scholarly journals ICAN (TRPM4) Contributes to the Intrinsic Excitability of Prefrontal Cortex Layer 2/3 Pyramidal Neurons

2021 ◽  
Vol 22 (10) ◽  
pp. 5268
Author(s):  
Francisco Andres Peralta ◽  
Denise Andres Riquelme ◽  
Franco Dario Navarro ◽  
Claudio Moreno ◽  
Elias Leiva-Salcedo
Keyword(s):  
Prefrontal Cortex ◽  
Membrane Potential ◽  
High Frequency ◽  
Pyramidal Neurons ◽  
Intrinsic Excitability ◽  
High Frequency Stimulation ◽  
Dependent Manner ◽  
Calcium Dependent ◽  
Layer 2 ◽  
Frequency Stimulation

Pyramidal neurons in the medial prefrontal cortical layer 2/3 are an essential contributor to the cellular basis of working memory; thus, changes in their intrinsic excitability critically affect medial prefrontal cortex (mPFC) functional properties. Transient Receptor Potential Melastatin 4 (TRPM4), a calcium-activated nonselective cation channel (CAN), regulates the membrane potential in a calcium-dependent manner. In this study, we uncovered the role of TRPM4 in regulating the intrinsic excitability plasticity of pyramidal neurons in the mouse mPFC layer of 2/3 using a combination of conventional and nystatin perforated whole-cell recordings. Interestingly, we found that TRPM4 is open at resting membrane potential, and its inhibition increases input resistance and hyperpolarizes membrane potential. After high-frequency stimulation, pyramidal neurons increase a calcium-activated non-selective cation current, increase the action potential firing, and the amplitude of the afterdepolarization, these effects depend on intracellular calcium. Furthermore, pharmacological inhibition or genetic silencing of TRPM4 reduces the firing rate and the afterdepolarization after high frequency stimulation. Together, these results show that TRPM4 plays a significant role in the excitability of mPFC layer 2/3 pyramidal neurons by modulating neuronal excitability in a calcium-dependent manner.

scholarly journals L-Type Calcium Channels Are Required for One Form of Hippocampal Mossy Fiber LTP

1998 ◽  
Vol 79 (4) ◽  
pp. 2181-2190 ◽  
Author(s):  
Ajay Kapur ◽  
Mark F. Yeckel ◽  
Richard Gray ◽  
Daniel Johnston
Keyword(s):  
Calcium Channels ◽  
High Frequency ◽  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Calcium Influx ◽  
Calcium Transients ◽  
High Frequency Stimulation ◽  
Frequency Stimulation ◽  
Ca3 Pyramidal Neurons ◽  
Postsynaptic Calcium

Kapur, Ajay, Mark F. Yeckel, Richard Gray, and Daniel Johnston. L-type calcium channels are required for one form of hippocampal mossy fiber LTP. J. Neurophysiol. 79: 2181–2190, 1998. The requirement of postsynaptic calcium influx via L-type channels for the induction of long-term potentiation (LTP) of mossy fiber input to CA3 pyramidal neurons was tested for two different patterns of stimulation. Two types of LTP-inducing stimuli were used based on the suggestion that one of them, brief high-frequency stimulation (B-HFS), induces LTP postsynaptically, whereas the other pattern, long high-frequency stimulation (L-HFS), induces mossy fiber LTP presynaptically. To test whether or not calcium influx into CA3 pyramidal neurons is necessary for LTP induced by either pattern of stimulation, nimodipine, a L-type calcium channel antagonist, was added during stimulation. In these experiments nimodipine blocked the induction of mossy fiber LTP when B-HFS was given [34 ± 5% (mean ± SE) increase in control versus 7 ± 4% in nimodipine, P < 0.003]; in contrast, nimodipine did not block the induction of LTP with L-HFS (107 ± 10% in control vs. 80 ± 9% in nimodipine, P > 0.05). Administration of nimodipine after the induction of LTP had no effect on the expression of LTP. In addition, B- and L-HFS delivered directly to commissural/associational fibers in stratum radiatum failed to induce a N-methyl-d-aspartate-independent form of LTP, obviating the possibility that the presumed mossy fiber LTP resulted from potentiation of other synapses. Nimodipine had no effect on calcium transients recorded from mossy fiber presynaptic terminals evoked with the B-HFS paradigm but reduced postsynaptic calcium transients. Our results support the hypothesis that induction of mossy fiber LTP by B-HFS is mediated postsynaptically and requires entry of calcium through L-type channels into CA3 neurons.

scholarly journals High frequency stimulation-induced plasticity in the prelimbic cortex of rats emerges during adolescent development and is associated with an increase in dopamine receptor function

2018 ◽  
Author(s):  
Shuo Kang ◽  
C. Lee Cox ◽  
Joshua Michael Gulley
Keyword(s):  
Dopamine Receptor ◽  
Adolescent Development ◽  
High Frequency ◽  
D2 Receptor ◽  
Field Potential ◽  
High Frequency Stimulation ◽  
Dependent Manner ◽  
Prelimbic Cortex ◽  
Sprague Dawley ◽  
Frequency Stimulation

