Marco Piccolino

The bicentennial of the Voltaic battery (1800-2000) : the artificial electric organ

Alessandro Volta invented the electric battery at the end of 1799 and communicated his invention to the Royal Society of London in 1800. The studies that led him to develop this revolutionary device began in 1792, after Volta read the work of Luigi Galvani on the existence of an intrinsic electricity in living organisms. During these studies, Volta obtained a series of results of great physiological relevance, which led him to anticipate some important ideas that marked the inception of modern neuroscience. These results have been obscured by a cultural tradition that has seen Volta exclusively as a physicist, lacking interest for biological problems and opposed in an irreversible way to the physiologist, Luigi Galvani.

Calcium-independent synaptic transmission: artifact or fact?

The release of neurotransmitters at classical chemical synapses occurs via Ca2+ influx through voltage-dependent Ca2+ channels, which are opened following depolarization of presynaptic terminals. However, owing to a persistence or increase in the amount of transmitter released in preparations containing low concentrations of Ca2+, it has been proposed that transmitter release could also occur through a Ca(2+)-independent, carrier-mediated process. On the other hand, lowering extracellular [Ca2+] can actually promote Ca2+ influx through voltage-activated Ca2+ channels via a modification of the surface potential of plasma membranes. Therefore, the proposed Ca(2+)-independent transmitter release could be re-accommodated within the framework of the Ca2+ hypothesis of synaptic transmission by taking into account the surface-charge effects.

Involvement of D1 and D2 Dopamine Receptors in the Control of Horizontal Cell Electrical Coupling in the Turtle Retina

We studied the actions of D1 and D2 dopamine agonists and antagonists on the coupling of horizontal cell axons in the turtle retina by a combinationn of pharmacological and electrophysiological methods. Both D1 and D2 receptors were identified in membrane fractions by radioligand binding using [3H]‐SCH 23390 and [3H]‐spiperone, respectively. The KD of both receptor classes were identical (0.21 nM) but D1 receptor density exceeded that of D2 receptors by more than four‐fold. D1 agonists increased the activity of adenylate cyclase in a dose‐dependent manner, whereas D2 agonists were without significant effect by themselves, nor did D2 antagonists block the D1‐mediated increase in adenylate cyclase activity. Intracellular recordings and Lucifer Yellow dye injections were used to characterize the modifications of the receptive field profile of horizontal cell axons (H1AT) exposed to different pharmacological agents. Dopamine or D1 agonists (0.05–10 μM) induced a marked constriction of the H1AT receptive field, whereas D2 agonists elicited a small expansion of the receptive field. However, in the presence of a D1 antagonist, as well as IBMX to inhibit phosphodiesterase, D2 agonists (10–70 μM) induced a marked increase in the receptive field profile. These results indicate that both D1 and D2 dopamine receptors play a role in shaping the receptive field profile of the horizontal cell axon terminal in the turtle retina.

Galileo's Eye: A New Vision of the Senses in the Work of Galileo Galilei:

Reflections on the senses, and particularly on vision, permeate the writings of Galileo Galilei, one of the main protagonists of the scientific revolution. This aspect of his work has received scant attention by historians, in spite of its importance for his achievements in astronomy, and also for the significance in the innovative scientific methodology he fostered. Galileos vision pursued a different path from the main stream of the then contemporary studies in the field; these were concerned with the dioptrics and anatomy of the eye, as elaborated mainly by Johannes Kepler and Christoph Scheiner. Galileo was more concerned with the phenomenology rather than with the mechanisms of the visual process. His general interest in the senses was psychological and philosophical; it reflected the fallacies and limits of the senses and the ways in which scientific knowledge of the world could be gathered from potentially deceptive appearances. Galileos innovative conception of the relation between the senses and external reality contrasted with the classical tradition dominated by Aristotle; it paved the way for the modern understanding of sensory processing, culminating two centuries later in Johannes Müllers elaboration of the doctrine of specific nerve energies and in Helmholtzs general theory of perception.

CALCIUM-INDEPENDENT RELEASE OF NEUROTRANSMITTER IN THE RETINA : A COPERNICAN VIEWPOINT CHANGE

The release of synaptic transmitter in chemical synapses is brought about by Ca2+ influx through voltage-dependent Ca2+ channels opened by depolarisation of presynaptic terminals. However, in some preparations transmitter release persists or increases in low-Ca2+ media, and it has therefore been proposed that transmitter release could also occur through a Ca2+-independent, carrier mediated process. In particular it has been suggested that this may be the case for synaptic transmission between photoreceptors and second order neurones of the vertebrate retina. From our recent experiments on synaptic transmission from photoreceptors to horizontal cells of turtle and salamander retinas, it appears that lowering extracellular Ca2+ can actually promote Ca2+ influx through voltage-activated Ca2+ channels via a modification of surface potential of plasma membranes. On the basis of this apparently paradoxical effect of low Ca2+ media, it is possible to reaccommodate the so-called Ca2+-independent release within the framework of Ca2+-dependent synaptic transmission without invoking unconventional mechanisms.

