New molecular tool can be used to study unique synapses of neurons

Neurons are the primary cells of the nervous system, and the signals transmitted between them are responsible for all of our actions and cognitive abilities. In particular, it is believed that learning and memory are associated with a process called “long-term potentiation,” which is the strengthening of connections between specific neurons via continuous transmission of the signal through “synapses” (small spaces between neurons). Long-term potentiation can change the connection between neurons through synapses – changing their size and composition. Understanding how long-term potentiation occurs can be helpful in clarifying how our brains learn and retain new knowledge. A team of Japanese scientists have now made significant progress in understanding long-term potentiation. Read on to find out how!

One way to study long-term potentiation is to use “optogenetics”, that is, by activating neurons and monitoring their responses to light stimulation. Optogenetics allows scientists to activate single neurons and dissect the functioning of neurons in neural networks. As such, optogenetics is a revolutionary advance in neuroscience research, but optogenetic tools to modify single synapses (spines) have not been developed until now. This is a problem because neural signaling pathways can have effects specific to the spine. In particular, the protein “CaMKII”, critical for long-term potentiation, is activated by the “glutamate” molecule in a way specific to the spine, but what exactly happens at the synapses during activation. remains a mystery.

Fortunately, a research team from the National Institute of Physiological Sciences of Japan, led by Dr. Hideji Murakoshi, solved this problem. The team fused CaMKII with a specific domain of a plant photoreceptor (a type of cell that responds to light). This domain called “LOV2-Jα” made CaMKII light sensitive, after which they expressed this new photoactivatable CaMKII in different types of isolated neurons and in living mice. Their results are recently published in the journal Nature communications.

“We were very happy to see that activation of CaMKII triggers important effects, in particular the recruitment of receptors which cause a chain reaction which then leads to long-term potentiation,” explains Dr Murakoshi. The process physically alters the dendritic spines, dilating them, a result scientists have also observed in their experiments. Importantly, all that was needed for this process to occur was the activation of CaMKII – to put it in scientific terms, the activation of CaMKII was sufficient for the long-term potentiation of individual dendritic spines, which did not. not been shown before. The team also used light-based imaging technology and light-activated CaMKII to determine which signaling molecules are activated during long-term potentiation. All of these results combine to provide a better picture of how long-term potentiation occurs at the synapse.

“In addition to the valuable information we have discovered about an important neurological process, our light-activated CaMKII is a major addition to existing optogenetic tools,” comments Dr Murakoshi, when asked about the importance of their work. “We have created something that can be used to manipulate neural signaling and study synaptic plasticity – or the physiological changes that occur at individual synapses during events like memory formation.”

Scientists are optimistic that with further development the ability to manipulate synapses also has important implications for the treatment of diseases of the brain (such as autism) – a remarkable feat for neuroscience!