Single-neuron Observations Mark Steps

Photo: Beta-amyloid plaques

The study sheds light on what is
happening in the brain throughout
the disease process; © TUM/
Christine Grienberger

In addition to its well known, devastating effects on memory and learning, Alzheimer's disease can also impair a person's sense of smell or vision. Typically these changes in sensory cognition only show themselves behaviourally when the disease is more advanced. A new study sheds light on what is happening in the brain throughout the disease process, specifically with respect to the part of the cerebral cortex responsible for integrating visual information. A team led by Professor Arthur Konnerth has observed Alzheimer's-related changes in the visual cortex at the single-cell level.

Using a technique called two-photon calcium imaging, the researchers recorded both spontaneous and stimulated signalling activity in cortical neurons of living mice: transgenic mice carrying mutations that cause Alzheimer's disease in humans, and wild-type mice as a control group. By observing how neuronal signalling responded to a special kind of vision test – in which a simple grating pattern of light and dark bars moves in front of the mouse's eye – the scientists could characterize the visual circuit as being more or less "tuned" to specific orientations and directions of movement.

Konnerth explains, "Like many Alzheimer's patients, the diseased mice have impairments in their ability to discriminate visual objects. Our results provide important new insights on the cause that may underlie the impaired behaviour, by identifying in the visual cortex a fraction of neurons with a strongly disturbed function."

And within this group, the researchers discovered, there are two subsets of neurons – both dysfunctional, but in completely different ways. One subset, thought to be the first neurons to degenerate, showed no activity at all. The other showed a pathologically high level of activity, rendering these neurons incapable of properly sensing objects in the mouse's environment. "While around half of the neurons in the visual cortex were disturbed in one way or the other, roughly half responded normally," says Christine Grienberger. "That could have significant implications for future research in the field of Alzheimer's disease, as our findings raise the question of whether future work only needs to target this population of neurons that are disturbed in their function."

MEDICA.de; Source: Technische Universitaet Muenchen