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    How Brains Wire Themselves to Expect Treats

    Written by

    Derek Mead

    Editor-In-Chief

    One of the most important aspects of our memory is our ability to predict what may happen in a given situation based on our past experiences. That we remember outcomes based on visual cues is incredibly important evolutionarily; if you can predict something is good or bad based upon what you've seen before, you've got a huge leg up on someone who can't. Yet while we can look at a pizza and immediately know that we want that tasty treat, how does that memory form?

    That question is at the root of a study led by Dr. Marshall Hussain Shuler of Johns Hopkins, to be published in Neuron. Hussain Shuler's team, which also included members from MIT, designed a study that looks at how memories are formed by looking at how rats connect visual stimuli with expectations of receiving treats. 

    First, let's discuss those awesome goggles the rat is wearing above. The research team designed the goggles to flash light in either of a rodent's two eyes. If the light flashed in the rat's left eye, it would only have to lick a water spout a few times before receiving water; if it flashed in the right, it'd have to lick the spout for a lot longer before getting water. The team found that, after conditioning the rats, they would  leave the spout if they didn't receive water in the expected amount of time, which suggests that their visual memory is connected to their reward expectations.

    The research team wired the rodents' brains to measure electrical impulses during the study, and found that signal spikes initiated by the visual cue–basically, the brain saying "water incoming!"–didn't occur just during the initial flash of light, but lasted as long as the rat expected to wait until the water started flowing. That suggests the entire cue-and-reward event is key to developing memory; the rat doesn't just get a flash of light and start waiting for water, but also has heightened expectations for the period of time it's learned to wait for until receiving the reward. This is key for survival, as the rat knows how long to wait for an outcome that isn't always guaranteed, rather than waiting blindly or not waiting at all.

    (By the way, I couldn't resist asking Hussain Shuler about making the rat goggles. In an email, he responded "It’s a lot of fun to develop the tools to do science. That’s half the thrill!" Awesome.)

    But how does that connection form? As with most things in the brain, it's chemical. The team found that neural connections in the vision-processing of the brain are strengthened by the release of a neurochemical called acetylcholine (ACh), which is believed to be released when an individual scores a treat. 

    Put more simply, when rodents received a reward, their brains appeared to release chemicals that strengthened the connection between that reward and its visual memory of what preceded the reward. The team tested it by switching the delay times after a light flash (now left was long, right was short) and blocking the release of ACh in some of the rodents. The rodents who were able to produce ACh re-learned the scenario, while those that couldn't did not produce new memories.

    A key part of this is the temporal aspect of ACh. The team found that ACh only strengthened neural connections (i.e., what forms memory) in neurons that were recently active. Because ACh is released throughout the brain, this may be key in making sure ACh only strengthens memories that are currently relevant, and suggests that visual information is key in rodents' ability (and because mammal brains are very similar, possibly ours as well) to developing memory.

    "Though the temporal precision of ACh signaling throughout the brain is not directly studied here, these results do suggest that the  precision of ACh timing is a key determinant in how the brain modifies itself, and that ACh may act as a reinforcement signal," Hussain Shuler said. "Reinforcement signals are thought, from a theoretical perspective, to best be served by brain systems that have a broad reach, common to neuromodulator systems like dopamine, norepinephrine, serotonin, including acetylcholine."

    According to Hussain Shuler, learning more about the temporal actions of ACh could help improve Alzheimer's treatments. ACh is already known to help cement memories, and Alzheimer's patients have been shown to have low levels of the neurochemical. Medications exist to boost production of ACh, but they haven't been consistently effective. This study suggests timing of ACh delivery is key, because ACh only strengthens memories as the happen, rather than boosting the brain's ability to create memories across the board.

    @derektmead

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