scholarly journals Complex dynamics in simplified neuronal models: reproducing Golgi cell electroresponsiveness

2018 ◽  
Author(s):  
Alice Geminiani ◽  
Claudia Casellato ◽  
Francesca Locatelli ◽  
Francesca Prestori ◽  
Alessandra Pedrocchi ◽  
...  
Keyword(s):  
Critical Role ◽  
Spike Frequency ◽  
Neuronal Membrane ◽  
Model Parameters ◽  
Dimensional System ◽  
Spike Frequency Adaptation ◽  
Phase Reset ◽  
Golgi Cell ◽  
Subthreshold Oscillations ◽  
Frequency Adaptation

AbstractBrain neurons exhibit complex electroresponsive properties - including intrinsic subthreshold oscillations and pacemaking, resonance and phase-reset - which are thought to play a critical role in controlling neural network dynamics. Although these properties emerge from detailed representations of molecular-level mechanisms in “realistic” models, they cannot usually be generated by simplified neuronal models (although these may show spike-frequency adaptation and bursting). We report here that this whole set of properties can be generated by theextended generalized leaky integrate-and-fire(E-GLIF) neuron model. E-GLIF derives from the GLIF model family and is therefore mono-compartmental, keeps the limited computational load typical of a linear low-dimensional system, admits analytical solutions and can be tuned through gradient-descent algorithms. Importantly, E-GLIF is designed to maintain a correspondence between model parameters and neuronal membrane mechanisms through a minimum set of equations. In order to test its potential, E-GLIF was used to model a specific neuron showing rich and complex electroresponsiveness, the cerebellar Golgi cell, and was validated against experimental electrophysiological data recorded from Golgi cells in acute cerebellar slices. During simulations, E-GLIF was activated by stimulus patterns, including current steps and synaptic inputs, identical to those used for the experiments. The results demonstrate that E-GLIF can reproduce the whole set of complex neuronal dynamics typical of these neurons - including intensity-frequency curves, spike-frequency adaptation, depolarization-induced and post-inhibitory rebound bursting, spontaneous subthreshold oscillations, resonance and phase-reset, - providing a new effective tool to investigate brain dynamics in large-scale simulations.

scholarly journals Absence of Pannexin 1 Stabilizes Hippocampal Excitability After Intracerebral Treatment With Aβ (1-42) and Prevents LTP Deficits in Middle-Aged Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Nicolina Südkamp ◽  
Olena Shchyglo ◽  
Denise Manahan-Vaughan
Keyword(s):  
Neuronal Excitability ◽  
Long Term Potentiation ◽  
Firing Frequency ◽  
Spike Frequency ◽  
Synaptic Function ◽  
Membrane Properties ◽  
Neuronal Membrane ◽  
Spike Frequency Adaptation ◽  
Control Peptide ◽  
Frequency Adaptation

Beta-amyloid protein [Aβ(1-42)] plays an important role in the disease progress and pathophysiology of Alzheimer's disease (AD). Membrane properties and neuronal excitability are altered in the hippocampus of transgenic AD mouse models that overexpress amyloid precursor protein. Although gap junction hemichannels have been implicated in the early pathogenesis of AD, to what extent Pannexin channels contribute to Aβ(1-42)-mediated brain changes is not yet known. In this study we, therefore, investigated the involvement of Pannexin1 (Panx1) channels in Aβ-mediated changes of neuronal membrane properties and long-term potentiation (LTP) in an animal model of AD. We conducted whole-cell patch-clamp recordings in CA1 pyramidal neurons 1 week after intracerebroventricular treatments of adult wildtype (wt) and Panx1 knockout (Panx1-ko) mice with either oligomeric Aβ(1-42), or control peptide. Panx1-ko hippocampi treated with control peptide exhibited increased neuronal excitability compared to wt. In addition, action potential (AP) firing frequency was higher in control Panx1-ko slices compared to wt. Aβ-treatment reduced AP firing frequency in both cohorts. But in Aβ-treated wt mice, spike frequency adaptation was significantly enhanced, when compared to control wt and to Aβ-treated Panx1-ko mice. Assessment of hippocampal LTP revealed deficits in Aβ-treated wt compared to control wt. By contrast, Panx1-ko exhibited LTP that was equivalent to LTP in control ko hippocampi. Taken together, our data show that in the absence of Pannexin1, hippocampi are more resistant to the debilitating effects of oligomeric Aβ. Both Aβ-mediated impairments in spike frequency adaptation and in LTP that occur in wt animals, are ameliorated in Panx1-ko mice. These results suggest that Panx1 contributes to early changes in hippocampal neuronal and synaptic function that are triggered by oligomeric Aβ.