Visual images in Luigi Galvani's path to animal electricity.

The scientific endeavor that led Luigi Galvani to his hypothesis of “animal electricity,” i.e., of an electricity present in a condition of disequilibrium between the interior and the exterior of excitable animal fibers, is reviewed here with particular emphasis to the role played by visual images in Galvanis path of discovery. In 1791 Galvani formulated his model of neuromuscular physiology on the base of the image of a muscle and a nerve fiber together as in a “minute animal Leyden jar.” This was the last instance of a series of physical models that accompanied Galvanis experimental efforts in the search of a theory capable of accounting for the electric nature of nerve conduction in spite of the many objections formulated in the eighteenth century against a possible role of electricity in animal physiology.

Alexander von Humboldt: Galvanism, Animal Electricity, and Self-Experimentation Part 2: The Electric Eel, Animal Electricity, and Later Years

After extensive experimentation during the 1790s, Alexander von Humboldt remained skeptical about “animal electricity” (and metallic electricity), writing instead about an ill-defined galvanic force. With his worldview and wishing to learn more, he studied electric eels in South America just as the new century began, again using his body as a scientific instrument in many of his experiments. As had been the case in the past and for many of the same reasons, some of his findings with the electric eel (and soon after, Italian torpedoes) seemed to argue against biological electricity. But he no longer used galvanic terminology when describing his electric fish experiments. The fact that he now wrote about animal electricity rather than a different “galvanic” force owed much to Alessandro Volta, who had come forth with his “pile” (battery) for multipling the physical and perceptable effects of otherwise weak electricity in 1800, while Humboldt was deep in South America. Humboldt probably read about and saw voltaic batteries in the United States in 1804, but the time he spent with Volta in 1805 was probably more significant in his conversion from a galvanic to an electrical framework for understanding nerve and muscle physiology. Although he did not continue his animal electricity research program after this time, Humboldt retained his worldview of a unified nature and continued to believe in intrinsic animal electricity. He also served as a patron to some of the most important figures in the new field of electrophysiology (e.g., Hermann Helmholtz and Emil du Bois-Reymond), helping to take the research that he had participated in to the next level.

Galileo Galilei’s vision of the senses

Neuroscientists have become increasingly aware of the complexities and subtleties of sensory processing. This applies particularly to the complex elaborations of nerve signals that occur in the sensory circuits, sometimes at the very initial stages of sensory pathways. Sensory processing is now known to be very different from a simple neural copy of the physical signal present in the external world, and this accounts for the intricacy of neural organization that puzzled great investigators of neuroanatomy such as Santiago Ramón Y Cajal a century ago. It will surprise present-day sensory neuroscientists, applying their many modern methods, that the conceptual basis of the contemporary approach to sensory function had been recognized four centuries ago by Galileo Galilei.

Santiago Ramón Y Cajal, the retina and the neuron theory

‘A small block of nervous tissue left from several days, hardening in Muller fluid alone or mixed with osmic acid. Because the histologist was distracted, or because of a scientist’s curiosity, it was immersed in a bath of silver nitrate. One sections the block, dehydrates the sections, clears them, and examines them. Surprising sight! Against a perfectly translucent, yellow background, appear, thinly dispersed, the black filaments, either smooth and delicate or spiny and thick; the black cell bodies, triangular, stellate, fusiform. They might be drawings done with India ink on transparent Japanese vellum. One is taken aback; the eye is accustomed to the inextricable tangles seen in sections stained with carmine or hematoxylin, where the mind strains in prodigies of criticism and interpretation, always in doubt. Here everything is simple, clear without confusion. Nothing more to interpret.

Fifty years of the Hodgkin-Huxley era

Modern neuroscientists are accustomed to the detailed information on the structure and function of membrane ion channels that can be obtained by the combination of molecular biology, crystallography and patch-clamp recordings. It can be difficult for us to appreciate how hard it was for humankind to realize that physical events underlie nervous function and, moreover, to appreciate how long it took to devise a realistic model for the generation and propagation of the nerve impulse.