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The CA3 neuron exhibits distinct firing modes in response to continuous current injection. (A) Simulated neuronal firing in the CA3 neuron. For smaller amplitude stimulus current, the neuron fires bursts at low frequency (0.0005 nA, 0.015 nA, and 0.02 nA). The burst morphology consistently occurs as a burst of two or more action potentials. With increasing levels of injected stimulus current, the firing becomes regular spiking (0.024 nA). Note that the prominent afterhyperpolarizations observed in experimental recordings are reproduced in the model (Arrows in A). (B) The maximum values of Vm for each spike within a burst (recorded at psuedo-steady-state between 9000 ms and 10000 ms) are shown at each value of injection current I (nA). Vertical dashed lines divide the graph into the four zones. The number in each zone indicates the number of spikes in each burst. (C) The intra-burst frequencies are shown at each value of injection current I (nA). Vertical dashed lines divide the graph into the four zones corresponding to those in B. The number in each zone indicates the number of spikes in each burst.
Source publication
A critical property of some neurons is burst firing, which in the hippocampus plays a primary role in reliable transmission of electrical signals. However, bursting may also contribute to synchronization of electrical activity in networks of neurons, a hallmark of epilepsy. Understanding the ionic mechanisms of bursting in a single neuron, and how...
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Citations
... Bursts can be described as a rapid sequence of action potentials followed by a period of relative quiescence 136,137 , it has been estimated that 95% of pyramidal cells in the macaque monkey CA3 fire in bursts 138,139 . The burst index (BI) is a metric that has been proposed to describe the propensity of burstiness in the firing pattern of neurons, where higher BI values indicate a neuron's higher propensity to fire in bursts. ...
The mammalian hippocampus has been compared to a Global Positioning System (GPS) that enables spatial navigation. This notion has been primarily drawn from studies conducted in nocturnal mammals, such as rats; that lack many adaptations to daylight vision compared to diurnal primates. Here we demonstrate that during foraging in a 3D maze, the common marmoset, a new world diurnal primate with foveal, stereo-color vision, predominantly uses rapid head-gaze shifts to visually explore their surroundings while remaining stationary, and then minimizes head movements to navigate towards goals. On the other hand, rats, mainly move their head at low velocities while locomoting to explore the environment using their whiskers. These differences in exploration-navigation strategies reflect the species' sensory adaptations to different ecological niches. In the marmoset hippocampus CA3/CA1 regions putative pyramidal neurons show selectivity for 3D view, head direction, and less for place, but mainly mixed selectivity for combinations of these variables. Despite weak place selectivity, the spatial position of the animal in the maze can be decoded from the activity of small ensembles of mixed selective neurons. Inhibitory interneurons are tuned to 3D angular head velocity and translation speed, with most cells showing mixed selectivity for both variables. Finally, marmosets lack the rhythmic theta oscillations of local field potentials seen during locomotion in rats. Instead, they show resetting of theta oscillations triggered by head-gaze shifts that co-occurred with the activation of inhibitory interneurons, followed by various modulations in the activity of pyramidal cells. Our results show that the marmoset visual exploration/navigation strategies and the hippocampal neuronal specializations supporting them diverge from those observed in rats, reflecting the far-sensing capabilities of the marmoset visual system adapted to diurnal lifestyle.
... The copyright holder for this preprint (which this version posted May 25, 2023. ; https://doi.org/10.1101/2023.05.24.542209 doi: bioRxiv preprint Bursts can be described as a rapid sequence of action potentials followed by a period of relative quiescence 122,123 , it has been estimated that 95% of pyramidal cells in the macaque monkey CA3 fire in bursts 124,125 . The burst index (BI) is a metric that has been proposed to describe the propensity of burstiness in the firing pattern of neurons, where higher BI values indicate a neuron's higher propensity to fire in bursts. ...
