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Sunday, March 3, 2024

Negative feedback is a plus

The brain is one of the most fascinating and intricate structures in the human body. One of its most basic functions is to store information in the form of memory. In a study published August 18th in the journal Nature Neuroscience, Mark Goldman, joint professor in the Neurology, Physiology and Behavior Department at UC Davis and the Department of Ophthalmology and Vision Science at the UC Davis Medical Center, and Sukbin Lim, a postdoctoral researcher at UC Davis, explored how negative feedback mechanisms stabilize memories against the test of time.

According to Goldman, one essential question neuroscience researchers have been trying to figure out is how neurons, which typically only remain activated for very short amounts of time, can maintain memories over long periods.

“The classic explanation for how neurons can respond for the many seconds that we can maintain an item in mind during short-term memory is that neurons may be interconnected through positive feedback loops,” Goldman said in an email.

A positive feedback loop is when a disturbance to a set point causes a reaction that, in turn, amplifies the disturbance. In this case, nerve cells being activated in response to a stimulus would cause a loop that maintains the firing of nerve cells, thus enabling us to “remember” that stimulus.

However, Goldman and his team believe that positive feedback alone is too unstable to maintain memories in the long run. Without a system of checks and balances, the positive feedback could go on indefinitely and amplify, potentially leading to some disastrous consequences, much in the way that speaking into a microphone too loudly produces that awful screeching sound.

This is where negative feedback comes in. Where positive feedback tries to amplify a signal, negative feedback works to prevent the strength of a signal from becoming weaker or stronger.

“The key idea of our model was to show that the circuitry of memory-storing regions of the brain’s neocortex may include ‘slip detectors’ that detect when a memory representation is changing — either growing, as in the microphone screeching example, or decaying to zero, which would cause the memory to be quickly forgotten — and use negative feedback to offset this ‘memory slip’”, Goldman said.

In order to simplify the unfathomably complex connections that nerve cells in the brain make with each other, scientists often think of them as if they were circuits in a computer. Goldman and his team took advantage of this fact and utilized mathematical models that mimicked such circuitry. In doing so, he was able to demonstrate the viability of his proposed model.

“We may have identified a fundamental building block of memory storage, at the level of neural circuitry.  Hopefully, future work can build up from this finding to start to put together how we store more complex information,” Goldman said.

Though this finding marks a substantial step forward in better understanding memory at the most fundamental level, on a more macroscopic scale, we are still more in the dark than we would like to be.

According to Charan Ranganath, a memory researcher and professor for the Psychology Department at UC Davis, the most challenging part of studying memory is that experts cannot agree on what exactly they are studying. He said there is a general consensus in the field that there are multiple types of memory, and that those multiple types of memory should correlate to different areas in the brain. However, exactly how many types of memory and exactly where they are located remains up for debate.

“I might think that I am measuring one form of memory, but in fact use a measure that is sensitive to different kinds of memory. It would be like a physicist or a chemist running an experiment and not being sure whether s/he is measuring heat, light, sound or some combination of these factors,” Ranganath said in an email.

Fortunately, dedicated researchers such as Goldman and Ranganath are doing everything they can to further understanding. By doing so, they enable us to have a better grasp on our own minds and potentially develop new techniques for treating people with memory disorders.


KYLE SCROGGINS can be reached at science@theaggie.org.


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