The image shows neurons in the region of the olfactory bulb on a section of the brain of a young mouse. The different colors allow us 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 manufactured neuron (in green) is a dopamine (red) or a calretinin (orange) neuron. Blue simply indicates the nucleus of all cells present in the image.
Does the brain produce neurons throughout life and why?
Until the middle of the twentiethe 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 as it ages. However, as early as the 1990s, this dogma was overturned by studies which proved 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 last into adulthood in different tissues or organs before eventually differentiating, that is to say forming cells specific to the organ considered – 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 concerned by the continual supply of new neurons: the hippocampus, seat of memory and learning control, and the olfactory bulb, essential for decoding olfactory sensory information from the environment. outside.
This cell renewal would allow an adaptation (or “plasticity”) of neuronal circuits to new information. What is more, stem cells would also constitute a cell reservoir capable of being reactivated in a pathological context during brain lesions to precisely redirect the production of neural cells (neurons and him) to the damaged area.
Behind the generic term neuron actually hides a wide variety of cell types, with different morphologies and 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 ones are required to make which neuronal type rather than another. This knowledge is particularly crucial for developing therapeutic approaches which would consist in diverting stem cells from their normal function in order to force them to produce new neurons to replace those altered by the pathology, in the case of a neurodegenerative disease for example.
How to identify the function of a gene in the formation of neurons?
By modifying the activity of this gene in stem cells, either by abolishing it or by increasing it, and by observing the effect of the modification on the fate of stem cells: what type of neurons are they then capable of to produce?
In mice, it is possible to introduce a gene, or a molecule that inactivates this gene, directly and precisely into certain brain stem cells in living animals, those which produce the neurons of the olfactory bulb. And in order to be able to identify the cells thus modified, a gene encoding a fluorescent protein is introduced simultaneously into the same cells, in the case of this image the “GFP” (green). 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: the dopamine neurons (neurotransmitter) and calretinin (calcium-binding protein) neurons. Green cells correspond to new neurons produced from modified stem cells on the first day after birth, into 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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