The mammalian hippocampus has been compared to a Global Positioning System (GPS) that enables spatial navigation. This notion has been primarily drawn from studies conducted in nocturnal mammals, such as rats; that lack many adaptations to daylight vision compared to diurnal primates. Here we demonstrate that during foraging in a 3D maze, the common marmoset, a new world diurnal primate with foveal, stereo-color vision, predominantly uses rapid head-gaze shifts while stationary to visually explore their surroundings and then navigates towards goals minimizing head movements. On the other hand, rats, move their head at low velocities while locomoting to explore the environment using their whiskers. These differences in exploration-navigation strategies reflect the two species' sensory adaptations to their ecological niches. In the marmoset hippocampus CA3/CA1 regions putative pyramidal neurons show selectivity for 3D view, head direction, and less for place, but mainly for combinations of these variables. Inhibitory interneurons are tuned to 3D angular head velocity and translation speed, with most cells showing mixed selectivity for both variables. Marmosets lack the rhythmic theta oscillations of local field potentials seen during locomotion in rats. Instead, they show resetting of theta oscillations triggered by head-gaze shifts that co-occurred with the activation of interneurons, followed by various modulations in the activity of pyramidal cells. Our results show that the marmoset visual exploration/navigation strategies and the hippocampal specializations supporting them diverge from those observed in rats, reflecting the far-sensing capabilities of the marmoset adaptations to diurnal vision. Thus, the marmoset hippocampus may be considered a GPS, but G is for gaze.
... Several protocols have been used to trigger CSB, including coincident activation of different synaptic pathways (Bittner et al., 2015;Takahashi & Magee, 2009;Wang et al., 2000;Xu et al., 2012), synchronous synaptic inputs and opposing inhibition (Bastian & Nguyenkim, 2001;Grienberger et al., 2014;Harris et al., 2001;Raus Balind et al., 2019;Royer et al., 2012), coincidence of synaptic inputs and action potentials (Larkum et al., 1999;Magee & Johnston, 1997;Stuart & Hausser, 2001) and somatic and/or dendritic current injections (to elicit intrinsic CSB). A multitude of regulatory mechanisms have been implicated in the emergence of CSB, including dendritic size and arborization (Krichmar et al., 2002;Mainen & Sejnowski, 1996;Narayanan & Chattarji, 2010;van Elburg & van Ooyen, 2010), different combinations of intrinsic properties involved in intrinsic CSB (Cueni et al., 2008;Golding et al., 1999;Hablitz & Johnston, 1981;Hemond et al., 2008;Krahe & Gabbiani, 2004;Lazarewicz et al., 2002;Migliore et al., 1995;Narayanan & Chattarji, 2010;Perez-Reyes, 2003;Raus Balind et al., 2019;Sipila et al., 2006;Su et al., 2001;Swensen & Bean, 2003Tazerart et al., 2008;Traub et al., 1991;Vervaeke et al., 2006;Vickstrom et al., 2020;Williams & Stuart, 1999;Wolfart & Roeper, 2002;Wong & Prince, 1978;Xu & Clancy, 2008;Yue & Yaari, 2004), synaptic properties (Bastian & Nguyenkim, 2001;Grienberger et al., 2014;Harris et al., 2001;Raus Balind et al., 2019;Royer et al., 2012) and astrocytic activation (Ashhad & Narayanan, 2016Condamine et al., 2018;Kadala et al., 2015;Morquette et al., 2015). Although bursts were traditionally studied primarily with reference to reliable transmission of information, selectivity in transmitted information, and synaptic plasticity (Izhikevich et al., 2003;Krahe & Gabbiani, 2004;Lisman, 1997;Metzen et al., 2016;Sakmann, 2017), CSB and associated dendritic plateau potentials have received renewed attention with recent demonstrations that have implicated them in behavioural time scale plasticity (Bittner et al., 2015(Bittner et al., , 2017Magee & Grienberger, 2020;Zhao et al., 2020), perception (Larkum, 2013;Manita et al., 2015;Takahashi et al., 2016Takahashi et al., , 2020, anaesthesia (Aru et al., 2020;Redinbaugh et al., 2020;, active sensing (Lavzin et al., 2012;Ranganathan et al., 2018;Xu et al., 2012) and learning (Doron et al., 2020;Larkum et al., 2022). ...
... To do this, we used the VKM approach (Anirudhan & Narayanan, 2015;Basak & Narayanan, 2018;Mishra & Narayanan, 2021b;Mittal & Narayanan, 2018;Mukunda & Narayanan, 2017;Rathour & Narayanan, 2014;Roy & Narayanan, 2021;Seenivasan & Narayanan, 2020) by repeating CSB protocols on each of the 236 models in the absence of individual ion channels or receptors. Specifically, we individually set the conductances of the eight active ion channels (the NaF and KDR channels were not subjected to VKM analyses to allow AP generation across all VKM models) or NMDAR permeability (Grienberger et al., 2014;Kim et al., 2012;Nunez et al., 1990;Raus Balind et al., 2019;Sipila et al., 2006;Su et al., 2001;Xu & Clancy, 2008) to zero in each valid model that showed valid CSB (Table 3) for the two protocols. We repeated the 900 pA somatic current injection (N CSBV = 187 from Fig. 13A, implying 187 × 8 = 1496 VKMs for eight channels) Fig. 13A, implying 236 × (8 + 1) = 2124 VKMs for eight channels and NMDAR] protocols for eliciting CSB in these models. ...
