Biomedical Engineering Reference
In-Depth Information
Chapter 9
Complexity and Computation at the Synapse:
Multilayer Architecture and Role
of Diffusion in Shaping Synaptic Activity
and Computation
Andrea Barberis and Fabio Benfenati
The nervous system confers living organisms the ability to perceive and appro-
priately 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 diverse 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 appro-
priate 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” structures where
presynaptic stimuli are linearly converted into neurotransmitter release and action
potentials. This idea has now been replaced by a more modern view, whereby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.
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