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This chapter discusses the ecology of open oceans in polar regions. Topics covered include gradients in waters, the plankton, the physiological ecology of polar phytoplankton, the zooplankton, squid, fish, and polar marine pelagic systems.

The rapid conduction of signals by neurons over distances greater than about 1 mm occurs almost exclusively by electrical impulses. This chapter presents the fundamental concepts that underlie the generation and propagation of these nerve impulses. After a brief historical summary, the remainder of the chapter describes the voltage-clamp experiments of A. L. Hodgkin and A. F. Huxley on the giant axon of the squid. The results and the conclusions furnished by these seminal experiments provide the bases for the current understanding of the electrical nature of neuronal signaling. The Hodgkin-Huxley experiments, together with the equations that encapsulate the experimental results, are presented here in detail to emphasize their central importance for neurophysiology and to present an exemplar of science at its best.

This chapter discusses the cytoskeleton of the squid giant axon. The squid giant axon has given invaluable information about the axonal cytoskeleton and has, for decades, provided an unparalleled model for studies on the cytoskeleton. A major feature of the preparations is that the cytoplasm of the axon can be easily removed from the surrounding membrane, and thus pure neuronal axoplasm can be studied, free of contamination from the axolemma and from other cell types. Hundreds of milligrams of axoplasm can be quickly extracted from a single axon, providing enough material in a near native state for conventional biochemistry. It is not surprising, therefore, that studies on the squid giant axon have been pivotal in understanding the structure and function of neurofilaments and microtubules, major elements of this cytoskeleton. The most abundant cytoskeletal component in squid axoplasm is the neurofilament. The neurofilament polypeptides constitute about 13 per cent of the total axoplasmic protein, and most of these molecules (95 per cent) are polymerized into stable structures that do not readily exchange subunits with the environment. The polypeptide structure has been analysed, and the filaments shown to belong to the family of intermediate filaments. They are altered by two post-translational events: proteolysis and phosphorylation. Progress on cloning squid neurofilament genes is described.

John Moore initially became known for elucidating the action of tetrodotoxin and other neurotoxins using his innovative sucrose gap method for voltage clamping squid axon. He also was a pioneer in the nascent area of computational neuroscience, using computer simulations in parallel with experiments to predict experimental results and thus validate the concepts used in modeling. Intrigued by the possibility of applying his knowledge of physics to learn how neurons employ electricity to generate and transmit signals, he led the field in exploring how ion channels and neuronal morphology affect excitation and signal propagation. He developed electronic instrumentation of high precision for electrophysiology, the result of experience gained through an unconventional career path: early training in physics, assignments involving feedback in the Manhattan Project, and learning principles of operational amplifiers at the RCA Laboratories. His summers at the Marine Biological Laboratory in Woods Hole, MA, now exceeding 50, made much of his work possible and established the MBL as his intellectual home. In retirement, he developed the educational software Neurons In Action, coauthored with his wife Ann Stuart, that is now widely used as a learning tool in neurophysiology.

Gasser takes up the Directorship of the Rockefeller Institute for Medical Research and appoints the Spaniard, Lorente de Nó, as one of his staff. Lorente, who trained in histology under Cajal, begins a long and painstaking physiological investigation of frog sciatic nerve. At the same time, at Columbia University, Kenneth Cole and Howard Curtis examine impedance changes in the membrane of the squid giant axon, a preparation recently discovered by J. Z. Young. Working in the summer at Woods Hole, Cole and Curtis are able to demonstrate that the impulse is associated with a dramatic fall in the electric impedance of the squid axon membrane.

Influenced partly by William Rushton, Alan Hodgkin, a young Trinity College Fellow, has already demonstrated that there are excitability changes in the nerve membrane even when the impulse is blocked. After spending some time with Cole and Curtis in Woods Hole, Hodgkin decides to do some experiments of his own on the squid giant axon and engages Andrew Huxley, who has just finished his undergraduate studies, to help him. The two are able to insert a glass microelectrode down the interior of a giant axon and, for the first time, to record the potential across the nerve fibre membrane directly. They find that the potential reverses during the passage of the nerve impulse, the inside of the fibre becoming briefly positive with respect to the outside.

Hodgkin and Huxley publish the full version of their pre-war findings in the squid giant axon. Unaware of an important paper by Overton, they neglect to include an increase in sodium permeability as a possible cause of the brief reversal of membrane polarity during the impulse. In 1947, however, Hodgkin sets out to explore the effect of sodium ion concentration on the nerve impulse, this time with Katz as a colleague. They find that the rate of rise and the amplitude of the action potential (impulse) increase with the sodium ion concentration. Their results suggest that the reversal of membrane polarity during the action potential is due to a transient increase in sodium permeability. Meanwhile Lorente de Nó publishes his monolithic study of excitability in frog nerve. Unaware of the nerve sheath acting as a diffusion barrier, he wrongly concludes that potassium and sodium ions have minor roles in the genesis of the resting and action potentials.

