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A light-gated potassium channel for sustained neuronal inhibition.

Alberio, Laura and Locarno, Andrea and Saponaro, Andrea and Romano, Edoardo and Bercier, Valérie and Albadri, Shahad and Simeoni, Frederica and Moleri, Silvia and Pelucchi, Silvia and Porro, Alessandro and Marcello, Elena and Barsotti, Noemi and Kukovetz, Kerri and Boender, Arjen J. and Contestabile, Andrea and Luo, Shizhen and Moutal, Aubin and Ji, Yingshi and Romani, Giulia and Beltrame, Monica and Del Bene, Filippo and Di Luca, Monica and Khanna, Rajesh and Colecraft, Henry M. and Pasqualetti, Massimo and Thiel, Gerhard and Tonini, Raffaella and Moroni, Anna :
A light-gated potassium channel for sustained neuronal inhibition.
In: Nature methods, 15 (11) pp. 969-976. ISSN 1548-7105
[Article] , (2018)

Abstract

Currently available inhibitory optogenetic tools provide short and transient silencing of neurons, but they cannot provide long-lasting inhibition because of the requirement for high light intensities. Here we present an optimized blue-light-sensitive synthetic potassium channel, BLINK2, which showed good expression in neurons in three species. The channel is activated by illumination with low doses of blue light, and in our experiments it remained active over (tens of) minutes in the dark after the illumination was stopped. This activation caused long periods of inhibition of neuronal firing in ex vivo recordings of mouse neurons and impaired motor neuron response in zebrafish in vivo. As a proof-of-concept application, we demonstrated that in a freely moving rat model of neuropathic pain, the activation of a small number of BLINK2 channels caused a long-lasting (>30 min) reduction in pain sensation.

Item Type: Article
Erschienen: 2018
Creators: Alberio, Laura and Locarno, Andrea and Saponaro, Andrea and Romano, Edoardo and Bercier, Valérie and Albadri, Shahad and Simeoni, Frederica and Moleri, Silvia and Pelucchi, Silvia and Porro, Alessandro and Marcello, Elena and Barsotti, Noemi and Kukovetz, Kerri and Boender, Arjen J. and Contestabile, Andrea and Luo, Shizhen and Moutal, Aubin and Ji, Yingshi and Romani, Giulia and Beltrame, Monica and Del Bene, Filippo and Di Luca, Monica and Khanna, Rajesh and Colecraft, Henry M. and Pasqualetti, Massimo and Thiel, Gerhard and Tonini, Raffaella and Moroni, Anna
Title: A light-gated potassium channel for sustained neuronal inhibition.
Language: English
Abstract:

Currently available inhibitory optogenetic tools provide short and transient silencing of neurons, but they cannot provide long-lasting inhibition because of the requirement for high light intensities. Here we present an optimized blue-light-sensitive synthetic potassium channel, BLINK2, which showed good expression in neurons in three species. The channel is activated by illumination with low doses of blue light, and in our experiments it remained active over (tens of) minutes in the dark after the illumination was stopped. This activation caused long periods of inhibition of neuronal firing in ex vivo recordings of mouse neurons and impaired motor neuron response in zebrafish in vivo. As a proof-of-concept application, we demonstrated that in a freely moving rat model of neuropathic pain, the activation of a small number of BLINK2 channels caused a long-lasting (>30 min) reduction in pain sensation.

Journal or Publication Title: Nature methods
Volume: 15
Number: 11
Divisions: 10 Department of Biology
10 Department of Biology > Plant Membrane Biophysics
Date Deposited: 05 Nov 2018 12:55
Identification Number: pmid:30377377
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