TY - JOUR
T1 - Optoα1AR activation in astrocytes modulates basal hippocampal synaptic excitation and inhibition in a stimulation-specific manner
AU - Courtney, Connor D.
AU - Sobieski, Courtney
AU - Ramakrishnan, Charu
AU - Ingram, Robbie J.
AU - Wojnowski, Natalia M.
AU - DeFazio, R. Anthony
AU - Deisseroth, Karl
AU - Christian-Hinman, Catherine A.
N1 - This work was supported by a Whitehall Foundation Research Grant, a Brain Research Foundation Fay/Frank Seed Grant, a CURE Epilepsy Taking Flight Award (Catherine A. Christian‐Hinman), and the Beckman Institute (Courtney Sobieski and Natalia M. Wojnowski). Catherine A. Christian‐Hinman was also supported by NIH/NINDS grant R01 NS105825 and Robbie J. Ingram was supported by F31 NS124306. We thank Leanna Leverton, Lola Lozano, and Jordyn Robare for assistance with mouse colony maintenance.
PY - 2023/12
Y1 - 2023/12
N2 - Astrocytes play active roles at synapses and can monitor, respond, and adapt to local synaptic activity. While there is abundant evidence that astrocytes modulate excitatory transmission in the hippocampus, evidence for astrocytic modulation of hippocampal synaptic inhibition remains more limited. Furthermore, to better investigate roles for astrocytes in modulating synaptic transmission, more tools that can selectively activate native G protein signaling pathways in astrocytes with both spatial and temporal precision are needed. Here, we utilized AAV8-GFAP-Optoα1AR-eYFP (Optoα1AR), a viral vector that enables activation of Gq signaling in astrocytes via light-sensitive α1-adrenergic receptors. To determine if stimulating astrocytic Optoα1AR modulates hippocampal synaptic transmission, recordings were made in CA1 pyramidal cells with surrounding astrocytes expressing Optoα1AR, channelrhodopsin (ChR2), or GFP. Both high-frequency (20 Hz, 45-ms light pulses, 5 mW, 5 min) and low-frequency (0.5 Hz, 1-s pulses at increasing 1, 5, and 10 mW intensities, 90 s per intensity) blue light stimulation were tested. 20 Hz Optoα1AR stimulation increased both inhibitory and excitatory postsynaptic current (IPSC and EPSC) frequency, and the effect on miniature IPSCs (mIPSCs) was largely reversible within 20 min. However, low-frequency stimulation of Optoα1AR did not modulate either IPSCs or EPSCs, suggesting that astrocytic Gq-dependent modulation of basal synaptic transmission in the hippocampus is stimulation-dependent. By contrast, low-frequency stimulation of astrocytic ChR2 was effective in increasing both synaptic excitation and inhibition. Together, these data demonstrate that Optoα1AR activation in astrocytes changes basal GABAergic and glutamatergic transmission, but only following high-frequency stimulation, highlighting the importance of temporal dynamics when using optical tools to manipulate astrocyte function.
AB - Astrocytes play active roles at synapses and can monitor, respond, and adapt to local synaptic activity. While there is abundant evidence that astrocytes modulate excitatory transmission in the hippocampus, evidence for astrocytic modulation of hippocampal synaptic inhibition remains more limited. Furthermore, to better investigate roles for astrocytes in modulating synaptic transmission, more tools that can selectively activate native G protein signaling pathways in astrocytes with both spatial and temporal precision are needed. Here, we utilized AAV8-GFAP-Optoα1AR-eYFP (Optoα1AR), a viral vector that enables activation of Gq signaling in astrocytes via light-sensitive α1-adrenergic receptors. To determine if stimulating astrocytic Optoα1AR modulates hippocampal synaptic transmission, recordings were made in CA1 pyramidal cells with surrounding astrocytes expressing Optoα1AR, channelrhodopsin (ChR2), or GFP. Both high-frequency (20 Hz, 45-ms light pulses, 5 mW, 5 min) and low-frequency (0.5 Hz, 1-s pulses at increasing 1, 5, and 10 mW intensities, 90 s per intensity) blue light stimulation were tested. 20 Hz Optoα1AR stimulation increased both inhibitory and excitatory postsynaptic current (IPSC and EPSC) frequency, and the effect on miniature IPSCs (mIPSCs) was largely reversible within 20 min. However, low-frequency stimulation of Optoα1AR did not modulate either IPSCs or EPSCs, suggesting that astrocytic Gq-dependent modulation of basal synaptic transmission in the hippocampus is stimulation-dependent. By contrast, low-frequency stimulation of astrocytic ChR2 was effective in increasing both synaptic excitation and inhibition. Together, these data demonstrate that Optoα1AR activation in astrocytes changes basal GABAergic and glutamatergic transmission, but only following high-frequency stimulation, highlighting the importance of temporal dynamics when using optical tools to manipulate astrocyte function.
KW - GABA
KW - glia
KW - glutamate
KW - hippocampus
KW - optogenetics
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U2 - 10.1002/hipo.23580
DO - 10.1002/hipo.23580
M3 - Article
C2 - 37767862
AN - SCOPUS:85173126044
SN - 1050-9631
VL - 33
SP - 1277
EP - 1291
JO - Hippocampus
JF - Hippocampus
IS - 12
ER -