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Updated: Jun 14, 2026

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Ex Vivo Optogenetic Interrogation of Long-Range Synaptic Transmission and Plasticity from Medial Prefrontal Cortex to Lateral Entorhinal Cortex
Published on: February 25, 2022
Optogenetic insights into short- and long-duration random noise electrical stimulation
Jorge Gutierrez1, Nikte Requejo-Mendoza2,3, Ranier Gutierrez2,3
1Institute of Physiology, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico.
Journal of Neurophysiology
|June 12, 2026
Summary
Short-duration random noise stimulation (RNS) attenuates cortical activity via neurotransmission, while long-duration RNS enhances it through excitability saturation, impacting human transcranial RNS protocols.
Area of Science:
- Neuroscience
- Neurostimulation
- Cortical Excitability
Background:
- Transcranial random noise stimulation (tRNS) duration influences cortical activity: 10 minutes enhances motor-evoked potentials, while 4 minutes attenuates task-evoked BOLD responses.
- These duration-dependent effects suggest distinct underlying cellular mechanisms that require further investigation.
Purpose of the Study:
- To investigate the distinct physiological mechanisms of long-term (10 min) versus short-term (2 min) cortical random noise stimulation (RNS).
- To determine if optogenetic manipulation of neurotransmission alters RNS effects in mice.
Main Methods:
- Utilized optogenetic transgenic mice (Thy1-ChR2-YFP and VGAT-ChR2-YFP) to evoke glutamate or GABA release with blue light.
- Administered 10-minute and 2-minute cortical RNS and assessed somatosensory evoked potentials.
- Compared RNS effects in transgenic mice with wild-type littermates and sham stimulation controls.
Main Results:
- 10-minute cortical RNS facilitated somatosensory evoked potentials similarly in transgenic and wild-type mice, suggesting a ceiling effect on cortical excitability.
- 2-minute cortical RNS-induced attenuation of evoked potentials was reversed by optogenetic stimulation in transgenic mice.
- Sham stimulation showed no significant effects.
Conclusions:
- Long-duration RNS (10 min) likely enhances cortical responses via a saturation effect, engaging maximal facilitation irrespective of specific neurotransmitter pathways.
- Short-duration RNS (2 min) attenuates responses through mechanisms dependent on the glutamate-GABA balance.
- These findings highlight duration-dependent cellular mechanisms and have implications for optimizing tRNS protocols in humans.