Recent studies in rats suggest that high frequency stimulation (HFS) in the ventral hippocampus induces long-term depression (LTD) in the deep layer of the medial prefrontal cortex (mPFC), but only after the prefrontal GABA system has sufficiently developed during early- to mid-adolescence. It is not clear whether this LTD is specific to the hippocampus-mPFC circuit or is instead an intrinsitc regulatory mechanism for the developed mPFC neuro-network. The potential mechanisms underlying this HFS-induced LTD are also largely unknown. In the current study, naïve male Sprague Dawley rats were sacrificed during peri-adolescence or young adulthood for in vitro extracellular recording to determine if HFS delivered in the prelimbic cortex (PLC) would induce LTD in an age-dependent manner and if dopamine receptors are involved in the expression of this LTD. We found four trains of stimulation at 50 Hz induced an LTD in the PFC of adult, but not peri-adolescent, rats. This LTD required intact GABAA receptor functioning and could also be blocked by dopamine D1 or D2 receptor antagonists. Bath application of selective D1 or D2 receptor agonists produced a significant facilitation or suppression in the field potential, respectively, and these effects were only observed in the adult PLC. Furthermore, neither D1 nor D2 stimualtion prior to HFS was able to facilitate LTD in the peri-adolescent PLC. Together, these results suggest dopamine receptor functionality in the PLC increases during adolescent development and it plays an important role in this late-maturating form of plasticity.

Effect of Intermittent High Frequency Stimulation on Muscle Velocity Recovery Cycle Recordings

2021 ◽  
Author(s):  
Annie Hochstrasser ◽  
Belén Rodriguez ◽  
Nicole Söll ◽  
Hugh Bostock ◽  
Werner J Z'Graggen
Keyword(s):  
Membrane Potential ◽  
Endurance Training ◽  
High Frequency ◽  
Peak Force ◽  
Muscle Membrane ◽  
High Frequency Stimulation ◽  
Recovery Cycle ◽  
Frequency Stimulation ◽  
Interstimulus Intervals ◽  
The Impact

The technique of multi-fiber muscle velocity recovery cycle recordings was developed as a diagnostic tool to assess muscle membrane potential changes and ion channel function in vivo. This study was undertaken to assess the impact of intermittent high frequency stimulation on muscle velocity recovery cycle components, and to study whether the changes can be modified by endurance training. We recorded muscle velocity recovery cycles with 1 and 2 conditioning stimuli in the left tibialis anterior muscle in 15 healthy subjects during intermittent 37 Hz stimulation and analyzed its effects on the different phases of supernormality. Recordings were conducted before and after two weeks endurance training. Training effect was assessed by measuring the difference in endurance time, peak force and limb circumference. Muscle velocity recovery cycle recordings during intermittent high frequency stimulation were successfully recorded in 12 subjects. Supernormality for interstimulus intervals shorter than 15 ms (early supernormality) was maximally reduced at the beginning of repetitive stimulation and recovered during stimulation. Supernormality for interstimulus intervals between 50 and 150 ms (late supernormality) showed a delayed decrease and stayed significantly reduced after high frequency stimulation. Training had no significant effect on any of the measured parameters, but we found that training induced changes in peak force correlated positively with baseline changes of early supernormality. Our results support the hypothesis that early supernormality represents membrane potential, which depolarizes in the beginning of high frequency stimulation. Late supernormality probably reflects transverse tubular function and shows progressive changes during high frequency stimulation with delayed normalization.

Cellular Mechanisms Underlying Antiepileptic Effects of Low- and High-Frequency Electrical Stimulation in Acute Epilepsy in Neocortical Brain Slices In Vitro

2007 ◽  
Vol 97 (3) ◽  
pp. 1887-1902 ◽  
Author(s):  
Yitzhak Schiller ◽  
Yael Bankirer
Keyword(s):  
Electrical Stimulation ◽  
High Frequency ◽  
Brain Slices ◽  
Low Frequency ◽  
High Frequency Stimulation ◽  
Dependent Manner ◽  
Cellular Mechanisms ◽  
Epileptiform Discharges ◽  
Frequency Stimulation

Approximately 30% of epilepsy patients suffer from drug-resistant epilepsy. Direct electrical stimulation of the epileptogenic zone is a potential new treatment modality for this devastating disease. In this study, we investigated the effect of two electrical stimulation paradigms, sustained low-frequency stimulation and short trains of high-frequency stimulation, on epileptiform discharges in neocortical brain slices treated with either bicuculline or magnesium-free extracellular solution. Sustained low-frequency stimulation (5–30 min of 0.1- to 5-Hz stimulation) prevented both interictal-like discharges and seizure-like events in an intensity-, frequency-, and distance-dependent manner. Short trains of high-frequency stimulation (1–5 s of 25- to 200-Hz stimulation) prematurely terminated seizure-like events in a frequency-, intensity-, and duration-dependent manner. Roughly one half the seizures terminated within the 100-Hz stimulation train ( P < 0.01 compared with control), whereas the remaining seizures were significantly shortened by 53 ± 21% ( P < 0.01). Regarding the cellular mechanisms underlying the antiepileptic effects of electrical stimulation, both low- and high-frequency stimulation markedly depressed excitatory postsynaptic potentials (EPSPs). The EPSP amplitude decreased by 75 ± 3% after 10-min, 1-Hz stimulation and by 86 ± 6% after 1-s, 100-Hz stimulation. Moreover, partial pharmacological blockade of ionotropic glutamate receptors was sufficient to suppress epileptiform discharges and enhance the antiepileptic effects of stimulation. In conclusion, this study showed that both low- and high-frequency electrical stimulation possessed antiepileptic effects in the neocortex in vitro, established the parameters determining the antiepileptic efficacy of both stimulation paradigms, and suggested that the antiepileptic effects of stimulation were mediated mostly by short-term synaptic depression of excitatory neurotransmission.

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