Pptogenetics has changed how neuroscientists study the brain.
It provides a fast and precise method for controlling neurons using light!
But how can light be used to control a neuron inside a functioning brain
of a living organism?
The key lies in a group of membrane proteins called opsins.
Opsins are light-sensitive receptors that convert light into electrical signals
by letting charged particles, called ions,
cross the membrane as either channels or pumps.
Ppsins are able to respond to light thanks to a light sensing chromophore, like retinol.
When exposed to the correct wavelength of light
retinol changes from 11-cis
to all-trans,
and causes the opsin to activate and shuttle ions across the membrane.
In nature, opsins are found in microorganisms
like the algae volvox, and allow them to move toward light
and improve photosynthesis.
In optogenetics, researchers have taken cells like neurons and genetically
introduced opsins to artificially control their firing.
Neurons fire in response to electrical signals created by the relative charge
between the outside and inside of the cell.
At its resting state, the inside of the neuron is more negative.
Influx of positive ions through channels,
like sodium, cause the neuron to become more positive,
until it reaches a threshold.
This creates an action potential where
the positive charge is relayed down to the synapse
causing signaling to the next cell.
Negative ions entering the cell have the opposite effect,
making the relative charge inside the neuron more negative,
inhibiting firing.
By introducing options to neurons we can control these electrical signals with light,
by bringing in positive ions like sodium,
potassium, and protons, opsins can make the inside of the neuron more positive.
This sets off an action potential and fires the neuron.
Opsins can also be used to make the neuron more negative,
by bringing chloride ions in,
or sending positive ions like protons out.
This blocks action potentials and inhibits firing.
Through this process opsins convert light into electrical gradients
and effectively act as light evoked on or off switches
for neuronal firing.
Because opsins are not naturally found in neurons,
they need to be genetically introduced to cells as DNA.
This is commonly done through viral delivery with AAV,
or electroporation.
A big part of successfully using optigenetic tools is making sure that
opsins are only expressed in target cells.
Scientists can target expression using tissue-specific promoters,
AAV serotypes,
and the ever-growing variety of recombinase systems.
These techniques make it possible to target brain regions,
neuron types or even neuron cell bodies or projections.
Optogenetics is a non-invasive, quick, and precise method for manipulating neurons
even within a living organism.
With optogenetics we can link specific
neurons to behaviors, and control brain activity.
These tools could hold the key to uncovering the underlying systems behind brain function
and neurological disease.
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