For the first time, researchers have observed the Pavlovian response in mouse brains as it happens, thanks to new biosensor technology that can detect how chemical messengers called neurotransmitters are distributed around the brain.
While this technology will likely see wider use down the road, the team is currently using it to gain a better understanding of how addiction operates in the brain.
"We developed cell-based detectors called CNiFERs that can be implanted in a mouse brain and sense the release of specific neurotransmitters in real time," said team member Paul Slesinger, from the Icahn School of Medicine at Mount Sinai.
CNiFERs – which stands for 'Cell-based neurotransmitter fluorescent engineered reporters', and is pronounced "sniffers" – are a type of biosensor that can be implanted into an animal’s brain.
They emit light to differentiate between two neurotransmitters: dopamine and norepinephrine, which are signifiers of pleasure and alertness.
Before CNiFERs, researchers were hard-pressed to study these two neurotransmitters in real time, because they look so similar in current imaging technology. Instead, researchers analysing brain activity often use fMRI techniques to analyse blood flow in different regions, Katherine Ellen Foley reports for Quartz.
Now, with the development of CNiFER biosensors, researchers can accurately monitor the actual chemicals – not the blood flow – in the brain by observing the light they emit through a two-photon microscope. This allows them to observe when certain neurotransmitters appear in real time.
To test the sensors, the team revisited Pavlov’s famous dog experiment, in which the Russian scientist conditioned dogs to salivate when they heard a bell, because they knew it meant they would get food. This time, though, the team tried it out on mice.
This involved playing a specific tone, waiting a short while, then rewarding the mice with sugar.
As they repeated this process over the course of a few days, the team found that the tone caused the mice to salivate in anticipation, just like Pavlov’s dogs did.
"We were able to measure the timing of dopamine surges during the learning process," said Slesinger. "That's when we could see the dopamine signal was measured initially right after the reward. Then after days of training, we started to detect dopamine after the tone but before the reward was presented."
The research comes with a couple of caveats. The findings were recently presented at the 252nd National Meeting and Exposition of the American Chemical Society, but have yet to be published in a peer-reviewed journal. And so far, the CNiFERs only work on mice.
But as the technology improves, and the experiment is replicated by other researchers, it could give us better insight into how classical conditioning can change the pathways of the brain.
Not only could that push us further in our understanding of how learning and addiction works, it could also lead to better treatment for those with disrupted neural pathways, such as patients with Parkinson’s disease