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Image shows neurons in the region of the olfactory bulb on a section of the brain of a young mouse. The different colors help to better understand the development of neurons in the brain of the mouse after birth. The concomitant presence of green fluorescence and red or orange fluorescence in a cell makes it possible to determine whether the newly produced neuron (in green) is a dopamine neuron ( red) or calretinin (orange). The blue simply indicates the nucleus of all the cells present in the image.
The production of neurons
Until the middle of the XXth century, one of the major dogmas of neuroscience considered that neurons were made only before birth, during the development of the nervous system. Therefore, the adult brain could only lose it as it grew older. However, since the years 07, this dogma has been reversed by studies which have proven the existence of stem cells in the brains of several organisms such as birds, fish and mammals. Stem cells are “mother” cells capable of giving rise to all cell types in an organism. They can persist into adulthood in different tissues or organs before eventually differentiating, that is to say forming specific cells of the organ in question – in this case, the brain.
It is now well established that certain types of neurons continue to be produced from these stem cells throughout life. In mammals, two particular regions are affected by the continual supply of new neurons: the hippocampus, seat of control memory and learning, and the olfactory bulb, essential for decoding olfactory sensory information from the external environment.
This cellular renewal would allow an adaptation (or “plasticity”) of the neuronal circuits to new information. What is more, stem cells would also constitute a cellular reservoir capable of being reactivated in a pathological context during brain damage to precisely redirect the production of neural cells (neurons and glia) towards the damaged region.
Behind the generic term neuron hides in fact a large variety of cell types, with different morphologies and different functions. One of the enigmas of neurogenesis is therefore to understand how stem cells of similar appearance can generate such a diversity of neurons. Genes have an important role to play in this process, and it is therefore essential to determine which are required to make one type of neuron rather than another. This knowledge is particularly crucial for developing therapeutic approaches which would consist of diverting stem cells from their normal function to force them to produce new neurons to replace those damaged by pathology, in the case of a neurodegenerative disease for example.
The function of genes
How to identify the function of a gene in the formation of neurons? It suffices to modify the activity of this gene in the stem cells, either by abolishing it or by increasing it, and to observe the effect of the modification on the future of the stem cells: what type of neurons are- they then able to produce?
In mice, it is possible to introduce a gene, or a molecule that inactivates this gene, directly and precisely into certain stem cells of the brain in the animal alive, those which produce the neurons of the olfactory bulb. And to be able to identify the cells thus modified, a gene coding for a fluorescent protein is simultaneously introduced into the same cells – in the case of this image the “GFP” (for “Green Fluorescent Protein»). It is then sufficient to follow the fate of the green cells in the olfactory bulb, and to identify the type of new neurons generated.
For this study, the tissue was treated with two fluorescent antibodies (red and orange) to reveal the presence of specific proteins in the cells, each antibody interacting with a particular protein. The red and orange cells correspond respectively to two subtypes of neurons present in the olfactory bulb: dopamine neurons (neuromediator) and calretinin (calcium-binding protein) neurons. The green cells correspond to new neurons produced from stem cells modified on the first day after birth, in which the fluorescent protein GFP has been introduced by genetic manipulation. A green and orange neuron indicates that this new neuron is a calretinin neuron, and a green and red neuron is a dopamine neuron.
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