Now in Chicago, Kenneth Cole employs a negative feedback circuit, devised by a colleague, to clamp the voltage across the membrane of the squid giant axon. He shows that during the action potential there is an initial inward current followed by an outward current, and he attributes the latter to potassium ions. Hodgkin visits Cole who shows him the new technique and loans him some of the apparatus needed for voltage-clamp work. Within a few months Hodgkin has his own voltage-clamp system built and resumes work with Huxley on the squid giant axon at Plymouth, initially with Katz as well. By replacing sodium in the bathing fluid with choline, they are able to show that the early inward current during the action potential is indeed a sodium one, and that the later, outward, current is carried by potassium ions. On the basis of the experimental data Huxley is able to derive an equation describing the flow of current through the nerve membrane at any instant. He and Hodgkin introduce special terms which they interpret as the effects of mobile particles within the membrane. From their equations, Huxley is able to compute the form and conduction velocity of the action potential. The British voltage-clamp work is published in five papers and creates a stir; however, Cole’s assistance is not acknowledged. Hodgkin and Huxley share the 1963 Nobel Prize with Eccles.

This chapter explores the career of neuroscientist Francis O. Schmitt (1903-1995): how his experimental research relied on marine organisms and marine laboratories, and more generally how this earlier phase in his career related to his foundation of the Neurosciences Research Program at MIT from 1962 to 1963. From the 1930s through the 1950s, a network of marine stations, especially the Marine Biological Laboratory in Woods Hole, MA, offered brick-and-mortar places where Schmitt and his colleagues could adopt new experimental systems for studying action potentials. Working from these labs, Schmitt and his colleagues could obtain their choice experimental organisms, squid, which in turn supplied the materials necessary for their work: the abnormally large axons of squid neurons. More theoretically, Schmitt’s research with squid required and facilitated comparative studies, expanding physiologists’ understandings of the varieties of neurons existing in the natural world. Placed into historical context, moreover, Schmitt’s story demonstrates how other neurophysiologists of his era approached such diversity differently than he did, and how finding unifying principles, including amongst the multiplicity of neurons in marine organisms, has always challenged neurobiologists.

In the late 1970s Nina Strömgren Allen and Robert Day Allen, working at the Marine Biological Laboratory (MBL) in Woods Hole, discovered a type of video microscopy that enabled them to visually detect objects in living cells that were below the resolution limit of conventional microscopes. In 1981, collaborating with Scott Brady and Ray Lasek, Robert Allen used his microscopic technique, AVEC-DIC, to look at vesicles moving on filaments in intact axons and extruded axoplasm from the squid giant axon. In 1983, newly-arrived investigators at the MBL, Ron Vale and Mike Scheetz, joined the project, but were soon competing with Allen and Brady in the search for the molecular motor driving transport. In the end, Vale and Scheetz succeeded with the help of Bruce Schnapp and Tom Reese, other MBL scientists, and a key discovery by Brady that facilitated isolation of the motor. Vale named the motor kinesin and demonstrated how it unidirectionally moved vesicles along microtubules. In this story, microscopic observations of a biological process, the transport of vesicles along microtubules, were essential to the discovery and isolation of kinesin, and also insured that the discovery was biologically meaningful by linking biochemical and molecular events directly to biological functions.

This chapter describes the construction of a superconducting artificial atom with two internal degrees of freedom by adding a large inductance to a dc-SQUID phase qubit loop, thus decoupling the junctions’ dynamics.

This chapter presents the basic phenomena and concepts of high-T_c superconductivity. The discovery of Bednorz and Muller, families of cuprate superconductors, and their relation to copper oxide planes are described; along with the Zhang Rice singlet model. Phase diagrams of cuprate and iron based superconductors are shown. The structures of Bi2212 and YBCO are described, emphasizing their layered nature and evidence of a d-wave order parameter. Disorder sites are discussed, and the question of inherent inhomogeneity is addressed in connection with specific heat data. The key experimental features of nodal superconductivity are listed, including the corner SQUID measurement of Van Harlingen and the scanning SQUID images of Tsuei et al. Andreev St. James tunnelling spectra are described.

Barrier tunnelling devices based on the Josephson effect include superconducting quantum interference detectors (SQUID) in conventional and scanning forms. The use of a scanning SQUID detector to detect a half-flux quantum in a ring of Josephson junctions identifies d-wave superconductivity. The shunted Josephson junction is the basis for the rapid single flux quantum RSFQ class of superconducting logic circuits. The use of RSFQ to form fast analogue to digital ADC converter devices is reported. Various types of radiation detectors are described including SIS detectors, Josephson-effect detectors, and optical point-contact antenna devices.

The use of the squid axon as a model system for the study of anaesthetic mechanisms is described. Effects are divided into actions on the voltage-gated Na and K channels and actions on a voltage-independent K conductance system of the nerve membrane. Inhibition of axonal function by anaesthetics arises largely from effects on the Na channel. The precise nature of these effects varies with the physico-chemical properties of the anaesthetic considered, but certain general principles emerge. Small non-polar anaesthetics tend to increase the resting fraction of Na channels in the inactivated state. The actions of certain fluorinated anaesthetics and convulsants on the squid axon are described in the context of the close relationship between anaesthetic and convulsant actions. At low concentrations these molecules all appear capable of increasing axonal excitability and reducing the threshold for action potential generation. This action is related to the inhibition of a resting K permeability system in the axon membrane. The anaesthetics and convulsants can be distinguished in this axonal model on the basis of their relative potencies for inhibition of resting K permeability and Na channels. Convulsants appear to be characterized by an ability to inhibit the resting K permeability, but are inactive, even at high concentrations, on the Na channel. It is suggested that these properties may parallel the wider biological actions of anaesthetics and convulsants including actions on the central nervous system.

