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Conversations with a Neuron, Volume 4

The Impact of Optogenetics on Neurodegenerative Diseases

A new study shows that astrocytes expressing Opto-α1AR may potentially be able to normalize neurons communicating with a target cell across a synapse in neurodegenerative diseases like Alzheimer’s.

Author: Aisha El-Hoot

Neurophysiology

This study used optogenetics to investigate modulates of neuronal activity. Optogenetics uses light to target and stimulates astrocytes’ activity with high spatial and temporal resolution.1 The results of this study are essential further to normalize synaptic transmission and plasticity defects in neurodegenerative disorders.

In an article published by Molecular Sciences, Evgenii Gerasimov, the study describes the use of two different opsins a group of proteins (Opto-α1AR and ChR2) expressed in astrocytes to determine the improvement of neuronal activity by 5 seconds of continuous light stimulation.2 Astrocytes play an important role in maintaining and regulating neural networks in the brain. Astrocytes regulate neuronal activity through extracellular concentration of potassium ions.2 This study looks at astrocytes in the hippocampal pyramidal neuron region of the brain. Optogenetics has been used to manipulate the activity of many different neurons.3 The method of using optogenetics has been becoming more and more common because it is a way to manage the activity of a specific neuron.   

In this study, four mice expressed ChR2, and three mice expressed Opto-α1AR. Mice were injected with either ChR2 or Opto-α1AR into the hippocampal area of the brain and after three weeks, an immunohistochemical was performed. Immunohistochemical is where the mice are put down, and slices of their brain are obtained and stained with a dye to label and identify the expression we are looking for. By spontaneous synaptic currents, the increased number of responses was by astrocytes expressing ChR2 and activated by 5 seconds of stimulation of the LED light.2 As for activation of Opto-α1AR showed an increase of excited firing in hippocampal neurons.2

Overall, the data indicated that the use of Opto-α1AR opsin expressed in astrocytes regulating neuronal functioning could later be used to correct neuronal network dysfunction and enhance synaptic plasticity in neurodegenerative diseases.2 Stimulation of astroglia that changes to reactive glia can cause the death of neurons as well as add to neuroinflammation.3 

Drawing of a mouse with a clear body so that the brain is visable. Optognetic light shining on brain and dish
Figure 1. Using optogenetics to detect ChR2 and Opto-α1AR from the hippocampal region of mice brain through immunochemistry.

The results of this study supported that using optogenetics to activate astrocytes can lead to the improvement of neuronal activity. Improvement in long-term synaptic plasticity in on one of the proteins expressed through stimulation in hippocampal astrocytes.2 Further studies that can be done are mouse models that have neurodegenerative diseases need to evaluate the accuracy of stimulation with brain slices in order to avoid any kinds of negative astrocyte stimulation on brain function.2

 

[+] References

1.

Deisseroth K. Optogenetics. Nat Methods. 2011;8(1):26-29. doi:10.1038/nmeth.f.324 

 

2.

Gerasimov, E., Erofeev, A., Borodinova, A., Bolshakova, A., Balaban, P., Bezprozvanny, I., & Vlasova, O. L. (2021). Optogenetic Activation of Astrocytes-Effects on Neuronal Network Function. International journal of molecular sciences22(17), 9613. https://doi.org/10.3390/ijms22179613

 

3.

Mahmoudi P, Veladi H, Pakdel FG. Optogenetics, Tools and Applications in Neurobiology. J Med Signals Sens. 2017;7(2):71-79. 

[+] Other Work By Aisha El-Hoot

The Impact That Language Exposure has on Children’s Brains

Neuroanatomy

This study evaluates the relationship of children’s language experience to the development of white matter microstructural relationship with conversational turns.

Detecting Alzheimer’s Disease through Ocular Imagining

Neuroscience In Review