the TC neuron output, since they, but not those elicited by tonic action potential firing, reach the distal dendritic sites where these synapses are located.

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pigkMutation underliesmachobehavior and affects Rohon-Beard cell excitability

Journal of Neurophysiology ◽

10.1152/jn.00355.2015 ◽

2015 ◽

Vol 114 (2) ◽

pp. 1146-1157 ◽

Cited By ~ 2

Author(s):

V. Carmean ◽

M. A. Yonkers ◽

M. B. Tellez ◽

J. R. Willer ◽

G. B. Willer ◽

...

Keyword(s):

Action Potential ◽

Sensory Neurons ◽

Sodium Current ◽

Genetic Defect ◽

Sensory Cells ◽

Loss Of Function ◽

Wild Type ◽

Action Potential Firing ◽

Potential Firing ◽

Touch Response

The study of touch-evoked behavior allows investigation of both the cells and circuits that generate a response to tactile stimulation. We investigate a touch-insensitive zebrafish mutant, macho (maco), previously shown to have reduced sodium current amplitude and lack of action potential firing in sensory neurons. In the genomes of mutant but not wild-type embryos, we identify a mutation in the pigk gene. The encoded protein, PigK, functions in attachment of glycophosphatidylinositol anchors to precursor proteins. In wild-type embryos, pigk mRNA is present at times when mutant embryos display behavioral phenotypes. Consistent with the predicted loss of function induced by the mutation, knock-down of PigK phenocopies maco touch insensitivity and leads to reduced sodium current (INa) amplitudes in sensory neurons. We further test whether the genetic defect in pigk underlies the maco phenotype by overexpressing wild-type pigk in mutant embryos. We find that ubiquitous expression of wild-type pigk rescues the touch response in maco mutants. In addition, for maco mutants, expression of wild-type pigk restricted to sensory neurons rescues sodium current amplitudes and action potential firing in sensory neurons. However, expression of wild-type pigk limited to sensory cells of mutant embryos does not allow rescue of the behavioral touch response. Our results demonstrate an essential role for pigk in generation of the touch response beyond that required for maintenance of proper INa density and action potential firing in sensory neurons.

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The influence of the chloride currents on action potential firing and volume regulation of excitable cells studied by a kinetic model

Journal of Theoretical Biology ◽

10.1016/j.jtbi.2011.01.022 ◽

2011 ◽

Vol 276 (1) ◽

pp. 42-49 ◽

Cited By ~ 3

Author(s):

Nikolaus Berndt ◽

Sabrina Hoffmann ◽

Jan Benda ◽

Hermann-Georg Holzhütter

Keyword(s):

Kinetic Model ◽

Action Potential ◽

Volume Regulation ◽

Excitable Cells ◽

Action Potential Firing ◽

Chloride Currents ◽

Potential Firing

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The input-output relation of primary nociceptive neurons is determined by the morphology of the peripheral nociceptive terminals

10.1101/2020.07.30.228015 ◽

2020 ◽

Author(s):

Omer Barkai ◽

Rachely Butterman ◽

Ben Katz ◽

Shaya Lev ◽

Alexander M. Binshtok

Keyword(s):

Action Potential ◽

Input Output ◽

Pain Sensation ◽

Action Potential Firing ◽

Nociceptive Neurons ◽

Pathological Conditions ◽

Potential Firing ◽

Noxious Stimuli ◽

The Individual ◽

Neuronal Output

AbstractThe output from the peripheral terminals of primary nociceptive neurons, which detect and encode the information regarding noxious stimuli, is crucial in determining pain sensation. The nociceptive terminal endings are morphologically complex structures assembled from multiple branches of different geometry, which converge in a variety of forms to create the terminal tree. The output of a single terminal is defined by the properties of the transducer channels producing the generation potentials and voltage-gated channels, translating the generation potentials into action potential firing. However, in the majority of cases, noxious stimuli activate multiple terminals; thus, the output of the nociceptive neuron is defined by the integration and computation of the inputs of the individual terminals. Here we used a computational model of nociceptive terminal tree to study how the architecture of the terminal tree affects input-output relation of the primary nociceptive neurons. We show that the input-output properties of the nociceptive neurons depend on the length, the axial resistance, and location of individual terminals. Moreover, we show that activation of multiple terminals by capsaicin-like current allows summation of the responses from individual terminals, thus leading to increased nociceptive output. Stimulation of terminals in simulated models of inflammatory or nociceptive hyperexcitability led to a change in the temporal pattern of action potential firing, emphasizing the role of temporal code in conveying key information about changes in nociceptive output in pathological conditions, leading to pain hypersensitivity.Significance statementNoxious stimuli are detected by terminal endings of the primary nociceptive neurons, which are organized into morphologically complex terminal trees. The information from multiple terminals is integrated along the terminal tree, computing the neuronal output, which propagates towards the CNS, thus shaping the pain sensation. Here we revealed that the structure of the nociceptive terminal tree determines the output of the nociceptive neurons. We show that the integration of noxious information depends on the morphology of the terminal trees and how this integration and, consequently, the neuronal output change under pathological conditions. Our findings help to predict how nociceptive neurons encode noxious stimuli and how this encoding changes in pathological conditions, leading to pain.

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