... A plethora of mechanisms have been implicated in the generation of CSB across different neurons (Ashhad & Narayanan, 2016Bastian & Nguyenkim, 2001;Condamine et al., 2018;Cueni et al., 2008;Hablitz & Johnston, 1981;Hemond et al., 2008;Izhikevich, 2007;Kadala et al., 2015;Krahe & Gabbiani, 2004;Larkum et al., 1999;Lazarewicz et al., 2002;Metzen et al., 2016;Migliore et al., 1995;Morquette et al., 2015;Narayanan & Chattarji, 2010;Perez-Reyes, 2003;Sipila et al., 2006;Stuart & Hausser, 2001;Su et al., 2001;Swensen & Bean, 2003Tazerart et al., 2008;van Elburg & van Ooyen, 2010;Vervaeke et al., 2006;Wang et al., 2000;Williams & Stuart, 1999;Wong & Prince, 1978;Xu & Clancy, 2008;Xu et al., 2012;Yue & Yaari, 2004). Given the widespread expression of these different ion channels, it is important to recognize that these disparate mechanisms need not be mutually exclusive across different neuronal subtypes. ...
Complex spike bursting (CSB) is a characteristic electrophysiological signature exhibited by several neuronal subtypes and has been implicated in neural plasticity, learning, perception, anaesthesia and active sensing. Here, we address how pronounced intrinsic and synaptic heterogeneities affect CSB, with hippocampal CA3 pyramidal neurons (CA3PNs), where CSB emergence and heterogeneities are well characterized, as a substrate. We randomly generated 12,000 unique models and found 236 valid models that satisfied 11 characteristic CA3PN measurements. These morphologically and biophysically realistic valid models accounted for gating kinetics and somatodendritic expression profiles of 10 active ion channels. This heterogeneous population of valid models was endowed with broad distributions of underlying parameters showing weak pairwise correlations. We found two functional subclasses of valid models, intrinsically bursting and regular spiking, with significant differences in the expression of calcium and calcium‐activated potassium conductances. We triggered CSB in all 236 models through different intrinsic or synaptic protocols and observed considerable heterogeneity in CSB propensity and properties spanning models and protocols. Finally, we used virtual knockout analyses and showed that synergistic interactions between intrinsic and synaptic mechanisms regulated CSB emergence and dynamics. Specifically, although there was a dominance of calcium and calcium‐activated potassium channels in the emergence of CSB, individual deletion of none of the several ion channels or N‐methyl‐d‐aspartate receptors resulted in the complete elimination of CSB across all models. Together, our analyses critically implicate ion‐channel degeneracy in the robust emergence of CSB and other characteristic signatures of CA3PNs, despite pronounced heterogeneities in underlying intrinsic and synaptic properties. image
Key points
An unbiased stochastic search algorithm yielded a heterogeneous population of morphologically and biophysically realistic CA3 pyramidal neuronal models matching several signature electrophysiological characteristics.
Two functional subclasses of valid models were identified with intrinsically bursting (IB) and regular spiking (RS) characteristics, which exhibited differential localization within the parametric space with linear and non‐linear dimension reduction analyses.
Calcium and calcium‐activated potassium channels distinguished IB from RS models, apart from playing dominant roles in the emergence of complex spike bursting (CSB).
The impact of deleting individual ion channels or N‐methyl‐d‐aspartate receptors was variable across different models and differential for each channel/receptor, pointing to ion‐channel degeneracy in the emergence of CSB.
Biological heterogeneities across different neurons of the same subtype, ion‐channel degeneracy and state‐dependent changes (involving activity‐dependent plasticity, pathology, and neuromodulation of intrinsic and synaptic properties) need to be considered carefully in assessing the propensity and dynamics of CSB in different neuronal subtypes.
... In bifurcation analysis, we chose three different levels of hyperpolarization-activated dendritic current and used the amplitude of the applied current as a bifurcation parameter (Lippert & Booth, 2009). It is worth noting that the parameter regime for tonic spiking and bursting activity has been investigated in the original Pinsky-Rinzel model (Atherton et al., 2016;Hahn & Durand, 2001;Kepecs & Wang, 2000;Pinsky & Rinzel, 1994;Xu & Clancy, 2008), but a dynamic complexity for the two-compartment neuron model with hyperpolarization-activated dendritic current modulation has not yet been reported. In addition, we examined the spectral content of noise perturbations, which is related to the behavior of SR, and highlight the beneficial role of biphasic pulse trains over broadband OU noise. ...