scholarly journals Kisspeptin inhibits a slow afterhyperpolarization current via protein kinase C and reduces spike frequency adaptation in GnRH neurons

2013 ◽  
Vol 304 (11) ◽  
pp. E1237-E1244 ◽  
Author(s):  
Chunguang Zhang ◽  
Oline K. Rønnekleiv ◽  
Martin J. Kelly
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Transient Receptor Potential ◽  
Critical Role ◽  
Transient Receptor Potential Channels ◽  
Spike Frequency ◽  
Spike Frequency Adaptation ◽  
Kinase C ◽  
Frequency Adaptation ◽  
Gnrh Neurons

Kisspeptin signaling via its cognate receptor G protein-coupled receptor 54 (GPR54) in gonadotropin-releasing hormone (GnRH) neurons plays a critical role in regulating pituitary secretion of luteinizing hormone and thus reproductive function. GPR54 is Gq-coupled to activation of phospholipase C and multiple second messenger signaling pathways. Previous studies have shown that kisspeptin potently depolarizes GnRH neurons through the activation of canonical transient receptor potential channels and inhibition of inwardly rectifying K+ channels to generate sustained firing. Since the initial studies showing that kisspeptin has prolonged effects, the question has been why is there very little spike frequency adaption during sustained firing? Presently, we have discovered that kisspeptin reduces spike frequency adaptation and prolongs firing via the inhibition of a calcium-activated slow afterhyperpolarization current ( IsAHP). GnRH neurons expressed two distinct IsAHP, a kisspeptin-sensitive and an apamin-sensitive IsAHP. Essentially, kisspeptin inhibited 50% of the IsAHP and apamin inhibited the other 50% of the current. Furthermore, the kisspeptin-mediated inhibition of IsAHP was abrogated by the protein kinase C (PKC) inhibitor calphostin C, and the PKC activator phorbol 12,13-dibutyrate mimicked and occluded any further effects of kisspeptin on IsAHP. The protein kinase A (PKA) inhibitors H-89 and the Rp diastereomer of adenosine 3′,5′-cyclic monophosphorothioate had no effect on the kisspeptin-mediated inhibition but were able to abrogate the inhibitory effects of forskolin on the IsAHP, suggesting that PKA is not involved. Therefore, in addition to increasing the firing rate through an overt depolarization, kisspeptin can also facilitate sustained firing through inhibiting an apamin-insensitive IsAHP in GnRH neurons via a PKC.

Morphological and Electrophysiological Properties of Principal Neurons in the Rat Lateral Amygdala In Vitro

2001 ◽  
Vol 85 (2) ◽  
pp. 714-723 ◽  
Author(s):  
E.S.L. Faber ◽  
R. J. Callister ◽  
P. Sah
Keyword(s):  
Cell Morphology ◽  
Brain Slices ◽  
Spike Trains ◽  
Spike Frequency ◽  
Morphological Properties ◽  
Spike Frequency Adaptation ◽  
Differential Distribution ◽  
Lateral Amygdala ◽  
Frequency Adaptation ◽  
Firing Properties

In this study, we characterize the electrophysiological and morphological properties of spiny principal neurons in the rat lateral amygdala using whole cell recordings in acute brain slices. These neurons exhibited a range of firing properties in response to prolonged current injection. Responses varied from cells that showed full spike frequency adaptation, spiking three to five times, to those that showed no adaptation. The differences in firing patterns were largely explained by the amplitude of the afterhyperpolarization (AHP) that followed spike trains. Cells that showed full spike frequency adaptation had large amplitude slow AHPs, whereas cells that discharged tonically had slow AHPs of much smaller amplitude. During spike trains, all cells showed a similar broadening of their action potentials. Biocytin-filled neurons showed a range of pyramidal-like morphologies, differed in dendritic complexity, had spiny dendrites, and differed in the degree to which they clearly exhibited apical versus basal dendrites. Quantitative analysis revealed no association between cell morphology and firing properties. We conclude that the discharge properties of neurons in the lateral nucleus, in response to somatic current injections, are determined by the differential distribution of ionic conductances rather than through mechanisms that rely on cell morphology.