This chapter summarizes the progress in developing a model system for studying the control of neuronal Na channel distribution based on the squid giant axon and its cell bodies located in the giant fibre lobe (GFL) of the stellate ganglion. Patch clamp methods have been employed to test the functional integrity of Na channels in GFL neurones maintained in primary culture, and to map the spatial distribution in cell bodies and axons. GFL neurones in vitro establish and maintain a strongly polarized Na channel distribution similar to that displayed by the system in vivo. Several manipulations that disrupt this cellular polarity, including a novel effect of the glycosylation inhibitor tunicamycin, have been identified. This drug appears to selectively inhibit high-level expression of Na channels in axonal membrane. Specificity of neuronal function at the cellular level is largely dictated by the precise spatial distribution of membrane receptors and channels. In general, the functional properties of many channels and receptors have been well studied, and in some cases their spatial distributions have been carefully mapped. Although this information is vital to understanding nerve cell function, there is still a need to learn much more about the cell biological dynamics that control both the properties and the spatial distributions of these important membrane proteins. All neurones are functionally and morphologically polarized, and the number of cellular control elements is large.

Schwann cells are the class of glial cells of the peripheral nervous system associated with axons. The myelin-forming Schwann cells of large-diameter vertebrate axons have a clear physiological function important for axonal physiology. The squid giant axon shows a complex system for chemical signalling from axon to Schwann cell, which may be an important way for the Schwann cells to match their activity to the requirements of the axon. As the signalling involves modulation of the electrophysiological properties of the Schwann cell, a complete understanding of the signalling requires consideration of these electrical properties. The electrophysiological properties also determine the mechanisms available for ionic homeostasis of the periaxonal microenvironment. This chapter reviews current understanding of the resting and activated properties of the Schwann cell membrane, and the implications for signalling and ionic homeostasis. This survey of studies on the electrophysiology of squid Schwann cells shows a general consistency between observations in Sepioteuthis, Alloteuthis, and Loligo, good evidence for the generality of the phenomena. The documented membrane properties of the Schwann cells make for efficient periaxonal ion regulation. Further characterization of the membrane ion channels responsible for the resting and activated electrical behavior of the membranes requires rigorous study using the patch-clamp technique.

Synaptic transmission in the squid stellate ganglion is studied in this chapter. The giant synapse is the last junction in a three-link chain of giant neurons that form the escape system in squid. This chain is a bilaterally symmetrical system that originates with the first-order giant neurons located one on each side of the ventral magnocellular lobe of the brain. Each of the two first-order neurons sends its axon toward the midline, where it fuses with its counterpart to form a cytoplasmic bridge. After forming this bridge the two axons course caudally to make axo-axonic synapses with the second-order giant cells in the dorsal magnocellular lobe. The axons of the second-order neurones in turn leave the brain in the palliai nerves and terminate in the stellate ganglia. In each stellate ganglion, the axon of the second-order generates eight to 10 presynaptic terminal digits. Each of these terminals contacts a third-order axon, the last link in the chain. The giant synapses are axo-axonic junctions between the axon of the second-order giant neurone in the brain and the giant axons of the stellate ganglion. Presynaptic membrane depolarization (release coupling at chemical junctions), the most common triggering signal for release, is achieved by an influx of calcium into the presynaptic terminal. A synaptic transmitter is released from specialized sites characterized by the confluence of an intracellular calcium concentration increase, the biochemical cascade triggered by the calcium, and the intracellular organelles involved in this secretory event.

This chapter considers the recent studies that use the fluorescent Ca²⁺ indicator, fura-2, to further characterize presynaptic Ca²⁺ signaling. The fluorescent Ca indicator, fura-2, can be used to measure the changes in presynaptic Ca concentration associated with action potentials. When using either a photomultiplier tube or a video camera to detect fura-2 fluorescence, trains of presynaptic action potentials produce rapid rises in Ca concentration that reach a peak level of a few nM per action potential and which decay very slowly, over hundreds of seconds. However, these measured rises are not those responsible for triggering transmitter release because injection of the Ca buffer, EGTA, blocks them in Ca concentration but not transmitter release. EGTA injection blocks synaptic augmentation, a form of synaptic plasticity which increases the amount of release produced by an action potential, suggesting that the measured Ca rises mediate augmentation. The Ca²⁺ signal for neurotransmitter release must be localized to escape detection in imaging experiments. Other experiments suggest that this localization occurs as a consequence of a close spatial association between Ca²⁺ channels and the Ca²⁺ receptors which trigger release. The chapter concludes with the observation that the transmitter release is mediated by a rise in Ca concentration which is too localized to be detected with fura-2 measurements, while augmentation is mediated by a more widespread and detectable Ca signal.