麻豆AV

Unlike old dogs, old adults can indeed learn new tricks thanks to a protein molecule called netrin.

Netrin is known to help set up the healthy nervous system in an infant鈥檚 developing brain by directing brain cells to make appropriate connections with other brain cells. New research conducted by scientists at The Neuro has found that netrin in the adult brain can make neural connections stronger, which is crucial not only for learning new tricks but also for maintaining a good memory.

鈥淚t was a mystery why neurons would continue making netrin in the adult brain after all the connections had already been made in infancy,鈥� says Timothy Kennedy, a researcher at The Neuro and senior author of the paper published in the Oct. 2 edition of Cell Reports. 鈥淲e found that when a neuron is active, the activity causes it to release netrin. The netrin acts to strengthen the connection between the neuron and a neighbouring neuron at the activated synaptic junction. Netrin鈥檚 essential signal to the two neurons is 鈥楳ake the synapse stronger.鈥欌��

The notion that synaptic activity itself could influence the strength or weakness of synaptic connections was proposed many years ago by 麻豆AV鈥檚 Donald Hebb. In 1949, Hebb postulated that if one neuron helped to fire another neuron, the two neurons consequently became associated. Many neurons firing together in a correlated way then form a circuit capable of cognitive processes. Hebb鈥檚 theory offered a novel physiological explanation for processes such as learning and memory.

鈥淲e鈥檙e saying that this new molecular mechanism, which we discovered 69 years later, is central to this theory,鈥� says Dr. Kennedy.

In 1957, neuroscientist Brenda Milner of The Neuro published a seminal paper in which she established the importance of the hippocampus for certain types of learning and memory. Much subsequent study has focussed on the hippocampus and the complex activity that occurs at the synapse.

鈥淚f you boil it down to one molecule,鈥� says Kennedy, 鈥渢he regulated release of netrin is essential for the kind of synaptic changes that underlie the changes in the neuron that are involved in learning and memory, which was what Milner was talking about.鈥�

Stephen Glasgow, a research associate at The Neuro and lead author on the Cell Reports paper, calls the work on netrin 鈥渁 huge step forward in identifying how the brain makes and stores memories. Our research demonstrates that netrin is critical for changes in the strength of connections between brain cells, and offers a new, previously undiscovered target for diseases that affect memory function.鈥�

Although there is genetic evidence implicating netrin in many neurodevelopmental and neurodegenerative diseases such as Alzheimer鈥檚, Parkinson鈥檚 and amyotrophic lateral sclerosis (ALS), it is far from clear how netrin might be involved.

鈥淲e鈥檝e identified a huge target for drugs,鈥� says Kennedy. 鈥淚f you want to save memory function, an ideal thing would be to have a compound that targets key molecular mechanisms at the synapse. Recent research has shown that many synaptic connections in the adult brain are turned off, like light bulbs that are not on. They鈥檙e healthy, just not on. Perhaps there is a reservoir of synapses that can be used to change the strength of connections between neurons. We believe that we鈥檝e found a molecular mechanism to turn on those synapses.鈥�

Co-author Edward Ruthazer, another investigator at The Neuro, notes that "it鈥檚 particularly interesting that this synaptic strengthening appears to require the release of netrin into the extracellular space, providing a previously unknown opportunity for this signal to interact with other cells."

Kennedy and his colleagues are now conducting experiments to see how neurons react when netrin is removed or added.

In addition to The Neuro, research for the Cell Reports article was carried out at 麻豆AV and at the CERVO Brain Research Centre of Universit茅 Laval.

View the original research paper (open access):