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Integration of Neuronal Activity Monitoring with Optogenetics

The intricate structure of the human brain, with millions of interconnected neurons working in synergy, is the foundation for our cognition, behavior, and consciousness. Neurobiologists have always sought for effective tools to delve deep into this complex neuronal network. Enter optogenetics, a groundbreaking technology that uses light to control neurons allowing us to understand brain functions at a cellular level. Equally transformative is the parallel development of neuronal activity monitoring technologies which allow direct observation of neuronal communication. By integrating these two powerful tools, scientists can modulate and monitor neuronal activity, thus unfolding the mysteries of the brain.

Creative Biolabs integrates neuronal activity monitoring and optogenetic technologies to provide our clients with a comprehensive range of quality research services and research tools.

Services What We Do Advantages
Neuronal Activity Monitor Services Neuronal activity monitoring service is one of the proven services provided by our platform. We are able to provide novel tools for imaging and recording neuronal activity in animals to capture neural activity.
  • Novel tool development
  • The most realistic readings
  • Real-time imaging
Optogenetic Actuators We offer the search for novel Optogenetic Actuators and genetic alterations to existing actuators, which enable precise optical control of single-cell activity with high temporal resolution.
  • Highly specialized staff
  • Advanced platforms
  • Comprehensive support and tools
Optogenetic Indicators We provide optogenetic tools, including a variety of optogenetic indicators that can be easily delivered to target neuronal populations, using a variety of genetic approaches to achieve cell type-specific manipulation.
  • Does not affect other cells
  • Compatibility with genetics
  • Wide range of applications

The Emergence of Optogenetics

Traditionally, neuroscientists used electrical stimulation to probe neuronal networks. While effective in activating neurons, electrical stimulation lacked precision, often influencing nearby neurons and other cell types leading to ambiguous results. The development of optogenetics revolutionized this field, allowing precise targeting and control of individual neurons.

Optogenetics – a combination of optics and genetics – involves using light of specific wavelengths to control genetically modified neurons. This modification often involves introducing genes that code for light-sensitive proteins, called opsins, into neurons' DNA. Upon exposure to light, these opsins change shape to allow ions to flow through the neuron's membrane, triggering an action potential.

Currently, two major families of opsins are employed in optogenetic studies:

  • Channelrhodopsins (i.e., ChR2) that depolarize neurons
  • Inhibitory opsins (i.e., halorhodopsins and archaerhodopsins) that hyperpolarize neurons
  • Additional opsin variations have been developed to cater to various experimental requirements, such as higher light sensitivity, color tuning, and bipolar control (activation and inhibition).

Integration of Neuronal Activity Monitoring and Optogenetics

Complementing optogenetic control methods, a wide array of neuronal activity monitoring techniques has been developed. This includes invasive techniques, like patch clamp electrophysiology and multi-electrode array recording, and noninvasive techniques, like functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS). These techniques have been bolstered by the advent of genetically encoded voltage indicators (GEVIs), such as ArcLight and ASAPs, that provide real-time reporting of neuronal activity.

The combined use of optogenetics to control neuronal activity, with simultaneous monitoring of neuronal activity changes, provides a highly detailed picture of neuronal communication.

  • One common strategy involves using calcium indicators in conjunction with optogenetic actuators. For example, researchers can express a calcium indicator in specific neurons to monitor their activity. Simultaneously, they can use optogenetics to activate or inhibit these neurons in response to the observed activity patterns. This closed-loop system enables a more precise and targeted investigation of the causal relationships between neuronal activity and behavior.

Synergistic ensemble of optogenetic actuators and dynamic calcium indicators. Fig. 1 Synergistic ensemble of optogenetic actuators and dynamic calcium indicators.1

Applications in Neuroscience Research

It allows neuroscientists to map complex neuronal networks within the brain and to study the relationship between different regions in the brain. It can also help identify potential therapeutic targets for neurodegenerative diseases, like Alzheimer's disease and Parkinson's disease, and neuropsychiatric disorders, like depression and epilepsy.

Applications Descriptions
Circuit Mapping Combined techniques allow researchers to map neural circuits with unprecedented detail. By monitoring the activity of interconnected neurons and selectively manipulating them using optogenetics, scientists can decipher the intricate web of connections that underlie various brain functions.
Memory and Learning The real-time modulation of neuronal activity has shed light on the mechanisms underlying memory formation and learning. Researchers can now explore how specific neural circuits contribute to the encoding and retrieval of memories, paving the way for targeted interventions in conditions involving memory deficits.
CNS Disease Models The integration of these technologies has facilitated the development of more accurate disease models. Researchers can study the neural circuitry associated with various neurological disorders, such as Parkinson's disease, epilepsy, and depression, offering insights into potential therapeutic targets.

Recent developments in all-optical electrophysiology, which integrate light-based control, and readout of neuronal activity, underscore the potential of this duo. Here, optogenetics is used to stimulate neuronal activity, and the resultant voltage changes are monitored using GEVIs.

The combination of neuronal activity monitoring and optogenetics marks a major leap forward in our quest to unravel the mysteries of the brain. This powerful combination provides researchers with the tools to not only observe but actively manipulate neuronal activity, opening up new possibilities for understanding and treating neurological disorders.

As technology continues to advance, Creative Biolabs offers customized services for developing more sophisticated optogenetic tools, increasing the precision of targeting specific neuronal populations, and integrating other monitoring modalities.

Reference

  1. Kim, et al. "Synergistic ensemble of optogenetic actuators and dynamic indicators in cell biology." Molecules and Cells 41.9 (2018): 809.

For Research Use Only. Not For Clinical Use.