Optogenetic tagging

Sunday, 20 March, 2022

 Optotagging/Phototagging is a photostimulation-assisted identification of neuronal populations. Since, neural circuits are made of a vast diversity of neuronal cell types. This powerful technique allows to study neuronal networks, circuits and cellular mechanisms and to gain a comprehensive and ever more detailed understanding of the complex structure and function of the brain. So far, a great progress been made for classifying neurons based on morphological, molecular, and functional properties. However, understanding how this heterogeneity contributes to brain function during behavior is largely unexplored.

 

 Optogenetic manipulations are particularly powerful when combined with behavior. In the most common paradigm, ontogenetically targeted neurons are activated or silenced via an implanted optical fibre connected to laser or LED, while the animals participate in a task. This approach provides insights into the role of the targeted cells in the observed behavior. Importantly, this approach allows within subject and within session comparisons of manipulated and non-manipulated trials to understand the role of distinct pathways in freely behaving animals.  This technique is not intending to manipulate neuronal activity to control the behavior but rather to identify a subset of neurons and later monitor their natural activity.

 

 The cholinergic, dopaminergic and serotonergic neurons play an important role in association with learning, memory and attention. However, their neuronal activity during behavior is unknown. Our lab is interested in unravelling the activity cholinergic including the dopaminergic and serotonergic neurons and their role in better understanding the neurodegenerative diseases (e.g. Alzheimer’s and Parkinson’s disease).

 

 Therefore, combining electrophysiology with opsins target to defined subsets of neurons allow us to identify the specific cell types in vitro and in vivo (e.g. cholinergic, dopaminergic and serotonergic). Moreover, by using optotagging combined with cell-type-specific expression enables identification, quantification, and characterization of neurons. Furthermore, optotagging combined with electrophysiological recordings enables the identification of projection profiles and pathway-specific subpopulations during behavioural experiments.

Figure: Optotagging and Electrophysiology during Behavior

(A)Experimental setup (B) Recording (C) Cluster shown in red (D) Histogram showing peak of a tagged neuron (E) Tagged neuron spike

 

 

Research methods