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XIth Cajal Conference: New frontiers in neuron‐glial plasticity in health and disease

Alice Louail,I. Bengoetxea de Tena,Rocío Rojas,N. Casals

Published 2023 in European Journal of Neuroscience

ABSTRACT

The brain is a complex assembly of interconnected neurons where synapses enable the transmission of information. Synapses are progressively established in the brain via mechanisms of neuronal competition, where the neurons that fire together, wire together (Hebb, 1949). In other words, the most efficient synapses are strengthened and maintained throughout life, enabling the brain to have a plastic response to the ever-changing environment. This process, globally known as synaptic plasticity, was thought to involve exclusively pre-synaptic and postsynaptic neurons, through the fine regulation of calcium channels and neurotransmitter receptors, among others. Indeed, the classical view of the synaptic connection is an electrical signal leading to the release of a neurotransmitter from the pre-synaptic neuron, which then binds on receptors in the post-synaptic neuron, ultimately inducing a behavioural response. Obviously, complex learning and memory processes in the mammalian brain are more elaborate than this simplistic view and are rooted in a precise regulation of molecular and cellular players. In the last couple of decades, the concept of plasticity has been expanded, as new evidence has uncovered that, besides neurons, glial cells also take a fundamental role in synapse development, homeostasis and plasticity throughout life. Today, astrocytes, microglia and oligodendrocytes and their precursors are considered essential elements for the regulation of synaptic functions and their malleability. In the XIXth century, the Spanish neuroanatomist Santiago Ram on y Cajal already suggested that learning may be mediated by strengthening synapses to improve the efficiency of communication. The classical perception of modulating brain connectivity is long-term potentiation (LTP), a lasting increase in synaptic strength following high-frequency stimulation of a synapse (Lømo, 2003); and its counterpart long-term depression (LTD). Our increasing understanding of plasticity mechanisms has shed light on crucial activity-dependent synaptic regulation and the active role of glial cells, providing a more holistic conception of how the brain functions. The miscellaneous plasticity mechanisms of the brain are in fact guided by the almost infinite possibilities to fine-tune the efficacy of information transmission. Spatial and temporal readjustments include mechanisms affecting the different cell types present, stabilization or destabilization processes, release and receptors binding of neurotransmitters and modulation of the electrical signal, among others. Impairments in the formation, remodelling, strengthening and pruning of synapses underlie most neurodevelopmental and neurological disorders. A better comprehension of these mechanisms would be a stepping-stone to develop pharmacological treatments for pathologies that are fatal nowadays, including Alzheimer’s disease.

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