Complexity and computation at the synapse: Multilayer architecture and role of diffusion in shaping synaptic activity and computation

Abstract

The nervous system confers living organisms the ability to perceive and appropriately respond to external signals. At any given moment, a multitude of different stimuli are received, processed, and integrated by the brain. The correct handling of this huge amount of information requires the coordination of extraordinary number of different events at both cellular and network levels. The basis of this extremely complex regulation lays on synapses, the specific contact sites between neurons. At the presynaptic level, electrical stimuli are translated into chemical signals, i.e., the release of neurotransmitters, which are recognized and translated into an appropriate biological response (either electric or metabolic, or both) at the postsynaptic level. The combined action of synapses acting in distinct brain areas is ultimately responsible for the generation and shaping of higher brain functions such as learning and memory. The molecular mechanisms modulating synaptic function have been the subject of intense investigation since the earliest days of modern neuroscience. Initially, synapses were thought to be “static” Structers Where presynaptic stimuli are linearly converted into neurotransmitter release and action potentials. This idea has been now substituted by a more modern view, whereby synapses represent extremely dynamic sites whose activity can be modified by a vast array of signals coming from the presynaptic, postsynaptic, and extracellular compartments as well as by the previous history of the neuron. This new view of synaptic functioning has been obtained by the application of novel advanced techniques that allow interrogating the synapses in live neurons under various environmental conditions, among these are patch-clamp electrophysiology, dynamic electron microscopy, and innovative imaging and optogenetic techniques coupled with high-resolution and super-resolution live imaging approaches.