In vitro studies have shown that hippocampal pyramidal neurons employ a mechanism similar to stochastic resonance (SR) to enhance the detection and transmission of weak stimuli generated at distal synapses. To support the experimental findings from the perspective of multicompartment model analysis, this paper aimed to elucidate the phenomenon of SR in a noisy two-compartment hippocampal pyramidal neuron model, which was a variant of the Pinsky-Rinzel neuron model with smooth activation functions and a hyperpolarization-activated cation current. With a bifurcation analysis of the model, we demonstrated the underlying dynamical structure responsible for the occurrence of SR. Furthermore, using a stochastically generated biphasic pulse train and broadband noise generated by the Orenstein-Uhlenbeck process as noise perturbation, both SR and suprathreshold SR were observed and quantified. Spectral analysis revealed that the distribution of spectral power under noise perturbations, in addition to inherent neurodynamics, is the main factor affecting SR behavior. The research results suggested that noise enhances the transmission of weak stimuli associated with elongated dendritic structures of hip-pocampal pyramidal neurons, thereby providing support for related laboratory findings.
... The present study is to our knowledge the first that investigated the involvement of T-type calcium channels in gamma oscillations. T-type channels are low-voltage-activated channels that open near the foot of an action potential and play an important role in the generation of the afterdepolarizing potential and burst firing in CA3 pyramidal neurons, resulting in increased excitability of the cells (Xu and Clancy, 2008). Thus, the opening of these channels during cholinergic stimulation could be involved in the generation or maintenance of gamma oscillations. ...
... Thus, the opening of these channels during cholinergic stimulation could be involved in the generation or maintenance of gamma oscillations. However, an enhanced calcium influx through an exogenous opening of T-type calcium channels, as seen after the application of SAK3, might activate K Ca channels terminating the excitability of cells (Xu and Clancy, 2008) within the gamma circuit and decrease the power. Our results also show that a blockade of T-type channels increases the peak frequency of oscillations. ...
Ion channels activated around the subthreshold membrane potential determine the likelihood of neuronal firing in response to synaptic inputs, a process described as intrinsic neuronal excitability. Long-term plasticity of chemical synaptic transmission is traditionally considered the main cellular mechanism of information storage in the brain; however, voltage- and calcium-activated channels modulating the inputs or outputs of neurons are also subjects of plastic changes and play a major role in learning and memory formation. Gamma oscillations are associated with numerous higher cognitive functions such as learning and memory, but our knowledge of their dependence on intrinsic plasticity is by far limited. Here we investigated the roles of potassium and calcium channels activated at near subthreshold membrane potentials in cholinergically induced persistent gamma oscillations measured in the CA3 area of rat hippocampal slices. Among potassium channels, which are responsible for the afterhyperpolarization in CA3 pyramidal cells, we found that blockers of SK (K Ca 2) and K V 7.2/7.3 (KCNQ2/3), but not the BK (K Ca 1.1) and IK (K Ca 3.1) channels, increased the power of gamma oscillations. On the contrary, activators of these channels had an attenuating effect without affecting the frequency. Pharmacological blockade of the low voltage-activated T-type calcium channels (Ca V 3.1–3.3) reduced gamma power and increased the oscillation peak frequency. Enhancement of these channels also inhibited the peak power without altering the frequency of the oscillations. The presented data suggest that voltage- and calcium-activated ion channels involved in intrinsic excitability strongly regulate the power of hippocampal gamma oscillations. Targeting these channels could represent a valuable pharmacological strategy against cognitive impairment.
... These neuron circuits (NFF) have been found in the prefrontal cortex (PFC) (Compte Albert, 2006;Fellous et al. 2003) and could also be probably found in the CA1 or CA3 nuclei of the hippocampus where endogenous oscillations have been found (Jochems et al. 2013;Pinsky et al. 1994;Xu et al. 2008), the hippocampus entorhinal cortex (EC) and amygdala (Egorov et al., 2006) and very likely on the dentate gyrus (DG) which has neurons whose spiking pattern is of type NASP (Non-Adapting Spiking) as classified by the Hippocampome project (Komendantov et al. 2019;Hippocampome). These DG neurons exhibit the closest spiking pattern matching the results of our simulations. ...