Spike frequency adaptation studied in hypoglossal motoneurons of the rat

1995 ◽  
Vol 73 (5) ◽  
pp. 1799-1810 ◽  
Author(s):  
A. Sawczuk ◽  
R. K. Powers ◽  
M. D. Binder
Keyword(s):  
Steady State ◽  
Time Course ◽  
Firing Frequency ◽  
Spike Frequency ◽  
Membrane Properties ◽  
Repetitive Firing ◽  
Hypoglossal Nucleus ◽  
Spike Frequency Adaptation ◽  
Frequency Adaptation ◽  
Three Phases

1. We studied spike frequency adaptation of motoneuron discharge in the rat hypoglossal nucleus using a brain stem slice preparation. The characteristics of adaptation in response to long (60 s) injected current steps were qualitatively similar to those observed previously in cat hindlimb motoneurons. The discharge rate typically exhibited a rapid initial decline, characterized by a linear frequency-time relation, followed by a gradual exponential decline that continued for the duration of current injection. However, a more systematic, quantitative analysis of the data revealed that there were often three distinct phases of the adaptation rather than two. 2. The three phases of adaptation (initial, early, and late) were present in at least one 60-s trial of repetitive firing in all but a small number of motoneurons. Initial adaptation was limited to the first few spikes except in a few trials (7%) in which there was no initial adaptation. The time course of the subsequent decline in rate could be adequately described by a single-exponential function in about half of the trials (48%). In the remaining trials this subsequent decline in frequency was better described as the sum of two exponential functions: an early phase, lasting < 2 s, and a late phase, which lasted for the duration of the discharge period. 3. The magnitude of initial adaptation was correlated with the initial firing frequency (i.e., the reciprocal of the 1st interspike interval). The magnitudes of the early and late phases of adaptation were correlated with the firing frequency reached at the end of initial adaptation. Neither the magnitudes nor the time courses of the three phases were correlated with other membrane properties such as input resistance, rheobase, or repetitive firing threshold. 4. The slope of the frequency-current (f-I) curve was steeper in the initial phase (first 2-5 spikes) than in either the early (< 2 s) or late (> 2 s) phases of adaptation as previously reported by other investigators. In the absence of early adaptation, a steady state for the f-I slope was reached by 0.7-1 s, the time typically reported in studies of repetitive discharge. However, when early adaptation was present (50% of the trials), a steady-state value for the f-I slope was not reached until the cell had discharged for > 1 s. 5. To characterize the time course of firing rate recovery from the adaptive processes, the current was turned off for periods of < or = 10 s during the course of a 60-s trial.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Selective attenuation of Ether-a-go-go related K+ currents by endogenous acetylcholine reduces spike-frequency adaptation and network correlation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Edward D Cui ◽  
Ben W Strowbridge
Keyword(s):  
Late Phase ◽  
Pyramidal Cells ◽  
Spike Frequency ◽  
Spike Frequency Adaptation ◽  
Firing Rates ◽  
Frequency Adaptation ◽  
Rat Neocortex ◽  
Persistent Firing ◽  
K Current

Most neurons do not simply convert inputs into firing rates. Instead, moment-to-moment firing rates reflect interactions between synaptic inputs and intrinsic currents. Few studies investigated how intrinsic currents function together to modulate output discharges and which of the currents attenuated by synthetic cholinergic ligands are actually modulated by endogenous acetylcholine (ACh). In this study we optogenetically stimulated cholinergic fibers in rat neocortex and find that ACh enhances excitability by reducing Ether-à-go-go Related Gene (ERG) K+ current. We find ERG mediates the late phase of spike-frequency adaptation in pyramidal cells and is recruited later than both SK and M currents. Attenuation of ERG during coincident depolarization and ACh release leads to reduced late phase spike-frequency adaptation and persistent firing. In neuronal ensembles, attenuating ERG enhanced signal-to-noise ratios and reduced signal correlation, suggesting that these two hallmarks of cholinergic function in vivo may result from modulation of intrinsic properties.

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