A team led by Susumu Tonegawa, a professor at MIT’s Picower Center for Learning and Memory, are using a new technique to investigate, in real time, plasticity in the cortices of mice in response to visual stimulation.
Tonegawa and his colleagues first produced transgenic mice in which a portion of the mouse Arc gene was replaced with green fluorescent protein (GFP). It is known that transcripts encoding the Arc protein accumulate in the dendrites at sites of recent synaptic activity, and although the function of Arc is unknown, it is believed to play a role in the formation of new synaptic connections.
Small openings were made in the portion of the animals’ skulls overlying the visual cortex; these openings were covered with glass to create ‘windows’ into the brains of the mice. The mice were then exposed to various visual environments, and two-photon microscopy was used to observe the changes in fluorescence that occurred as a result. Because part of the Arc gene had been replaced with the GFP sequence, these changes were indicative of Arc expression.
Two strains of transgenic mice were created; in one strain, one copy of the Arc gene was replaced with GFP, and in the other both copies were replaced. A comparison of the two strains therefore provided clues about the function of Arc – it revealed that mice retaining one copy of the Arc gene responded more specifically to stimuli they had previously been exposed to.
“This is the first time we can look at the molecular activity inside individual cells in response to a sensory experience,” says Kuan Hong Wang, who is lead author of the paper describing the work.
Strictly speaking, that’s not true. Exactly two months ago, I wrote about a group at Howard Hughes Medical Institute (HHMI) who used exactly the same technique to look at the rearrangement of dendritic spines in the brains of mice after whisker-trimming. That group also used transgenic mice expressing GFP.
The main difference between the two studies is the site that was investigated – the HHMI looked at changes in the vibrissal organs of mice in response to novel sensory experiences caused by whisker trimming, whereas the MIT team looked at changes in the visual cortex in response to new visual stimuli.