Published on January 28, 2013 at 4:40 AM
Knowing that the basal forebrain is implicated in learning, the researchers wanted to know if their observations could be explained by nerves from the basal forebrain delivering ACh to the vision-processing center. To remove those nerve cells from the equation, they paired a neurotoxin with a "homing device" that targets only ACh-releasing neurons coming from the basal forebrain. They then repeated their experiments in trained rats that received the neurotoxin and in those that didn't, and found that the nerve cell signals continued to relay the old time intervals, suggesting that ACh and the basal forebrain weren't needed to express previously learned time information.
The researchers next used those same rats to ask if ACh is necessary for nerve cells to learn new time delays. To do that, they switched the visual cues so that a flash in the left eye meant a long delay and one in the right eye meant a short one. Vision-processing nerve cells in the rats in which ACh delivery was left intact adapted their signals to the new associations; but those in the rats that no longer received ACh continued to relay the old associations, suggesting that ACh is necessary to make new associations but not to express old ones.
Hussain Shuler explains, "When a reward is received, ACh is sent throughout the brain and reinforces only those nerve cell connections that were recently active. The process of conditioning continues to strengthen these nerve connections, giving rise to a timed expectation of reward in the brain."
According to Hussain Shuler, studies have shown that Alzheimer's patients have low levels of ACh and have trouble forming new memories. Though medication may elevate ACh, alleviation of symptoms is limited. "Our research explains that limitation," he says. "Therapeutically, we predict that the problem isn't just low levels of ACh - the timing of ACh delivery is key."
Source: Johns Hopkins Medicine