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Optogenetically-Induced Population Discharge Threshold as a Sensitive Measure of Network Excitability.

D C Klorig1,2, G E Alberto3,2, T Smith3

  • 1Department of Neurobiology and Anatomy dklorig@wakehealth.edu neuroptics@gmail.com.

Eneuro
|October 18, 2019
PubMed
Summary

Researchers developed a novel optogenetic method to quantify network excitability in mice. This technique precisely measures seizure susceptibility by analyzing optogenetically-induced population discharges (PDs).

Keywords:
epilepsyexcitabilityintensity responsenetworkoptogeneticsseizure

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Area of Science:

  • Neuroscience
  • Epilepsy research
  • Optogenetics

Background:

  • Network excitability, influenced by synaptic efficacy, intrinsic properties, and circuitry, dictates brain function and seizure susceptibility.
  • Understanding network excitability is crucial for deciphering circuit dynamics and developing epilepsy treatments.

Purpose of the Study:

  • To develop a sensitive, quantitative method for estimating network excitability in freely behaving mice.
  • To establish a novel optogenetic intensity-response procedure to assess seizure susceptibility.

Main Methods:

  • Utilized a novel optogenetic intensity-response procedure in freely behaving mice.
  • Synchronously activated deep sublayer CA1 pyramidal cells and varied light intensity to generate optogenetically-mediated currents.
  • Generated intensity-response curves plotting the probability of population discharges (PDs) against light intensity.

Main Results:

  • Optogenetically-induced PDs were nearly indistinguishable from spontaneous interictal spikes.
  • The chemoconvulsant pentylenetetrazol (PTZ) induced a leftward shift in the intensity-response curve, indicating increased excitability.
  • The anti-epileptic drug levetiracetam (LEV) reversed the PTZ-induced shift, demonstrating decreased excitability.
  • Optogenetically-induced PD threshold (oPDT) baselines remained stable over time.

Conclusions:

  • The novel optogenetic intensity-response procedure provides a sensitive and quantitative measure of network excitability.
  • This method is suitable for within-subject experimental designs involving pharmacological manipulations in epilepsy research.
  • The technique allows for precise assessment of pro- and anti-epileptic drug effects on network excitability.