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Hebbs Rule Shown Directly In Mice With Optogenetic Tool

by on June 15, 2014

Researchers from UCSD have for the first time directly created and destroyed neural connections that connect high level sensory input and high level behavioral responses.

When we experience events that are connected, for example nausea after riding in a boat in choppy waters, we sometimes gain a “associated” or “conditioned” response that’s not causal.  In this example, merely seeing the boat incurs feelings of nausea, whether or not we ride the boat.

The seed of a simple idea presented here has given rise to a rich body of theoretical models and experimental observations supporting the knowledge around conditioned responses.


Donald Hebb

Donald Hebb in 1949 was one of the first to seize upon this observation.  He proposed that on the biological level, neurons were rewired so that coordinated inputs and outputs get wired together.  As such, were there a nausea neuron and a boat neuron, through the effects of association, the two would get wired together so that the “boat” itself fires up pathways in the “nausea” part of the brain.

In the field of neural networks, this has a name: Hebbian learning.  Pavlov of course also described this phenomenon, and tested it in animals, bequeathing its name the “conditioned response”.

Until now the wiring of neural inputs and outputs was a theory with good but indirect evidence.  At UCSD, neuroscientists teamed up with molecular biologists to engineer a mouse whose neurons can be directly controlled for forming and losing connections.

They did this by injecting an engineered virus into the auditory nerve cells.  The viruses, largely harmless, carry a light responsive molecular switch (a membrane protein “channel” actually) which gets inserted into cells of the auditory region.  Using laser light of certain frequencies it is possible to both “potentiate” or “depress” the auditory nerve cells.

The upshot is that the researchers could directly make the auditory nerve cells increase or decrease their signal strength to other nerve cells, without needing a real, external noise.  In effect, they’ve short-circuited the noise input.  In experiments, they used a light electrical pulse to shock mice while simultaneously stimulating the auditory input with the laser-activated switch.

Basically they flashed the laser light at the ear of the mouse.  Over time, the mouse began to associate the laser pulse induced nerve signal with the electrical shock.  The mice were conditioned to exhibit fear even when there was no shock.

The crux of the experiment is what happened when the scientists flashed the laser in a way to weaken the auditory nerve.  Now the mouse stopped responding in fear to the laser auditory stimulus.

The experiments showed for the first time that associative learning was indeed the wiring together of sensory and response neurons.  The study was published in Nature.

*Nature (2014) doi:10.1038/nature13294

(Photo Credit: Karl Deisseroth)

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