Unravelling the secrets of the brain’s smallest cells

UCL scientists have made the first ever recordings of the brain’s smallest cells at work sensing the outside world. Their findings could help unlock the secrets of the cerebellum, a key motor control centre in the brain which, when damaged, can lead to movement disorders such as ataxia and loss of balance.

Paul Chadderton and colleagues at UCL’s Wolfson Institute for Biomedical Research used a method called patch-clamping to measure the activity of a single granule cell in an intact brain. The findings are published in the latest issue of Nature.

Granule cells are tiny. Their size – 20 times smaller than a human hair – has made it extremely difficult for scientists to study them in action.

Granule cells make up the input layer of the cerebellum and receive sensory information from the body, for example when a finger touches a surface. The cerebellum is thought to act as a link between the body’s senses and its movements, such as guiding the finger across a surface smoothly and efficiently. However, scientists still know very little about how the cerebellum does its job.

The group’s findings could ultimately help researchers understand more about movement disorders and potentially help in the development of drug treatments targeting the cerebellum, for example for sufferers of ataxia, a movement coordination problem which affects 150,000 people in the US, and dysmetria, where patients have difficulty regulating the rate, range and force of movement.

The group also found that the activity of granule cells is kept in check by a ‘tonic inhibition’ mechanism. There is growing evidence that alcohol can boost this inhibition and thus affect cerebellar function, possibly accounting for the drunken swaying and unsteadiness often associated with inebriation.

By applying the patch-clamp technique, where a cell membrane is gently sucked onto a glass pipette which records small electrical signals coming from the cell, UCL researchers were able to see the granule cell layer at work, confirming predictions made over 30 years ago by the celebrated English theoretical neuroscientist David Marr.

Marr suggested that the layer uses a sparse coding scheme to represent sensory input, where the firing rate of the cells is low in order to maximize the number of different patterns of sensory input that can be represented by the cerebellum. In other words, the cells keep their activity low to ensure that they remain sensitive to every type of sensation that is being picked up.

Paul Chadderton says: “We’re delighted to provide the first evidence of a theory born thirty years ago, namely that activity in cerebellar granule cells is dampened to maximise the brain’s capacity to represent many different sensations.”

“Neuroscience can now move forward with this technique, not only to better understand the brain, but ultimately to help those suffering from movement disorders. The more we understand about cell signalling, the better we can become at targeting drugs in complex parts of the brain.”