@conference{
author = "Nikolić, Ljiljana",
year = "2023",
abstract = "Communication between neurons and astrocytes and its role in information
processing in the brain has been repeatedly demonstrated over the past two decades. Evidence
for neurons communicating with astroglia is solid, but the signaling pathways leading back
from glial-to-neuronal activity are difficult to study and remain highly controversial. There is
a general agreement that intracellular Ca2+ is a key signaling pathway activated in astrocytes in
response to neuronal signals. However, it is still debated whether and how intracellular Ca2+
contributes to the release of gliotransmitters by astrocytes and to their regulation of synaptic
transmission and neuronal excitability [1, 2]. The main limitation causing these controversies
is the difficulty to activate astrocytes in a reliable and specific manner. To overcome this we
used widespread transgenic expression of light-gated cation channel channelrhodopsin-2
specifically in astrocytes. This optogenetic approach enabled us to control astrocyte activity by
the blue light and to study glia-related properties of neuronal activity regulation. Using slice
preparations we found that selective photoactivation of astrocytes reliably evoked glial Ca2+
responses, increased glutamatergic synaptic transmission in the hippocampus and increased
firing of pyramidal neurons [3]. Neuronal firing was regulated by the Ca2+-dependent glutamate
release from astrocytes and activation of neuronal extra-synaptic NMDA receptors. Optical
activation of astrocytes also increased synaptic transmission through activation of presynaptic
metabotropic glutamate receptors in case of pyramidal neurons and presynaptic NMDA
receptors in case of granule cells of the dentate gyrus [3, 4]. In this model of blue light
stimulated astrocytes, Ca2+ increase and subsequent glutamate release were amplified by
ATP/ADP-mediated autocrine activation of purinergic P2Y1 receptors on astrocytes. Using
optogenetic approach targeting astrocytes we revealed that described autocrine purinergic loop
of astroglia is also permanently active in a mouse model of temporal lobe epilepsy and that it
sustains abnormal synaptic activity [4]. Moreover, blockade of P2Y1 receptor-mediated
signaling in the dentate gyrus astrocytes restored regular glutamatergic synaptic transmission
in epilepsy, just as in the case of photoactivated astrocytes. These findings demonstrate that
optogenetic astrocyte activation is an effective approach to study glia-to-neuron
communication and to understand how it perturbs in disease.
REFERENCES
[1] N. Hamilton, D Attwell., Nat. Rev. Neurosci. 11 (2010), 227 238.
[2] N. Bazargani, Attwell, D., Nat. Neurosci. 19 (2016), 182 189.
[3] W. Shen, Lj. Nikolic et al., Sci. Rep. 7 (2017), 11280. J. Appl. Opt. A 33 (1989), 357 376.
[4] Lj.Nikolic, W. Shen et al., Glia. 66 (2018), 2673-2683.",
publisher = "Belgrade: Institute of Physics",
journal = "Book of abstracts: 16th Photonics Workshop: Conference; 2023 Mar 12-15; Kopaonik, Serbia",
title = "Application of optogenetics for studying neuronal activity via glial photostimulation",
pages = "47",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5512"
}