Showing papers in "The Journal of Physiology in 1959"

Receptive fields of single neurones in the cat's striate cortex

Abstract: In the central nervous system the visual pathway from retina to striate cortex provides an opportunity to observe and compare single unit responses at several distinct levels. Patterns of light stimuli most effective in influencing units at one level may no longer be the most effective at the next. From differences in responses at successive stages in the pathway one may hope to gain some understanding of the part each stage plays in visual perception. By shining small spots of light on the light-adapted cat retina Kuffler (1953) showed that ganglion cells have concentric receptive fields, with an 'on' centre and an 'off ' periphery, or vice versa. The 'on' and 'off' areas within a receptive field were found to be mutually antagonistic, and a spot restricted to the centre of the field was more effective than one covering the whole receptive field (Barlow, FitzHugh & Kuffler, 1957). In the freely moving lightadapted cat it was found that the great majority of cortical cells studied gave little or no response to light stimuli covering most of the animal's visual field, whereas small spots shone in a restricted retinal region often evoked brisk responses (Hubel, 1959). A moving spot of light often produced stronger responses than a stationary one, and sometimes a moving spot gave more activation for one direction than for the opposite. The present investigation, made in acute preparations, includes a study of receptive fields of cells in the cat's striate cortex. Receptive fields of the cells considered in this paper were divided into separate excitatory and inhibitory ('on' and 'off') areas. In this respect they resembled retinal ganglion-cell receptive fields. However, the shape and arrangement of excitatory and inhibitory areas differed strikingly from the concentric pattern found in retinal ganglion cells. An attempt was made to correlate responses to moving stimuli

The influence of potassium and chloride ions on the membrane potential of single muscle fibres.

Abstract: The most widely accepted theory of the restirng potential of muscle is that the electrical potential difference between the inside and outside of a muscle fibre arises from the concentration gradients of the potassium and chloride ions. If we follow Boyle & Conway (1941), the membrane is assumed to be permeable to K and Cl but to be impermeable or sparingly permeable to other ions. Since K is more concentrated inside and Cl is more concentrated outside, the interior of the fibre should be electrically negative to the external solution. If K and Cl are distributed passively, the concentration ratios and the membrane potential under equilibrium conditions ought to conform to the relation

The effects of lesions in the hypothalamus in parabiotic rats

Abstract: An adult animal's intake and expenditure of energy are normally almost equal over long periods. This equality is probably brought about mainly by adjustment of the amount of food eaten. Regulation of food intake is particularly efficient in the young adult rat, which can adjust its intake to provide a nearly constant supply of calories when the bulk it must eat is varied by diluting the food with inert material (Adolph, 1947; Kennedy, 1950). In the rat and other mammals which have been investigated, bilateral lesions in the region of the ventromedial nuclei of the hypothalamus cause obesity if the animal has free access to food which it finds palatable; the obesity is due, mainly if not entirely, to an increase in the amount of food eaten (Hetherington & Ranson, 1942; Brobeck, 1946; Kennedy, 1950). It has therefore been suggested that the hypothalamus contains nervous centres which normally control the intake of food, and that these are damaged by the lesions (Anand & Brobeck, 1951). There has been much discussion of the way in which these centres work. It is difficult to see how they can directly measure the number of calories expended in a given period, and then regulate feeding to provide just this amount of energy. Alternatively, the regulk ing centres may be sensitive to some change in the body which follows the intake or expenditure of energy, and they may inhibit or encourage eating until the changed quantity has been restored to normal. This would be a 'feedback' control system: the controlling centres would be acting on information, fed back to them from the periphery, about the behaviour of the quantity they stabilized. Mechanisms of this type are known to be important in the body, as well as in artificial control mechanisms. Brobeck (1948), Mayer (1952) and Kennedy (1953b) have proposed systems of the feedback type in relation to the control of food intake. It has not, however, been directly demonstrated

