The bulk of brain energy expenditure is allocated for maintenance of perpetual intrinsic activity of neurons and neural circuits. Long-term electrophysiological and neuroimaging studies in anesthetized and behaving animals show, however, that the great majority of nerve cells in the intact brain do not fire action potentials, i.e., are permanently silent. Herein, I review emerging data suggesting massive redundancy of nerve cells in mammalian nervous system, maintained in inhibited state at high energetic costs. Acquired in the course of evolution, these collections of dormant neurons and circuits evade routine functional undertakings, and hence, keep out of the reach of natural selection. Under penetrating stress and disease, however, they occasionally switch in active state and drive a variety of neuro-psychiatric symptoms and behavioral abnormalities. The increasing evidence for widespread occurrence of silent neurons warrants careful revision of functional models of the brain and entails unforeseen reserves for rehabilitation and plasticity.

Faculty of Medicine at Charles University 116 36 Prague Czech Republic

Institute for Biological and Medical Imaging Helmholtz Zentrum Munich Neuherberg Germany

International Centre for Neurotherapeutics Dublin City University Dublin Republic of Ireland

Munich School of Bioengineering Technical University Munich Munich Germany

National Institute of Mental Health Topolová 748 250 67 Klecany Czech Republic

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Visualizing cortical response to optogenetic stimulation and sensory inputs using multispectral handheld optoacoustic imaging