Northwestern Medicine scientists have identified a region of the brain associated with the recollection of long-term memories.
Led by Craig Weiss, PhD, research associate professor in Physiology, investigators determined that a sub-region of the prefrontal cortex is activated in learning a conditioned response. The classic example of a conditioned response involves Pavlov’s dogs, which would salivate at the ringing of a bell in anticipation of the learned connection between the noise and food.
“We’re now trying to find the neuronal mechanisms that underlie that learning,” said Weiss, a scientist in the lab group of John Disterhoft, PhD,Ernest J. and Hattie H. Magerstadt Memorial Research Professor of Physiology. “Using electrodes, we recorded the responses of many neurons simultaneously to discover what regions of the prefrontal cortex are activated during this learning process.”
The findings were recently published in the Journal of Neuroscience.
For more than five decades, investigators have used a method of conditioned response that revolves around delivering a tone before a mild puff of air to the eye, causing a blink. After a cycle of tone, puff, tone, puff, the animal will blink when the tone is delivered in expectation of the puff. This response illustrates that the association has been learned.
To uncover how the brain stores and recalls long-term memories, Weiss, postdoctoral fellow Taejib Yoon and Shoai Hattori, a student in the Northwestern University Interdepartmental Neuroscience PhD Program, taught rabbits the conditioned response by tapping their sensitive whiskers – rather than using a tone – before delivering a puff of air. After conditioning the animals, the scientists waited 30 days and monitored brain activity when the rabbits recalled that a whisker tap predicted the air puff.
“The most impressive result from this paper is that the prelimbic region had this robust activity when we looked at it 30 days after the behavior was learned,” Weiss said. “The activity in this part of the brain was not present during the initial learning and it’s not there in the controls, meaning its highlighting some aspect of the memory process.”
What the scientists aren’t able to discern is if those neuronal signatures are the actual memory of the task or a reflection of the mechanism that executes the conditioned blink.
The lab previously discovered that another part of the prefrontal cortex, the caudal anterior cingulate (cACC), is extremely responsive during the first few learning sessions, suggesting that this part of the brain is involved in attention.
“We found that after a 30 day training hiatus, activity in the cACC goes down and activity in the prelimbic cortex goes up,” Weiss said. “This seems to illustrate that the brain transitions from an attentive state to a remembering state within this timeframe.”
The Disterhoft lab will next look at the process of conditioned response in aging. Investigators hope to identify the different ways cognitive impairment and age affect the brain’s wiring.
“The continuation of this project will ultimately allow us to test different drugs being developed to improve cognition and age-related cognitive decline,” Weiss said.
The research was supported by National Institute of Mental Health Grants F31MH099769 and R01MH47340; National Institute on Aging Grants 5T32AG020418 and 5T32AG020506; and National Institute of Neurological Disorders and Stroke Grant R01NS059879.
