Windows into the brain show how experience rewires neural circuitry

Researchers at the Howard Hughes Medical Institute (HHMI) have used a newly-developed technique to observe the growth of dendritic spines, and the consequent re-wiring of cortical circuits, in the brains of mice in response to new sensory experiences.

A strain of transgenic mice which express green fluorescent protein in a small number of neocortical cells was used for the experiments. GFP expression in the cells allowed for better visualization of the experience-dependent changes in the morphology of cells.  

Mice and other rodents are highly dependent on their whiskers for obtaining information about their environment.  A large part of the rodent brain, called the barrel cortex, is devoted to processing sensory information from the whiskers. The whiskers and barrel cortex together constitute the vibrissal system.

By selectively and repeatedly trimming whiskers, Karel Svoboda and colleagues provided the mice with novel sensory stimuli. Whiskers were trimmed to produce a 'chessboard' pattern, in which a trimmed whisker is surrounded by untrimmed whiskers.

The team removed pieces of skull overlying the barrel cortex, replaced them with thin coverglasses and used two-photon laser-scanning microscopy, aimed through the 'window' in the skulls of the mice, to observe the changes in fluorescence of layer L5B pyramidal  cells in response to whisker-trimming. 

The experiments, described in today's issue of Nature, show that the brains of the mice adapted to the loss of whiskers by the loss of some dendritic spines. The vibrissal system also generated large numbers of new dendritic spines on the cells receiving tactile stimuli from the remaining whiskers, which were required to process more information by way of compensation.  

spines.jpg (Nature)

The newly-formed dendritic spines were robust and persisted for the 28 days over which the imaging was carried out. Furthermore, electron microscopy revealed that the new spines had formed synapses with other cells, suggesting that their appearance had caused a re-wiring of the circuitry in the vibrissal system.   

The authors conclude that the new spines increase the number of synapses between cells that were already connected, and contribute to synapses between previously unconnected cells.

The study will provide more insights into how the plasticity of the brain underlies processes such as learning.