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An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons.
J Neurosci 2016; 36(22):5961-73JN

Abstract

To investigate excitatory and inhibitory GABA actions in cortical neuronal networks, we present a novel optogenetic approach using a mouse knock-in line with conditional expression of channelrhodopsin-2 (ChR2) in GABAergic interneurons. During whole-cell recordings from hippocampal and neocortical slices from postnatal day (P) 2-P15 mice, photostimulation caused depolarization and excitation of interneurons and evoked barrages of postsynaptic GABAergic currents. Excitatory/inhibitory GABA actions on pyramidal cells were assessed by monitoring the alteration in the frequency of EPSCs during photostimulation of interneurons. We found that in slices from P2-P8 mice, photostimulation evoked an increase in EPSC frequency, whereas in P9-P15 mice the response switched to a reduction in EPSC frequency, indicating a developmental excitatory-to-inhibitory switch in GABA actions on glutamatergic neurons. Using a similar approach in urethane-anesthetized animals in vivo, we found that photostimulation of interneurons reduces EPSC frequency at ages P3-P9. Thus, expression of ChR2 in GABAergic interneurons of mice enables selective photostimulation of interneurons during the early postnatal period, and these mice display a developmental excitatory-to-inhibitory switch in GABA action in cortical slices in vitro, but so far show mainly inhibitory GABA actions on spontaneous EPSCs in the immature hippocampus and neocortex in vivo

SIGNIFICANCE STATEMENT

We report a novel optogenetic approach for investigating excitatory and inhibitory GABA actions in mice with conditional expression of channelrhodopsin-2 in GABAergic interneurons. This approach shows a developmental excitatory-to-inhibitory switch in the actions of GABA on glutamatergic neurons in neocortical and hippocampal slices from neonatal mouse pups in vitro, but also reveals inhibitory GABA actions in the neonatal mouse neocortex and hippocampus in vivo.

Authors+Show Affiliations

Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale U-901, 13273 Marseille, France, Aix-Marseille University, 13273 Marseille, France, and Laboratory of Neurobiology, Kazan Federal University, 420008 Kazan, Russia roustem.khazipov@inserm.fr guzelvaleyeva@yahoo.com.Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale U-901, 13273 Marseille, France, Aix-Marseille University, 13273 Marseille, France, and.Laboratory of Neurobiology, Kazan Federal University, 420008 Kazan, Russia.Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale U-901, 13273 Marseille, France, Aix-Marseille University, 13273 Marseille, France, and.Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale U-901, 13273 Marseille, France, Aix-Marseille University, 13273 Marseille, France, and Laboratory of Neurobiology, Kazan Federal University, 420008 Kazan, Russia roustem.khazipov@inserm.fr guzelvaleyeva@yahoo.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27251618

Citation

Valeeva, Guzel, et al. "An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 36, no. 22, 2016, pp. 5961-73.
Valeeva G, Tressard T, Mukhtarov M, et al. An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons. J Neurosci. 2016;36(22):5961-73.
Valeeva, G., Tressard, T., Mukhtarov, M., Baude, A., & Khazipov, R. (2016). An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 36(22), pp. 5961-73. doi:10.1523/JNEUROSCI.3482-15.2016.
Valeeva G, et al. An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons. J Neurosci. 2016 06 1;36(22):5961-73. PubMed PMID: 27251618.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons. AU - Valeeva,Guzel, AU - Tressard,Thomas, AU - Mukhtarov,Marat, AU - Baude,Agnes, AU - Khazipov,Rustem, PY - 2015/09/17/received PY - 2016/04/12/accepted PY - 2016/6/3/entrez PY - 2016/6/3/pubmed PY - 2017/7/7/medline KW - ChR2 KW - GABA KW - cortex KW - hippocampus KW - inhibition KW - interneurons KW - optogenetics KW - patch clamp SP - 5961 EP - 73 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 36 IS - 22 N2 - UNLABELLED: To investigate excitatory and inhibitory GABA actions in cortical neuronal networks, we present a novel optogenetic approach using a mouse knock-in line with conditional expression of channelrhodopsin-2 (ChR2) in GABAergic interneurons. During whole-cell recordings from hippocampal and neocortical slices from postnatal day (P) 2-P15 mice, photostimulation caused depolarization and excitation of interneurons and evoked barrages of postsynaptic GABAergic currents. Excitatory/inhibitory GABA actions on pyramidal cells were assessed by monitoring the alteration in the frequency of EPSCs during photostimulation of interneurons. We found that in slices from P2-P8 mice, photostimulation evoked an increase in EPSC frequency, whereas in P9-P15 mice the response switched to a reduction in EPSC frequency, indicating a developmental excitatory-to-inhibitory switch in GABA actions on glutamatergic neurons. Using a similar approach in urethane-anesthetized animals in vivo, we found that photostimulation of interneurons reduces EPSC frequency at ages P3-P9. Thus, expression of ChR2 in GABAergic interneurons of mice enables selective photostimulation of interneurons during the early postnatal period, and these mice display a developmental excitatory-to-inhibitory switch in GABA action in cortical slices in vitro, but so far show mainly inhibitory GABA actions on spontaneous EPSCs in the immature hippocampus and neocortex in vivo SIGNIFICANCE STATEMENT: We report a novel optogenetic approach for investigating excitatory and inhibitory GABA actions in mice with conditional expression of channelrhodopsin-2 in GABAergic interneurons. This approach shows a developmental excitatory-to-inhibitory switch in the actions of GABA on glutamatergic neurons in neocortical and hippocampal slices from neonatal mouse pups in vitro, but also reveals inhibitory GABA actions in the neonatal mouse neocortex and hippocampus in vivo. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/27251618/An_Optogenetic_Approach_for_Investigation_of_Excitatory_and_Inhibitory_Network_GABA_Actions_in_Mice_Expressing_Channelrhodopsin_2_in_GABAergic_Neurons_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=27251618 DB - PRIME DP - Unbound Medicine ER -