Surprised? Cholinergic neurons send brain-wide broadcasts enabling us to learn from the unexpected
News Aug 27, 2015
When a large combat unit, widely dispersed in dense jungle, goes to battle, no single soldier knows precisely how his actions are affecting the unit's success or failure. But in modern armies, every soldier is connected via an audio link that can instantly receive broadcasts -- reporting both positive and negative surprises -- based on new intelligence. The real-time broadcasts enable dispersed troops to learn from these reports and can be critical since no solider has an overview of the entire unit's situation.
Similarly, as neuroscientists at Cold Spring Harbor Laboratory (CSHL) have just discovered, there are a set of dedicated neurons in the basal forebrain that broadcast a message throughout the cerebral cortex, rapidly informing multiple distributed subregions of any surprising rewards or punishments -- what scientists call reinforcers.
The neurons in question are cholinergic, and the team, led by Associate Professor Adam Kepecs, has succeeded in recording their activity for the first time in behaving animals (mice).
Cholinergic neurons form one of the brain's several neuromodulatory systems -- they send signals in the form of the neurotransmitter acetylcholine to broad swaths of the brain. Although they have been thought to play an important role in arousal, attention and learning, their precise role in behavior has remained mysterious -- in part, because of the technical difficulty in recording from them in vivo. Degeneration and loss of cholinergic neurons in the basal forebrain has been implicated in Alzheimer's disease, age-related cognitive decline, and other cognitive disorders and dementias.
In a paper published in Cell, Kepecs and colleagues report on how central cholinergic neurons function, using optogenetic neuron identification --a technique in which mouse neurons are genetically engineered to respond to light. "These are very, very, difficult-to-find neurons, and they form an incredibly important system in the brain," Kepecs says. "Until recently we didn't have the techniques to approach this system with the precision required."
Once they identified cholinergic neurons, the team recorded their activity while mice performed a sound detection task requiring sustained attention. Depending on whether their response was correct or not, mice were either rewarded with drop of water or "punished" with a mild puff of air to their face. Postdoctoral fellow Balazs Hangya of the Kepecs lab discovered that these neurons respond to reward and punishment, with unusual speed and precision, taking only a few thousandths-of-a-second.
To explain the responses researchers constructed a computational model which revealed that the modulation of the signal strength was proportional to how unexpected or surprising the mice found the reward or punishment. According to the model, if the mice were certain their response was correct, the reward generated a weak signal. But if they were unsure, the reward came as more of a surprise and generated a stronger cholinergic signal. "This suggests to us that it's not really about punishment, per se, but it's simply that punishment usually is more surprising," Kepecs says.
Kepecs suggests that cholinergic broadcasts to the cortex would be useful in boosting plasticity, allowing flexibility in neuronal connections that makes learning possible. Whether the surprise registers an outcome or event that was better or worse than expected, the fact it was unexpected, and the degree to which it was, is an obvious advantage to the individual -- as, indeed, constant intelligence is to soldiers in the unit enmeshed in jungle combat.
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Kepecs A et al. Central Cholinergic Neurons Are Rapidly Recruited by Reinforcement Feedback. Cell, Published August 27 2015. doi: 10.1016/j.cell.2015.07.057
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