Role of cortical cell type and morphology in subthreshold and suprathreshold uniform electric field stimulation in vitro.

Brain stimulation · 2009 · Mixed · Low evidence

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MixedLow evidencePaper 3351

Study snapshot

PublicationBrain stimulation · 2009

Study typein_vitro

Reported directionMixed

Evidence ratingLow

Abstract

BACKGROUND: The neocortex is the most common target of subdural electrotherapy and noninvasive brain stimulation modalities, including transcranial magnetic stimulation (TMS) and transcranial current simulation (TCS). Specific neuronal elements targeted by cortical stimulation are considered to underlie therapeutic effects, but the exact cell type(s) affected by these methods remains poorly understood. OBJECTIVE: We determined whether neuronal morphology or cell type predicted responses to subthreshold and suprathreshold uniform electric fields. METHODS: We characterized the effects of subthreshold and suprathreshold electrical stimulation on identified cortical neurons in vitro. Uniform electric fields were applied to rat motor cortex brain slices, while recording from interneurons and pyramidal cells across cortical layers, using a whole-cell patch clamp. Neuron morphology was reconstructed after intracellular dialysis of biocytin. Based solely on volume-weighted morphology, we developed a parsimonious model of neuronal soma polarization by subthreshold electric fields. RESULTS: We found that neuronal morphology correlated with somatic subthreshold polarization. Based on neuronal morphology, we predict layer V pyramidal neuronal soma to be individually the most sensitive to polarization by optimally oriented subthreshold fields. Suprathreshold electric field action potential threshold was shown to reflect both direct cell polarization and synaptic (network) activation. Layer V/VI neuron absolute electric field action potential thresholds were lower than layer II/III pyramidal neurons and interneurons. Compared with somatic current injection, electric fields promoted burst firing and modulated action potential firing times. CONCLUSIONS: We present experimental data indicating that cortical neuron morphology relative to electric fields and cortical cell type are factors in determining sensitivity to sub- and supra-threshold brain stimulation.

Machine Enhanced Logic

AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typein_vitro

Effect directionmixed

PopulationRat motor cortex brain slices (in vitro); recorded cortical interneurons and pyramidal cells across layers

Sample sizeNot supplied

ExposureNot supplied

Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

In rat motor cortex slices, neuronal morphology correlated with somatic subthreshold polarization in uniform electric fields; a morphology-based model predicted layer V pyramidal neuron somas to be most sensitive when fields are optimally oriented. Suprathreshold action potential thresholds reflected both direct polarization and synaptic/network activation, with layer V/VI neurons showing lower absolute field thresholds than layer II/III pyramidal neurons and interneurons. Compared with somatic current injection, electric fields promoted burst firing and modulated spike timing.

Outcomes measured

Somatic subthreshold polarization
Action potential threshold under suprathreshold electric fields
Burst firing and action potential timing modulation
Relationship of neuronal morphology/cell type to electric-field sensitivity

Limitations

In vitro brain-slice preparation; findings may not generalize to in vivo stimulation
No sample size reported in abstract
Electric field parameters (e.g., intensity, waveform, duration) not specified in abstract

View raw extracted JSON

{
  "study_type": "in_vitro",
  "exposure": {
    "band": null,
    "source": "uniform electric field stimulation (brain slice)",
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": null
  },
  "population": "Rat motor cortex brain slices (in vitro); recorded cortical interneurons and pyramidal cells across layers",
  "sample_size": null,
  "outcomes": [
    "Somatic subthreshold polarization",
    "Action potential threshold under suprathreshold electric fields",
    "Burst firing and action potential timing modulation",
    "Relationship of neuronal morphology/cell type to electric-field sensitivity"
  ],
  "main_findings": "In rat motor cortex slices, neuronal morphology correlated with somatic subthreshold polarization in uniform electric fields; a morphology-based model predicted layer V pyramidal neuron somas to be most sensitive when fields are optimally oriented. Suprathreshold action potential thresholds reflected both direct polarization and synaptic/network activation, with layer V/VI neurons showing lower absolute field thresholds than layer II/III pyramidal neurons and interneurons. Compared with somatic current injection, electric fields promoted burst firing and modulated spike timing.",
  "effect_direction": "mixed",
  "limitations": [
    "In vitro brain-slice preparation; findings may not generalize to in vivo stimulation",
    "No sample size reported in abstract",
    "Electric field parameters (e.g., intensity, waveform, duration) not specified in abstract"
  ],
  "evidence_strength": "low",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "cortex",
    "uniform electric field",
    "transcranial current stimulation",
    "TCS",
    "TMS",
    "brain stimulation",
    "patch clamp",
    "pyramidal neurons",
    "interneurons",
    "neuronal morphology",
    "subthreshold polarization",
    "action potential threshold",
    "burst firing"
  ],
  "suggested_hubs": [
    {
      "slug": "tms-tcs-mechanisms",
      "weight": 0.78,
      "reason": "Study examines cellular/morphological determinants of responses to electric fields relevant to transcranial current stimulation and cortical stimulation mechanisms."
    }
  ]
}

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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1016/j.brs.2009.03.007
PubMed: 20161507

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