High calcium concentrations reduce cellular excitability of mouse MNTB neurons

Wang, Huimei; Lu, Yong

doi:10.1016/j.brainres.2023.148568

Cited by 5 publications

(1 citation statement)

References 87 publications

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“…Pyramidal cells are among the most commonly studied neocortical neurons ( Spruston, 2008 ), and it is possible that ectopic firing was either ignored or missed because experimental conditions were not sufficient to induce it. For instance, the commonly used artificial cerebrospinal fluid calcium concentration of 2.0 mM could be decreasing cell excitability, which may inhibit EAP generation compared to the physiological 1.2 mM concentration ( Lu et al, 2010 ; Forsberg et al, 2019 ; Wang and Lu, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Activity-dependent ectopic action potentials in regular-spiking neurons of the neocortex

Zhang,

Sapantzi,

Lin

et al. 2023

Front. Cell. Neurosci.

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IntroductionAction potentials usually travel orthodromically along a neuron’s axon, from the axon initial segment (AIS) toward the presynaptic terminals. Under some circumstances action potentials also travel in the opposite direction, antidromically, after being initiated at a distal location. Given their initiation at an atypical site, we refer to these events as “ectopic action potentials.” Ectopic action potentials (EAPs) were initially observed in pathological conditions including seizures and nerve injury. Several studies have described regular-spiking (RS) pyramidal neurons firing EAPs in seizure models. Under nonpathological conditions, EAPs were reported in a few populations of neurons, and our group has found that EAPs can be induced in a large proportion of parvalbumin-expressing interneurons in the neocortex. Nevertheless, to our knowledge there have been no prior reports of ectopic firing in the largest population of neurons in the neocortex, pyramidal neurons, under nonpathological conditions.MethodsWe performed in vitro recordings utilizing the whole-cell patch clamp technique. To elicit EAPs, we triggered orthodromic action potentialswith either long, progressively increasing current steps, or with trains of brief pulses at 30, 60, or 100 Hz delivered in 3 different ways, varying in stimulus and resting period duration.ResultsWe found that a large proportion (72.7%) of neocortical RS cells from mice can fire EAPs after a specific stimulus in vitro, and that most RS cells (56.1%) are capable of firing EAPs across a broad range of stimulus conditions. Of the 37 RS neurons in which we were able to elicit EAPs, it took an average of 863.8 orthodromic action potentials delivered over the course of an average of ~81.4 s before the first EAP was seen. We observed that some cells responded to specific stimulus frequencies while less selective, suggesting frequency tuning in a subset of the cells.DiscussionOur findings suggest that pyramidal cells can integrate information over long time-scales before briefly entering a mode of self-generated firing that originates in distal axons. The surprising ubiquity of EAP generation in RS cells raises interesting questions about the potential roles of ectopic spiking in information processing, cortical oscillations, and seizure susceptibility.

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Section: Introductionmentioning

confidence: 99%

Activity-dependent ectopic action potentials in regular-spiking neurons of the neocortex

Zhang,

Sapantzi,

Lin

et al. 2023

Front. Cell. Neurosci.

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Synaptic facilitation enhances the reliability and precision of high frequency neurotransmission

Bernal-Correa,

Dagostin,

von Gersdorff

et al. 2024

Preprint

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The small and tortuous volume of synaptic clefts limits the diffusion of Ca2+ions during high frequency spiking. Extracellular Ca2+levels ([Ca2+]o) of 0.8 mM or lower have been measured or calculated for different synapses. Here, we recorded evoked postsynaptic potentials (EPSP) and action potentials (AP) from young adult male and female mouse auditory brainstem principal neurons to investigate the relationship between neurotransmission reliability, stimulation frequency and [Ca2+]o. In 0.8 mM [Ca2+]o, we observed AP failures during afferent fiber stimulation at 100 Hz. Surprisingly, AP failures, EPSP-AP latency and jitter were all greatly reduced when stimulation frequency was increased to 500 Hz. Analysis of the EPSP/AP waveform revealed marked facilitation at 500 Hz that was not present at 100 Hz. Raising [Ca2+]oto 1.2 mM or 2.0 mM reduced or eliminated facilitation and, in these conditions, stimulation at 500 Hz increased the number of AP failures. In 0.8 mM [Ca2+]o, afferent fiber stimulation over a broad range of frequencies from 10-1000 Hz produced three different types of spiking responses: Type I cells exhibited band-pass filtering, with best response at approximately 500 Hz, Type II cells exhibited low-pass filtering above 600 Hz, and Type III cells exhibited shallow band-pass filtering centered at approximately 300 Hz. To predict AP success or failure, we built a model based on three factors: size of the EPSP, membrane potential immediately prior to the synaptic event and the number of preceding failures. We conclude that synaptic facilitation can contribute positively to the maintenance of reliable and precise high frequency neurotransmission in the auditory brainstem.

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Evaluation of mechanisms involved in regulation of intrinsic excitability by extracellular calcium in CA1 pyramidal neurons of rat

Forsberg,

Zhou,

Jalali

et al. 2024

Journal of Neurochemistry

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It is well recognized that changes in the extracellular concentration of calcium ions influence the excitability of neurons, yet what mechanism(s) mediate these effects is still a matter of debate. Using patch‐clamp recordings from rat hippocampal CA1 pyramidal neurons, we examined the contribution of G‐proteins and intracellular calcium‐dependent signaling mechanisms to changes in intrinsic excitability evoked by altering the extracellular calcium concentration from physiological (1.2 mM) to a commonly used experimental (2 mM) level. We find that the inhibitory effect on intrinsic excitability of calcium ions is mainly expressed as an increased threshold for action potential firing (with no significant effect on resting membrane potential) that is not blocked by either the G‐protein inhibitor GDPβS or the calcium chelator BAPTA. Our results therefore argue that in the concentration range studied, G‐protein coupled calcium‐sensing receptors, non‐selective cation conductances, and intracellular calcium signaling pathways are not involved in mediating the effect of extracellular calcium ions on intrinsic excitability. Analysis of the derivative of the action potential, dV/dt versus membrane potential, indicates a current shift towards more depolarized membrane potentials at the higher calcium concentration. Our results are thus consistent with a mechanism in which extracellular calcium ions act directly on the voltage‐gated sodium channels by neutralizing negative charges on the extracellular surface of these channels to modulate the threshold for action potential activation.image

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High calcium concentrations reduce cellular excitability of mouse MNTB neurons

Cited by 5 publications

References 87 publications

Activity-dependent ectopic action potentials in regular-spiking neurons of the neocortex

Activity-dependent ectopic action potentials in regular-spiking neurons of the neocortex

Synaptic facilitation enhances the reliability and precision of high frequency neurotransmission

Evaluation of mechanisms involved in regulation of intrinsic excitability by extracellular calcium in CA1 pyramidal neurons of rat

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