The recirculation of lymphocytes from blood to lymph in the rat

Abstract: In all the mammalian species which have so far been examined, large numbers of lymphocytes enter the blood each day from the main lymphatic vessels in the neck (reviewed by Yoffey & Courtice, 1956). In the rat, for example, enough lymphocytes enter the blood from the thoracic duct to replace all those in the blood about 11 times daily (Gowans, 1957a). This is a minimum estimate of the actual daily replacement since it ignores the contribution from the lymphatics which drain the head, neck, forelimbs and thorax; taking these into account Whaler & Widdicombe (1956) estimated that the average time spent by lymphocytes in the blood of the rat was probably less than one hour. Many theories have been advanced to explain this rapid turnover of lymphocytes in the blood but none of them has good experimental support (Yoffey & Courtice, 1956; Florey & Gowans, 1958; Trowell, 1958). In a previous paper (Gowans, 1957 a) it was shown that in order to maintain the output of lymphocytes from a thoracic duct fistula in an unanaesthetized rat it was necessary to re-infuse continuously into the blood all the lymphocytes which issued from the fistula. When either cell-free lymph or lymph which contained killed lymphocytes was re-infused a profound fall in the output of cells from the thoracic duct eventually occurred, similar to that described by Mann & Higgins (1950) in rats which received no intravenous replacement of either cells or fluid. The aim of the present investigation was to discover the mechanism by which the intravenous infusion of living lymphocytes influenced the output of lymphocytes from the thoracic duct. Essentially, this aim was achieved by determining the fate of thoracic duct lymphocytes after their transfusion into the blood. Preliminary accounts of these experiments have already been given (Gowans, 1957 b, 1958).

Single unit activity in striate cortex of unrestrained cats.

Abstract: A beginning has recently been made in recording single neurone activity from animals with chronically implanted electrodes (Hubel, 1957a; Gusel'nikov, 1957; Ricci, Doane & Jasper, 1957; Strumwasser, 1958). These methods eliminate anaesthetics, paralysing drugs, brain-stem lesions, and other acute experimental procedures. They make it possible to record electrical events in the higher central nervous system with the animal in a normal state, and to correlate these electrical events with such variables as waking state, attention, learning, and motor activity. The present paper describes a method for unit recording from the cortex of unanaesthetized, unrestrained cats, and presents some observations from the striate cortex. The objectives have been (1) to observe maintained unit activity under various conditions such as sleep and wakefulness, and (2) to find for each unit the natural stimuli which most effectively influence firing. Of 400 units observed, some 200 are presented here because of their common characteristics. Since there is reason to believe that the remainiing 200 units were afferent fibres from the lateral geniculate nucleus, these will be described in a separate paper. A preliminary account of some of this work has been given elsewhere (Hubel, 1958).

The dependence of tension upon extension in the stretch reflex of the soleus muscle of the decerebrate cat.

Abstract: In their description of the stretch reflex, Liddell & Sherrington (1924) stated that 'so long as the stretch increases, the reflex continues to increase'. The importance of this finding for an understanding of posture has long been recognized; but their statement has an additional interest in that it relates the magnitude of a reflex response to the size of the physiological stimulus which elicited it. The present paper describes a more detailed study of this relation between stimulus (muscle extension) and its reflex response (muscle contraction) in the hope that increased knowledge of the response of the reflex arc will contribute to an understanding of its detailed mechanisms. The relation between tension and extension of the stretch reflex has been previously studied by applying a series of extensions of different lengths to the muscle (Koella, Nakao, Evans & Wada, 1956; Granit, 1958). In the present study the stretch reflex has been elicited by extending the muscle at a slow constant velocity, while recording both its tension and the extension applied to it. In addition, the present paper describes some experiments on the effect of extending the soleus muscle upon the tension developed in it on stimulation of its motor nerve. These experiments show that the 'tetanic fusion frequency' of soleus may vary with its length-a finding of importance for any'discussion of the neural control of the stretch reflex.

Fluctuations of accommodation under steady viewing conditions.

Abstract: It is well known that under steady environmental conditions motor systems exhibit residual fluctuations or unrest. The tremor in skeletal muscles has been extensively studied and shows a dominant frequency component of 10 c/s (Schaefer, 1886). The pupil of the eye shows a physiological unrest with a high frequency component of 1F2 c/s (Stark, Campbell & Atwood, 1958). The tremor of the eyeball during steady fixation has been described as having dominant 30-80 c/s components (Ditchburn & Ginsborg, 1953). While investigating the characteristics of the accommodation response of the eye we noticed that the refractive power undergoes small fluctuations and it is the purpose of this paper to describe these. Attempts to account for motor tremor have often led to feedback theory being invoked (Hammond, Merton & Sutton, 1956; Lippold, Redfearn & Vuco, 1957). The implication of the feedback concept in this connexion is that sensory information from, for example, muscle spindles is fed back to the motor control centre in order that a desired tension or length response of the muscle shall be achieved or maintained (Granit, 1955). In the accommodation system the sensory information comes from the retina and here we have the advantage of easy optical access by natural means, enabling us to manipulate independently the sensory information sent back to the controlling nerve centre, a facility not readily available in other motor systems. Quantitative as well as qualitative data about its components and their interaction are necessary before a feedback system can be fully described and quantitative predictions made. In this paper we are reporting measurements that must be integrated into a quantitative description of the accommodation system if it is given in terms of feedback theory.

