The History of the Synapse

Sotelo, Constantino

doi:10.1002/ar.24392

Cited by 18 publications

(15 citation statements)

References 150 publications

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“…Electrochemical transmission is the canonical mode of information processing by the nervous system (148,149). The evidence in this review demonstrates the feasibility of combining targeted and untargeted metabolomics to identify candidate molecules that modulate visceral functions of the prefrontal cortex.…”

Section: Conclusion Tensions and Future Directionsmentioning

confidence: 90%

Prefrontal Cortex Metabolome Is Modified by Opioids, Anesthesia, and Sleep

Lydic

Baghdoyan

2021

Physiology

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Obtundation of wakefulness caused by opioids and loss of wakefulness caused by anesthetics and sleep significantly alter concentrations of molecules comprising the prefrontal cortex (PFC) metabolome. Quantifying state-selective changes in the PFC metabolome is essential for advancing functional metabolomics. Diverse functions of the PFC suggest the PFC metabolome as a potential therapeutic entry point for countermeasures to state-selective autonomic dysfunction.

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Section: Conclusion Tensions and Future Directionsmentioning

confidence: 90%

Prefrontal Cortex Metabolome Is Modified by Opioids, Anesthesia, and Sleep

Lydic

Baghdoyan

2021

Physiology

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“…Microscopy confirmed his first observations, and Leeuwenhoek (1695) showed that the nerves coming out of the brain were assembled in hollow fibrils [ 95 ]. However, it was only two centuries later that Cajal provided the basis for modern neuroscience, and Sherington would bring us into modern neurobiology, naming “synapse” what Cajal had previously identified as “nerve joint” [ 96 ].…”

Section: The Psychic Life Of Microorganismsmentioning

confidence: 99%

“…This allowed understanding the general principles of their organisations, from the simplest to the most complex ones. Importantly, Cajal hypothesised the existence of a relationship between the architecture of neural networks and their functionalities, a working basis that will remain until today at the heart of the reflection in attempts to elucidate the functioning of nervous systems [ 96 ]. In addition, Cajal’s artistic sense, the quality of his representations and his wonder brought conceptual and technical rigour to science but also blurred the boundaries between science and the arts [ 102 ].…”

Section: The Psychic Life Of Microorganismsmentioning

confidence: 99%

Towards the Idea of Molecular Brains

Timsit

Sergeant-Perthuis

2021

IJMS

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How can single cells without nervous systems perform complex behaviours such as habituation, associative learning and decision making, which are considered the hallmark of animals with a brain? Are there molecular systems that underlie cognitive properties equivalent to those of the brain? This review follows the development of the idea of molecular brains from Darwin’s “root brain hypothesis”, through bacterial chemotaxis, to the recent discovery of neuron-like r-protein networks in the ribosome. By combining a structural biology view with a Bayesian brain approach, this review explores the evolutionary labyrinth of information processing systems across scales. Ribosomal protein networks open a window into what were probably the earliest signalling systems to emerge before the radiation of the three kingdoms. While ribosomal networks are characterised by long-lasting interactions between their protein nodes, cell signalling networks are essentially based on transient interactions. As a corollary, while signals propagated in persistent networks may be ephemeral, networks whose interactions are transient constrain signals diffusing into the cytoplasm to be durable in time, such as post-translational modifications of proteins or second messenger synthesis. The duration and nature of the signals, in turn, implies different mechanisms for the integration of multiple signals and decision making. Evolution then reinvented networks with persistent interactions with the development of nervous systems in metazoans. Ribosomal protein networks and simple nervous systems display architectural and functional analogies whose comparison could suggest scale invariance in information processing. At the molecular level, the significant complexification of eukaryotic ribosomal protein networks is associated with a burst in the acquisition of new conserved aromatic amino acids. Knowing that aromatic residues play a critical role in allosteric receptors and channels, this observation suggests a general role of π systems and their interactions with charged amino acids in multiple signal integration and information processing. We think that these findings may provide the molecular basis for designing future computers with organic processors.

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“…When sir Sherrington introduced the term 'synapsis' [1], it was still unknown whether or not nerve impulses reach their target through direct electrical coupling [2,3]. Together with other evidence, it was the visualization by electron microscopy of the synaptic cleft, the narrow gap between an axon and its target, which put the debate to rest in favor of transmitter-mediated neurotransmission [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse

Sierksma

Borst

2021

Preprint

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At synapses, the pre- and postsynaptic cell get so close that currents entering the cleft do not flow exclusively along its conductance, gcl. A prominent example is found in the calyx of Held synapse in the medial nucleus of the trapezoid body, where the presynaptic action potential can be recorded in the postsynaptic cell in the form of a prespike. Here, we developed a theoretical framework for ephaptic coupling via the synaptic cleft. We found that the capacitive component of the prespike recorded in voltage clamp is closely approximated by the second time derivative of the presynaptic action potential. Its size scales with the fourth power of the radius of the synapse, explaining why intracellularly recorded prespikes are uncommon in the CNS. We show that presynaptic calcium currents can contribute to the prespike and that their contribution is closely approximated by the scaled first derivative of these currents. We confirmed these predictions in juvenile rat brainstem slices, and used the presynaptic calcium currents to obtain an estimate for gcl of ~1 μS. We demonstrate that for a typical synapse geometry, gcl is scale-invariant and only defined by extracellular resistivity, which was ~75 Ωcm, and by cleft height. During development the calyx of Held develops fenestrations. These fenestrations effectively minimize the cleft potentials generated by the adult action potential, which would otherwise interfere with calcium channel opening. We thus provide a quantitative account of the dissipation of currents by the synaptic cleft, which can be readily extrapolated to conventional, bouton-like synapses.

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The History of the Synapse

Cited by 18 publications

References 150 publications

Prefrontal Cortex Metabolome Is Modified by Opioids, Anesthesia, and Sleep

Prefrontal Cortex Metabolome Is Modified by Opioids, Anesthesia, and Sleep

Towards the Idea of Molecular Brains

Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse

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