Christiaan Levelt poseert voor een foto.

Levelt Group

New software tool for the analysis of calcium signals in brain cells

The combination of modern microscopy and DNA techniques has revolutionized brain research over the past 10 years. It is now possible to visualize the activity of hundreds of individual brain cells in mice during behavioral tasks. This can be done over periods of weeks to months, showing how brain cells process information and how this changes as the animals learn.

One of the most powerful ways to do this is by introducing DNA into brain cells that encodes a fluorescent protein. This protein changes fluorescence intensity when it binds to calcium. Since calcium enters the cells when they are active, changes in fluorescence indicate firing of the brain cells.

Challenging analysis

A special microscope that can image deep into the brain allows monitoring of these changes in light intensity. This results in hours-long movies of hundreds of brain firing cells.  Understandably, it is a major challenge to analyse this information. Smart software is needed to automatically identify the brain cells (or their neurites), isolate their signals, filter out noise, and to find back the same brain cells on different days.

Several software tools are available that perform some of these tasks, but they are not always intuitive or user-friendly and do not offer all the necessary features in one package. Therefore, Leander de Kraker and Chris van der Togt have created a software tool in the Levelt lab that performs all these tasks and is easy to use. The software has been extensively tested and described in an article published in Cell Reports Methods.

The software can be downloaded for free via this link.

Link to paper



Christiaan Levelt poseert voor een foto.

Levelt Group

Plasticity of the neocortex is crucial for us to learn and adapt to our environment. Once tasks or functions are learned, the brain can carry them out very efficiently, in a routine-like fashion. However, learning and carrying out routine functions do not go hand in hand. During development the brain is highly malleable, but processes information rather slowly and erratically. Vice versa, when we perform routine tasks, little learning occurs and we ignore many inputs. This situation can suddenly change when a routine procedure results in an unexpected outcome. We rapidly become aware of additional circumstances and learn what caused the unexpected result.

Recent evidence, also from our laboratory, suggests that these increases in plasticity levels during critical periods of development or in response to reinforcement signals are achieved by a temporary reduction in cortical inhibition. Possibly, high levels of inhibition increase performance of neuronal networks by suppressing inputs that are irrelevant for the execution of routine tasks. Reduced inhibition may support learning by allowing such inputs to be taken into consideration to solve a novel challenge.

Using the mouse visual cortex as a model, the Levelt lab studies how inhibition regulates cortical plasticity levels at the right time. To achieve this goal the lab employs a combination of state-of-the art two-photon microscopy, electrophysiology, optogenetics and gene manipulation.

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