Electric field effects on neuronal input–output relationship by regulating NMDA spikes

Fan, Yaqin; Wei, Xile; Lu, Meili; Wang, Jiang; Yi, Guosheng

doi:10.1007/s11571-022-09922-y

Cited by 3 publications

(4 citation statements)

References 39 publications

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“…Thes results are consistent with the modulation effect of EF on pyramidal neuron. [24,25] Also, we identify the effects of dendritic morphology (dendritic length and branches), synaptic distributions (cluster and scatter) on EF-regulated dendritic integration. Our results show that the modulation influence of EF on global dendritic integration is more prominent than on local dendritic integration.…”

Section: Discussionmentioning

confidence: 99%

“…To identify the influence of EFregulated dendritic integration on AP generation, we apply a current clamp to soma to reproduce the EF-induced somatic polarization. [24,25] The difference between EF stimulation and current clamp stimulation is the little dendritic polarization in the case of current clamp stimulation. Therefore, the respective contribution of EF-regulated dendritic integration and EFinduced somatic polarization to AP generation can be identified by comparing the synaptic threshold under the EF stimulation with that under the current clamp stimulation.…”

Section: Synaptic Activation and Analysis Of Input-output Relationshipmentioning

confidence: 99%

“…As described in the article of Augusto and Gambino, [23] the threshold and duration in time of NMDA spike depend on the baseline membrane potential, which suggests the modulatory influence of EF-induced polarization on the NMDA spike. Especially, our previous studies showed that the dendritic polarization of pyramidal neurons can regulate the dendritic integration of AMPA and NMDA synaptic inputs, [24,25] which further contributes to the generation of action potentials. Similarly, the EF-induced polarization at distal dendrites of interneuron can also contribute to the interneuron response by influencing the dendritic integration of NMDA synapses.…”

Section: Introductionmentioning

confidence: 99%

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Effect of applied electric fields on supralinear dendritic integration of interneuron

Fan 樊,

Wei 魏,

Lu 卢

et al. 2024

Chinese Phys. B

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Evidences show that electric fields (EFs) induced by the magnetic stimulation could modulates brain activities by regulating the excitability of GABAergic interneuron. However, it is still unclear how and why the EF-induced polarization affects the interneuron response as the interneuron receives NMDA synaptic inputs. Considering the key role of NMDA receptor-mediated supralinear dendritic integration in neuronal computations, we supposed that the applied EFs could functionally modulate interneurons’ response via regulating dendritic integration. At first, we built a simplified multi-dendritic circuit model with inhomogeneous extracellular potentials, which characterized the relationship among EF-induced spatial polarizations, dendritic integration and somatic output. By performing model-based singular perturbation analysis, we found that the equilibrium point of fast subsystem can be used to asymptotically depict the subthreshold input-output (sI/O) relationship of dendritic integration. It predicted that EF-induced strong depolarizations on the distal dendrites reduce the dendritic saturation output by reducing driving force of synaptic input, and it shifts the steep change of sI/O curve left by decreasing stimulation threshold of triggering NMDA spike. Also, the EF modulation prefers the global dendritic integration with asymmetric scatter distribution of NMDA synapses. Furthermore, we identified the respective contribution of EF-regulated dendritic integration and EF-induced somatic polarization to an action potential generation and found that they have an antagonistic effect on AP generation due to the varied NMDA spike threshold under EF stimulation.

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Section: Discussionmentioning

confidence: 99%

Section: Synaptic Activation and Analysis Of Input-output Relationshipmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of applied electric fields on supralinear dendritic integration of interneuron

Fan 樊,

Wei 魏,

Lu 卢

et al. 2024

Chinese Phys. B

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“…Decades of experimental and modeling studies have shown that the EF-induced polarization affects the spatial heterogeneity of membrane potential, which contributes to the variation of stimulation threshold for triggering action potential, spike timing and synaptic plasticity 17,18 . Especially, our previous studies pointed out that the EF-induced dendritic polarization plays an important role in the neuronal input-output relationship by affecting dendritic activities [19][20][21][22] . Therefore, the change of dendritic transmembrane potential caused by EFs seems to regulate the input-output function of TRN neuron via modulating IT -dependent dCa response.…”

