Excitatory (E) neurons hold the memory. If their activity begins to slip, fast negative feedback (red) mediated by inhibitory (I) neurons can correct this slip before slower positive feedback loops (blue) bring the circuit back into balance. (UC Davis graphic)
The work was published Aug. 18 in the journal Nature Neuroscience.
“The puzzle out there is: How do brain circuits retain a memory without it slipping?” said Associate Professor Goldman. “For example, if you store a memory of the color yellow, why doesn’t it slip over time into orange?”
Earlier models used positive feedback to maintain memories. The idea is that, if a memory starts to fade, the circuit gets a boost.
“The problem with positive feedback is that, without some additional mechanism, it’s brittle — the system doesn’t respond well to being perturbed,” said Goldman, who also holds joint appointments in the Department of Neurobiology, Physiology and Behavior within the College of Biological Sciences, and the Department of Ophthalmology and Vision Science within the School of Medicine.
Goldman and Lim, a postdoctoral researcher, thought that these brain circuits might instead be doing something an engineer would do — stabilizing a system with negative feedback. For example, a thermostat uses negative feedback to turn on heating or cooling depending on whether a room’s temperature drifts below or above a set point.
The researchers built mathematical models to simulate the kinds of neural circuits found in the cortex of the brain. Neurons are connected to each other through junctions that transmit either positive (excitatory) or negative (inhibitory) signals.
The modeling studies show that negative feedback can stabilize these circuits and allow them to store memories. What’s more, the models show that these circuits should be robust to perturbations such as death of individual cells.
“Biological systems tend to be robust, so we wanted our models to reflect this robustness,” Goldman said. The models also reflect key features of the circuitry observed in the brain’s neocortex, he said.
Lim and Goldman further showed how positive feedback and negative feedback could work together in the same circuit, demonstrating how the brain may exploit multiple mechanisms to store memories.
Lim is now a postdoctoral researcher at the University of Chicago. The work was supported by the National Institutes of Health and a Sloan Foundation Research Fellowship to Goldman.
About UC Davis
For more than 100 years, UC Davis has engaged in teaching, research and public service that matter to California and transform the world. Located close to the state capital, UC Davis has more than 33,000 students, more than 2,500 faculty and more than 21,000 staff, an annual research budget of nearly $750 million, a comprehensive health system and 13 specialized research centers. The university offers interdisciplinary graduate study and more than 100 undergraduate majors in four colleges — Agricultural and Environmental Sciences, Biological Sciences, Engineering, and Letters and Science. It also houses six professional schools — Education, Law, Management, Medicine, Veterinary Medicine and the Betty Irene Moore School of Nursing.
- Mark Goldman, Center for Neuroscience, (530) 757-8749, [email protected]
- Andy Fell, UC Davis News Service, (530) 752-4533, [email protected]