A protein and cation channel first found in green algae (Chlamydomonas reinhardtii). It opens upon stimulation by blue light, and neurons expressing ChR2 fire action potentials. The isomerization of all-trans retinal allows the channel to open, resulting in an influx of Na+ that is greater than the outflow of K+.

Channelrhodopsin-2 (ChR2)

An inward Cl- pump found in archaea. Neurons expressing halorhodopsin are hyperpolarized (silenced) in response to yellow light.

Halorhodopsin

Viral vectors (ex. adeno-associated viruses, or AAV) are a common method to transfer light-sensitive opsins into the brain for experiments involving optogenetics. By packaging opsin genes fused with cell-type specific promoters into the viral vector, the opsin is expressed in cell types of interest. Promoters must be small enough to be packaged into viral vectors. In vivo, viral vectors are delivered via stereotaxic injections.

Viral vectors in optogenetics

Optogenetics can be performed in a living organism. First, a cannula (thin tube) is surgically inserted into a brain region expressing an opsin. Then, an optical fiber that can deliver light is inserted into the cannula, allowing the experimenter to compare behavior when the light is off (neurons of interest are not stimulated) and when the light is on (neurons of interest are stimulated within milliseconds). A limitation is that implanting the optical fiber may cause physical damage.

Optogenetics in vivo

ChR2-assisted circuit mapping (CRACM) is a method of brain mapping using optogenetics. By making presynaptic neurons of interest express ChR2, the experimenter can deliver light and record which postsynaptic neurons depolarize (excitatory synapse) or hyperpolarize (inhibitory synapse). CRACM is useful in mapping long-range connections but cannot be performed in vivo.

Brain mapping with optogenetics

Optogenetic stimulation has been demonstrated to induce long-term potentiation and long-term depression, both in vitro and in vivo. It can affect locomotion, motor learning and memory consolidation.

Optogenetics and plasticity

* Epilepsy
* Vision restoration 
* Parkinson's disease 
* Chronic pain

Therapeutic applications of optogenetics

Rodents are the most widely used model organism in neuroscience and biomedical research. Rats and mice differ significantly in gene expression, social behaviors, and physiology, giving them unique advantages and disadvantages as the favorable model in any particular research. For example, mice were more commonly used due to their larger “genetic toolbox,” which includes transgenic and “knockout”/”knock-in” mice. However, adult rats typically weigh up to ten times more than adult mice. Their larger size makes surgery and other invasive procedures such as catheter insertion easier to perform, while mice are chosen for optogenetics experiments because light passes more easily through their smaller brains and can therefore reach deeper regions of the brain.

Rodentia (mouse, rat)

A genetic approach to control the activity of specific neurons by light. Optogenetics generally makes use of the selective expression of opsins, proteins that respond to certain types of light.

University of Michigan - Ann Arbor

- Electroencephalogram (EEG)
- Golgi stain
- Nissl stain
- Optogenetics
- Functional magnetic resonance imaging (fMRI)

Methods of Brain Mapping

Luo, L. (2020). Principles of Neurobiology (2nd ed.). CRC Press. 

Principles of Neurobiology, 2nd edition (2020)

A neural stain that shows the cell bodies in a particular region. This works by targeting RNA in cell bodies. These are good for measuring cell density and the size of cell bodies. 

Nissl Stain

These types of stains show neurons in detail, revealing dendrites and axons. These are good for showing types and shapes of different neurons. 

Golgi Stain

A documentation of spontaneous gross electrical activity of the brain recorded by placing electrodes on the scalp. The measured electrical activity is not prompted by particular stimuli, and may also be referred to as "brain waves."  

Electroencephalogram (EEG) 

Functional magnetic resonance imaging (fMRI) is an effective tool for analyzing brain functionality. It is capable of tracking the functional response of the brain through Blood Oxygen Level Dependent (BOLD) contrast. Increased neuronal activity leads to local increase in energy and oxygen consumption. Essentially, the BOLD effect is a contrast caused by the relative decrease in the magnetic field irregularities due to relative increase in the oxyHb level contributed by the blood flowing in the brain region with increased activity.

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