Almost everyone is familiar with the unique mixture of surprise and confusion that occurs after making a mistake during an everyday movement. It's a fairly startling experience stumbling on a step or accidentally missing your mouth when taking a drink.

This momentary bewilderment is due to the fact that our brains have an extraordinary capacity for learning skilled movements. So much so that our routine actions, such as climbing stairs, become second nature. For the most part, we don't even consciously think about them that is until we make a mistake.

While mistakes don't occur very frequently once we've picked something up, they are the tool used by the brain to evaluate and adjust our movements in hopes that next time, we won't stumble or spill our drinks so easily. 

Researchers have discovered part of the answer to this longstanding question. It is a much more complex behavior that can vary in duration, magnitude, and direction.  Our findings demonstrate that in the cerebellum, motor learning can occur along a continuum and what seems to be the key, is the influence of an inhibitory cell class called molecular layer interneurons.

Anatomy Of Brain

An anatomically unique region of the brain, the cerebellum plays a critically important role in regulating motor control and coordination. Despite its relatively small size- only about 10% of the entire brain- the cerebellum houses roughly half of our total neurons, around 50 billion. 

Behavior Learning

While receiving many inputs from various regions of the brain, the cerebellum integrates and sends refined information out through a single type of specialized neuron called a Purkinje cell. These cells receive two well-characterized excitatory inputs and a lesser studied inhibitory input, helping to guide motor behavior and facilitate learning.

When we make a mistake, however, a second excitatory input from a climbing fiber arrives simultaneously and delivers an instructive signal. This new information detailing motor error weakens the synaptic connections between parallel fibers and Purkinje cells; producing a change in behavior and ultimately allowing for learning to occur. But the function of inhibitory inputs in this process was still largely unknown.

Synaptic Plasticity

This alteration in synaptic strength, known as synaptic plasticity, is thought to be the mechanistic correlate of learning. Uncovering how inhibitory interneurons influence plasticity is the first step in gaining insights into their role in motor learning.

They found that inhibition allows for an entire spectrum of outcomes. By strongly activating molecular layer interneurons, there was a complete reversal of plasticity where synapses were strengthened with the addition of inhibition. 

Vestibular-Ocular Reflex

Taking the investigation one step further, inhibition produced a similar type of reversal on learning behavior. Using dual color optogenetics, the MPFI researchers evaluated the effect of molecular layer activation during adaptive vestibular-ocular reflex or VOR, which helps to maintain a stable gaze by moving the eyes in the opposite direction of head movement. 

Consistent with plasticity findings, strong activation of MLIs produced a complete reversal in learning of VOR, causing dramatically less eye movement (gain decrease). Inhibition seems to dramatically broaden the range with which cells can respond to stimuli. Instead of the brain having only two options -learning or not learning- there can be a tremendous amount of variation in between.