Section: Introductionmentioning

confidence: 99%

State-dependent Modulation of Low-threshold-current-regulated Dendritic Ca 2+ Response in Thalamic Reticular Neurons with Extracellular Electric Fields

Fan

Wei

et al. 2023

Preprint

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Deep brain stimulation (DBS) in thalamic reticular nucleus (TRN) neuron provides a novel treatment for drug-resistant epilepsy via the induced electrical field (EFs). However, the mechanisms underlying EF effects remain unclear. This paper investigated how EFs regulate low-threshold dendritic Ca2+ (dCa) response and thus contribute to the input-output relationship of TRN cell. Our results showed that EFs modulate firing modes differently in a neuronal state-dependent manner. At the depolarized state, EFs only regulate the spike timing of a somatic stimulus-evoked single action potential (AP) with less contribution in the regulation of dCa response but could induce the transition between a dendritic stimulus-evoked single AP and a tonic burst of APs via the moderate regulation of dCa response. At the hyperpolarized state, EFs have significant effects on the dCa response, which modulate the large dCa response-dependent burst discharge and even cause a transition from this type of burst discharge to a single AP with less dCa response. Moreover, EF effects on stimulation threshold of somatic spiking prominently depend on EF-regulated dCa responses and the onset time differences between the stimulus and EF give rise to the distinct effect in the EF regulation of dCa responses. Finally, the larger neuronal axial resistance tends to result in the dendritic stimulus-evoked dCa response independent of somatic state. Interestingly, in this case, the EF application could reproduce the similar somatic state-dependent dCa response to dendritic stimulus which occurs in the case of lower axial resistance. These results suggest that the influence of EF on neuronal activities depends on neuronal intrinsic properties, which provides insight into understanding how DBS in TRN neuron modulates epilepsy from the point of view of biophysics.

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State-dependent modulation of low-threshold-current-regulated dendritic Ca2+ response in thalamic reticular neurons with extracellular electric fields

Fan,

Wei,

et al. 2023

Sci Rep

Self Cite

View full text Add to dashboard Cite

Deep brain stimulation (DBS) in thalamic reticular nucleus (TRN) neuron provides a novel treatment for drug-resistant epilepsy via the induced electrical field (EFs). However, the mechanisms underlying EF effects remain unclear. This paper investigated how EFs regulate low-threshold dendritic Ca2+ (dCa) response and thus contribute to the input–output relationship of TRN cell. Our results showed that EFs modulate firing modes differently in a neuronal state-dependent manner. At the depolarized state, EFs only regulate the spike timing of a somatic stimulus-evoked single action potential (AP) with less contribution in the regulation of dCa response but could induce the transition between a dendritic stimulus-evoked single AP and a tonic burst of APs via the moderate regulation of dCa response. At the hyperpolarized state, EFs have significant effects on the dCa response, which modulate the large dCa response-dependent burst discharge and even cause a transition from this type of burst discharge to a single AP with less dCa response. Moreover, EF effects on stimulation threshold of somatic spiking prominently depend on EF-regulated dCa responses and the onset time differences between the stimulus and EF give rise to the distinct effect in the EF regulation of dCa responses. Finally, the larger neuronal axial resistance tends to result in the dendritic stimulus-evoked dCa response independent of somatic state. Interestingly, in this case, the EF application could reproduce the similar somatic state-dependent dCa response to dendritic stimulus which occurs in the case of lower axial resistance. These results suggest that the influence of EF on neuronal activities depends on neuronal intrinsic properties, which provides insight into understanding how DBS in TRN neuron modulates epilepsy from the point of view of biophysics.

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Electric field effects on neuronal input–output relationship by regulating NMDA spikes

Cited by 3 publications

References 39 publications

Effect of applied electric fields on supralinear dendritic integration of interneuron

Effect of applied electric fields on supralinear dendritic integration of interneuron

State-dependent Modulation of Low-threshold-current-regulated Dendritic Ca 2+ Response in Thalamic Reticular Neurons with Extracellular Electric Fields

State-dependent modulation of low-threshold-current-regulated dendritic Ca2+ response in thalamic reticular neurons with extracellular electric fields

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