A Cross-Species Analysis Reveals a General Role for Piezo2 in Mechanosensory Specialization of Trigeminal Ganglia from Tactile Specialist Birds

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Understanding Brains: Details,Intuition, and Big Data

Understanding how the brain works requires a delicate balance between the appreciation of the importance of a multitude of biological details and the ability to see beyond those details to general principles. As technological innovations vastly increase the amount of data we collect, the importance of intuition into how to analyze and treat these data may, paradoxically, become more important.

This Essay is part of the "Where Next?" Series.

Experimental biologists collect details. In the early days, naturalists prowled their backyards, local forests, and meadows. They traveled the Amazon River and African savannahs and collected species and categorized them. These collectors of beetles and ferns then tried to formulate hypotheses about evolutionary relationships by looking at commonalities of structure, function, and development. In those days, there was an implicit belief that the passionate acquisition of detailed information about the idiosyncrasies of individual species contained the route to understanding the general principles of life. Although today’s experimental neuroscientists employ much more sophisticated methods, most retain a deep conviction that the specific properties of molecules, synapses, neurons, circuits, and connectomes are important for understanding how brains, be they small or large, work.Modern neuroscience traces much of its history to prescient physiologists, pharmacologists, and anatomists. Early anatomists such as Ramón y Cajal pioneered the use of stains to reveal the structure of neurons and to make astonishing leaps of intuition about the structure and function of brain circuits [1]. Early physiologists and pharmacologists deduced the existence of receptors and kinetics from bioassays [2,3]. Observation and reasoning from first principles led T. Graham Brown [4,5] to first articulate that reciprocal inhibition in the spinal cord could underlie the generation of rhythmic movements. Cajal and Brown anticipated systems neuroscience as we know it today: understanding how the particular properties of neurons and their connections give rise to the complex and adaptive responses that allow animals to interact with each other and their worlds.     

Ultrafast heme-residue bond formation in six-coordinate heme proteins: implications for functional ligand exchange

A survey is presented of picosecond kinetics of heme-residue bond formation after photolysis of histidine, methionine, or cysteine, in a broad range of ferrous six-coordinate heme proteins. These include human neuroglobin, a bacterial heme-binding superoxide dismutase (SOD), plant cytochrome b 559, the insect nuclear receptor E75, horse heart cytochrome c and the heme domain of the bacterial sensor protein Dos. We demonstrate that the fastest and dominant phase of binding of amino acid residues to domed heme invariably takes place with a time constant in the narrow range of 5-7 ps. Remarkably, this is also the case in the heme-binding SOD, where the heme is solvent-exposed. We reason that this fast phase corresponds to barrierless formation of the heme-residue bond from a configuration close to the bound state. Only in proteins where functional ligand exchange occurs, additional slower rebinding takes place on the time scale of tens of picoseconds after residue dissociation. We propose that the presence of these slower phases reflects flexibility in the heme environment that allows external ligands (O2, CO, NO, . . .) to functionally replace the internal residue after thermal dissociation of the heme-residue bond.     

Spike initiation and propagation on axons with slow inward currents

We investigate spike initiation and propagation in a model axon that has a slow regenerative conductance as well as the usual Hodgkin-Huxley type sodium and potassium conductances. We study the role of slow conductance in producing repetitive firing, compute the dispersion relation for an axon with an additional slow conductance, and show that under appropriate conditions such an axon can produce a traveling zone of secondary spike initiation. This study illustrates some of the complex dynamics shown by excitable membranes with fast and slow conductances.