The release of 5-hydroxytryptamine in relation to pressure exerted on the intestinal mucosa.

Abstract: In a recent investigation (Biilbring & Lin, 1958) it was found that small amounts of 5-hydroxytryptamine (5-HT) were continuously released into the lumen of an isolated loop of intestine. The quantity released was directly related to the height of intraluminal pressure. Experiments carried out to ascertain whether 5-HT was liberated as a result of pressure on the mucosa, or as a result of peristaltic activity which was evoked by raising the pressure, were not entirely conclusive. When peristaltic activity was abolished either by blocking mucosal sensory receptors with procaine, or by blocking intramural ganglia with hexamethonium, the correlation between pressure and 5-HT release was still observed. However, the extent to which 5-HT release was augmented on raising the intraluminal pressure was less. It was therefore concluded that muscular activity contributed to the mechanism releasing 5-HT, probably by causing, during a peristaltic wave, a considerable additional rise in pressure on the mucosa. The present work was carried out in order to investigate further the mechanism of 5-HT release.

Presynaptic failure of neuromuscular propagation in rats

Abstract: In two earlier publications (Krnjevic & Miledi, 1957, 1958b) we have described a kind of failure of neuromuscular propagation observed during repetitive stimulation of rat nerves in vitro and in situ, which we called presynaptic failure because the propagation block prevented nerve impulses from initiating any synaptic action (see also Kostyuk, 1958). Such failures were therefore to be distinguished from various types of synaptic or post-synaptic failures, e.g. those caused by a decrease in the amount of transmitter liberated, by a reduced sensitivity of the end-plate membrane to acetylcholine (ACh), or by an increase in the electrical threshold of the muscle fibre. With an intracellular micro-electrode in the region of the end-plate, presynaptic failures were easily recognized, since unlike the other types of block they showed no local end-plate potentials (e.p.p.'s). In phrenic-diaphragm preparations in which a motor nerve fibre was isolated, presynaptic failure during repetitive stimulation occurred asynchronously in various muscle fibres of the motor unit (Krnjevid & Miledi 1957, 1958 a). This suggested that the conduction block could not have occurred at any point more central than the peripheral branching of the motor axon. The most likely sites for the presynaptic block therefore seemed to be either points of branching, or the narrow region which precedes the terminal expansion of the nerve fibre. The present paper gives a more detailed description of certain aspects of presynaptic failure, and an account of some experiments designed to determine its probable cause. A preliminary communication of some of the results has already been given (Krnjevid & Miledi, 1959).

The permeability of frog muscle fibres to lithium ions.

Abstract: When Overton (1902) studied the excitability of frog muscle in different media, he found that lithium was the only cation which could be substituted for sodium without causing the fibres to become inexcitable. This suggests that in some ways the behaviour of the muscle membrane towards lithium must be similar to its behaviour towards sodium. In other respects, however, the membrane discriminates between sodium and lithium, as is shown by the experiments described in the preceding paper (Keynes & Swan, 1959) on the effect of lithium on the efflux of labelled sodium from frog muscle. The results of this work on the sodium efflux could not be interpreted without knowing more about the rate of movement of lithium ions through the membrane, and this paper is therefore concerned with some measurements of the lithium influx into freshly dissected muscles, and with the rate at which lithium moves outwards from lithium-loaded muscles. Since lithium has no usable radioactive isotopes (the half-life of 8Li is under 1 sec), we were only able to measure the net rate of transfer of lithium into and out of the muscles, using a flame photometer to determine the lithium contents of muscles treated in various ways. But some useful figures were obtained for the resting influx of lithium from a solution similar in its composition, except for the substitution of Li for Na, to normal frog Ringer's solution, and the extent to which lithium can be actively extruded from the interior of the muscle fibre was also studied. Finally, a few observations were made with intracellular micro-electrodes to see whether there was any obvious difference between the action potentials recorded in Na and in Li Ringer's solution.

