Study of glial cell function in brain synaptic networks

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The brain is by far the most complex organ of the human body and one of the most mysterious machines ever designed by nature. Besides controlling most vital functions, the central nervous system (CNS) is also responsible for every output produced by the organism. These outputs normally result from proper functioning of the cells with which it is composed, in particular the neuronal cells. These cells have the particularity of being active and responsive to the activity in the brain. There are different types of nerve cells, in particular those that convey the neuronal information towards a distant target and those that create a local network to regulate the activity all nerve cells of a given area. The cells that carry the information to a distant target are said to be excitatory as they will facilitate the activity of other nerve cells. The cells that regulate the network of nerve cells are often identified as inhibitory cells, as their role is to reduce the activity of other nerve cells.Nerve cells are responsible for the communication in the nervous system releasing chemical substance called neurotransmitters at specialised structures identified as synapses. A very important feature of the nervous system and its components is that they express a propensity to change with previous brain activity, providing the cellular basis for learning and memory formation. This process involves a fine interplay between the excitatory and inhibitory neurons and synapses and any modulation that affects neuronal activity will modulate the transfer of neuronal information.In addition to nerve cells, the other main cellular elements in the brain are glial cells, in particular one type of glial cells known as astrocytes owing to their stellar shape. These glial cells have long been known as the support cells of the brain, providing nutrients and energy to the nerve cells, while keeping the proper environment for the nerve cells functions. However, a number of studies, including ours, have revealed that glial cells too, are excitable, as they detect and understand neuronal communication. Importantly, as a result of this change in their activity, glial cells modify neuronal excitability and the learning process. Hence, glial cells influence directly the quality of neuronal communication and the propensity of nerve cells to learn and form memory.However, this crucial role of glial cells has been unraveled only for excitatory neurons and their communication, and the impact on the very important inhibitory neuronal network has never been addressed. Hence, the goal of this work is to determine the mechanisms by which glial cells influence inhibitory neurons and how this regulation alters the function of the network of nerve cells and its ability to create learning events.As a whole, this work would allow us to unravel for the first time the ability of glial cells to integrate complex network of neurons. It is becoming clear that a full understanding of the brain and the diseases that affects its functions will never be understood unless the complex interactions between excitatory, inhibitory and glial cells are considered.