In this research we explore in detail how a phenomenon called “sustained persistent activity” is achieved by circuits of interconnected neurons. Persistent activity is a phenomenon that has been extensively studied (Papoutsi et al. 2013; Kaminski et. al. 2017; McCormick et al. 2003; Rahman, and Berger, 2011). Persistent activity consists of neuron circuits whose spiking activity remains even after the initial stimuli are removed. Persistent activity has been found in the prefrontal cortex (PFC) and has been correlated to working memory and decision making (Clayton E. Curtis and Daeyeol Lee, 2010).
We go beyond the explanation of how persistent activity happens and show how arrangements of those basic circuits encode and store data and are used to perform more elaborated tasks and computations.
The purpose of the model we propose here is to describe the minimum number of neurons and their interconnections required to explain persistent activity and how this phenomenon is actually a fast storage mechanism required for implementing working memory, task processing and decision making.
... CaV3.3) that are the primary contributors to bursting in thalamic cells (Anderson et al., 2005;Astori et al., 2011;Cain et al., 2018;Dreyfus et al., 2010;Kim et al., 2001;Talley et al., 1999) (Wei et al., 2011). A higher ratio of CaV3.2 to CaV3.1 channels could contribute to making HO bursts distinct due to slight differences in channel dynamics (Cain & Snutch, 2010;Kozlov et al., 1999;Xu & Clancy, 2008). Overall, the evidence points to a stronger T-channelmediated conductance in HO nuclei and VP, and future experiments could test the contribution of specific channels, as more precise T-channel blockers become available (Choe et al., 2011). ...
Thalamic neurons fire spikes in two modes, burst and tonic. The function of burst firing is unclear, but the evidence suggests that bursts are more effective at activating cortical cells, and that post‐inhibition rebound bursting contributes to thalamocortical oscillations during sleep. Bursts are considered stereotyped signals; however, there is limited evidence regarding how burst properties compare across thalamic nuclei of different functional or anatomical organization. Here we used whole‐cell patch clamp recordings and compartmental modeling: to investigate the properties of bursts in six sensory thalamic nuclei, to study the mechanisms that can lead to different burst properties, and to assess the implications of different burst properties for thalamocortical transmission and oscillatory functions. We found that bursts in higher order cells on average had higher number of spikes and longer latency to the first spike. Additionally, burst features in first order neurons were determined by sensory modality. Shifting the voltage‐dependence and density of the T‐channel conductance in a compartmental model replicates the burst properties from the intracellular recordings, pointing to molecular mechanisms that can generate burst diversity. Furthermore, the model predicts that bursts with higher number of spikes will drastically reduce the effectiveness of thalamocortical transmission. In addition, the latency to burst limited the rebound oscillatory frequency in modeled cells. These results demonstrate that burst properties vary according to the thalamocortical hierarchy and with sensory modality. The findings imply that, while in burst mode, thalamocortical transmission and firing frequency will be determined by the number of spikes and latency to burst.
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... On the other hand, the suppressive effect of LFS on spike firing and ADP amplitude enhancement may be accomplished by inhibiting the kindling effect on these currents. A number of voltage-activated conductance are likely to shape the ADP, including slowly deactivating K + currents (such as M current) (Yue and Yaari, 2004), the hyperpolarization-activated H current, and possibly small T-type Ca 2+ currents (Xu and Clancy, 2008). Thus, it is necessary to study the changes in the activity and/or expression of some probable specific HVA or low-voltageactivated (LVA) Ca 2+ ion channels which may be involved. ...
Low-frequency stimulation has demonstrated promising seizure suppression in animal models of epilepsy, while the mechanism of the effect is still debated. Changes in intrinsic properties have been recognized as a prominent pathophysiologically relevant feature of numerous neurological disorders including epilepsy. Here, it was evaluated whether LFS can preserve the intrinsic neuronal electrophysiological properties in a rat model of epilepsy, focusing on the possible involvement of voltage-gated Ca ²⁺ channels. The amygdala kindling model was induced by 3 s monophasic square wave pulses (50 Hz, 1 ms duration, 12times/day at 5 min intervals). Both LFS alone and kindled plus LFS (KLFS) groups received four packages of LFS (each consisting of 200 monophasic square pulses, 0.1 ms pulse duration at 1 Hz with the after discharge threshold intensity), which in KLFS rats was applied immediately after kindling induction. Whole-cell patch-clamp recordings were made in the presence of fast synaptic blockers 24 h after the last kindling stimulations or following kindling stimulations plus LFS application. In the KLFS group, both the rebound excitation and kindling-induced intrinsic hyperexcitability were decreased, associated with a regular intrinsic firing as indicated by a lower coefficient of variation. The amplitude of afterdepolarization (ADP) and its area under the curve were both decreased in the KLFS group compared to the kindled group. LFS prevented the increasing effect of kindling on Ca ²⁺ currents in the KLFS group. Findings provided evidence for a novel form of epileptiform activity suppression by LFS in the presence of synaptic blockade possibly by decreasing Ca ²⁺ currents.
