An important breakthrough in understanding brain mechanisms that can help find new drugs for dementia explains how we learn new tasks and acquire new memories by a single protein on-off switch in the brain.

‘A single protein on-off switch in the brain controls learning flexibility and acquisition of new memories. This breakthrough discovery can perhaps explain why those living with dementia and Alzheimer’s disease have short term memory loss and struggle while adapting to new situations.
’

The findings, published in the journal Neuron, are led by Dr Sonia A.L. Correa from the University of Bradford and Dr Angela M. Mabb from Georgia State University in the US and in collaboration with Dr Mark Wall from the University of Warwick. They mark an important breakthrough in understanding the mechanisms in the brain that control cognitive abilities. 




The team already knew the importance of the protein Arc in learning and memory. Arc is a key protein in enabling synaptic connections and is switched on during learning and, when no longer needed, switched off rapidly.
They suspected that alterations in how Arc functioned would affect such cognitive abilities. To test this, the team created a genetically modified mouse that expressed a mutated form of Arc that only switched off slowly, but was otherwise behaviorally normal.
The mouse was then compared with a normal mouse in its ability to solve a maze, escaping at a certain point. Both mice were able to solve the maze and locate an escape hole. However, when the hole was moved to a new location, the normal mouse was again able to solve the problem rapidly and after discovering the hole's new position, could go straight to it on each successive occasion. However, the modified mouse had to rely each time on a serial strategy, going through every step to find the hole.
To make an analogy imagine you are staying at a hotel for a couple of weeks. After the first week, the manager changes your room but he won't tell you where your new room is located. To find your new room, you would have to test your key in each door until it opened your door.
Advertisement
Imagine instead a situation where each time you returned to the hotel you had to keep trying the key in each room door to find your room. This inability to adjust your strategy to find the location of your new room is known as cognitive inflexibility and, as we age, this altered behavior occurs more frequently. More importantly, this type of behavior is observed during ageing and in some forms of neurological conditions including Alzheimer's disease.
Advertisement
This study has given us the first clue about the molecular mechanism to reverse a learning process and to layer new information onto previously learned information.
Dr Sonia Correa, from the University of Bradford, said: "These findings show that activity of a single molecule controls a critical aspect of learning and memory process, which is the ability to reverse a learning task. Remarkably, this molecule is not implicated on the learning process itself, but rather on the reversal learning. As such these findings give us hope to develop specific therapeutic drugs aimed to delay deficits in reversal learning that is believed to cause the early loss of memory that occurs in ageing and neurodegenerative diseases."
Dr Angela Mabb of Georgia State University said: "It's scary to think that the abnormal removal of one single protein [Arc] in the brain can cause this type of altered behavior. We are currently conducting new experiments in the lab to look at this more closely with the goal of identifying novel drug targets for neurological conditions like Alzheimer's disease, which are known to have cognitive inflexibility."
The team believes it now has a robust model on which to base pre-clinical trials looking at how to target the relevant pathways to override the malfunctioning of the Arc protein.
Source-Eurekalert