... To evaluate how autaptic changes influence the pattern of bursting firing, a theoretical model of bursting firing of action potentials (APs) was adapted from previous work [16,17]. The XC model is based primarily on biophysical properties of hippocampal CA3 pyramidal neurons and comprises the delayedrectifier K + current, the transient K + current, the Ca 2+ -activated K + current, the Na + current, and the Ca 2+ current. ...
... In the present simulations, the conductance values and reversal potentials used to solve the set of differential equations are listed in Table 1. Detailed descriptions of XC modeled neuron were provided previously [16,17]. Moreover, a chemical autapse, which used the fast threshold modulation scheme [18,19], was incorporated into the modeled neuron in attempts to mimic the Rot effects observed in mHippoE-14 cells. ...
... Simulated bursting pattern of APs in XC modeled neuron with varying g aut In a final set of study, we explored how the dynamics of bursting firing in a modeled neuron can be altered by increasing the values of g aut to mimic the effects of Rot on I aut described above. The descriptions for this modeled neuron were detailed previously [16,17] and an autaptic synapse with varying strength was incorporated into the model [18,19]. The g aut value reflects the autaptic self-feedback strength and other default parameters are Table 1. ...
Background/aims:
Rotenone (Rot) is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored.
Methods:
With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated.
Results:
Addition of Rot produced an inhibitory action on the peak amplitude of INa with an IC50 value of 39.3 µM; however, neither activation nor inactivation kinetics of INa was changed during cell exposure to this compound. Addition of Rot produced little or no modifications in the steady-state inactivation curve of INa. Rot increased the amplitude of Ca2+-activated Cl- current in response to membrane depolarization with an EC50 value of 35.4 µM; further addition of niflumic acid reversed Rot-mediated stimulation of this current. Moreover, when these cells were exposed to 10 µM Rot, a specific population of ATP-sensitive K+ channels with a single-channel conductance of 18.1 pS was measured, despite its inability to alter single-channel conductance. Under current clamp condition, the frequency of miniature end-plate potentials in mHippoE-14 cells was significantly raised in the presence of Rot (10 µM) with no changes in their amplitude and time course of rise and decay. In simulated model of hippocampal neurons incorporated with chemical autaptic connection, increased autaptic strength to mimic the action of Rot was noted to change the bursting pattern with emergence of subthreshold potentials.
Conclusions:
The Rot effects presented herein might exert a significant action on functional activities of hippocampal neurons occurring in vivo.
... LVA Cay3.x channels also inactivate at a fast rate. Thus, a combination of low threshold of activationwith fast inactivation kinetics results in transient Ct* influx, giving rise to the so-called "low-threshold Caz* potentials," which initiate the burstfiring process (Ciin and Snutch 2010;Contreras 2006;Jahnsen and Llinas 1984;Lee et al. 2003;Yazdi et al. 2007;Xu and Clancy 2008). The burst-firing mode in the CNS conributes to the generation of physiological events such as sleep spindles, and pathological conditions such as epileptic seizures (Cain and Snutch 2010, zAlD.ln ...
Voltage-sensitive Ca²⁺ (CaV) channels are the primary route of depolarization-induced Ca²⁺ entry in neurons and other excitable cells, leading to an increase in intracellular Ca²⁺ concentration ([Ca²⁺]i). The resulting increase in [Ca²⁺]i activates a wide range of Ca²⁺-dependent processes in neurons, including neurotransmitter release, gene transcription, activation of Ca²⁺-dependent enzymes, and activation of certain K⁺ channels and chloride channels. In addition to their key roles under physiological conditions, CaV channels are also an important target of alcohol, and alcohol-induced changes in Ca²⁺ signaling can disturb neuronal homeostasis, Ca²⁺-mediated gene transcription, and the function of neuronal circuits, leading to various neurological and/or neuropsychiatric symptoms and disorders, including alcohol withdrawal induced–seizures and alcoholism.