Initiation of impulses in visual cells of Limulus

Abstract: Some features of the responses recorded from visual cells of Limulus with intracellular electrodes have been described in a previous article (Fuortes, 1958b). Cells producing spikes of more than 40 mV were tentatively identified with eccentric cells. The response of these cells to prolonged illumination was found to consist of a sustained depolarization (generator potential) with superimposed spikes. It was observed that, in steady-state conditions, both amplitude of the generator potential and frequency of firing are approximately linear functions of the logarithm of light intensity, frequency being therefore a linear function of generator potential amplitude. Impulse firing could also be elicited by means of depolarizing currents applied through the impaling micro-electrode and frequency of firing was then found to be a linear function of current intensity. In the present article some properties of responses elicited by illumination will be compared to those of responses evoked by currents and the results of interaction of light and currents will be described. The evidence obtained in this way indicates that membrane resistance decreases during illumination and suggests that a change of membrane permeability may be responsible for production of the generator potential.

Movements of Na and K in single muscle fibres.

Abstract: The aim of the experiments described here was to investigate the movements of labelled sodium and potassium ions through the surface membrane of single muscle fibres, and to determine the effect of activity on these movements. The advantages of using a single fibre are that the surface area can be measured fairly accurately and that radioactive ions have rapid access to the surface. The second point is important because frog muscle fatigues in a few minutes if stimulated at more than about 3 c/s. Activity can be maintained for long periods at low frequencies but the changes in ionic flux are then too small to be measured accurately. For this reason it is desirable to collect or apply tracer over well-defined periods lasting only a few minutes. This condition is difficult to satisfy with whole muscle. Other disadvantages of whole muscle are the variation in fibre diameter within the muscle and the difficulty of distinguishing between extracellular and intracellular sodium ions. Complications may also arise from the presence of muscle spindles, slow fibres and blood vessels. The disadvantages of the single fibre are the low counting rate associated with the small quantity of tracer inside the fibre and the difficulty of isolating fibres which will survive for long periods of time. However, since neither difficulty is insuperable it seemed desirable to attempt a quantitative analysis of ionic movements along lines similar to those followed in investigating giant nerve fibres (Keynes, 1951). The results agree with the observations of Fenn & Cobb (1936) on mammalian muscle in showing that activity is associated with an entry of sodium ions and a somewhat smaller loss of potassium ions. They also show that labelled K+ and Na+ are lost exponentially from single muscle fibres and that the movements of these ions are of the kind expected in a system in which exchange is limited by a single barrier such as the surface membrane.

The oxygen consumption of new‐born and adult mammals. Its dependence on the oxygen tension in the inspired air and on the environmental temperature

Abstract: Infants during birth and shortly afterwards are particularly liable to suffer from hypoxia, and much research has been directed to elucidating the effects of oxygen lack in the new-born. Evidence that moderate hypoxia (15% oxygen) causes a significant reduction in oxygen consumption in human infants was first produced by Cross, Tizard & Trythall (1955, 1958); it was later reported that lambs (Acheson, Dawes & Mott, 1957), and puppies and kittens (Moore, 1956a, b), respond in a similar fashion. It thus appeared that the new-born respond differently from adults, since it was generally accepted that the oxygen consumption of an adult mammal does not fall until death due to hypoxia is imminent (in the region of 6% oxygen). Then, in a review of the physiology of the new-born, McCance & Widdowson (1957) pointed out that adult small mammals behave in the same way as new-born animals, and not in the 'adult' manner. The situation was now confusing, since it was not clear whether it was size or maturity that determined the response to hypoxia. The present experiments were undertaken in order to make a direct comparison between new-born and adult animals of roughly the same size, and to obtain more information about the various types of response to hypoxia. A brief preliminary report of this work has been published (Hill, 1958).

The effect of external sodium concentration on the sodium fluxes in frog skeletal muscle.

Abstract: Ussing (1949) suggested that part of the observed Na efflux in frog muscle might result from a process that he termed 'exchange diffusion', involving a sodium for sodium exchange across the membrane. Thus, if a carrier with a high affinity for Na were confined to the membrane and able to diffuse across it only when it had formed a complex with Na, there would be a continual movement of labelled Na through the membrane without necessarily any simultaneous consumption of energy. If such a mechanism existed, complete removal of Na from the outside of the membrane might be expected to eliminate a substantial fraction of the total efflux of labelled Na, unless the cation substituted for Na+ could also form a complex with the carrier and thus move across the membrane. We therefore investigated the effect on the Na efflux of substituting choline or lithium for the sodium in the external medium, and found that in both cases the efflux was promptly reduced by about half when the sodium in the interfibre fluid was replaced by the foreign cation. This observation clearly warranted further analysis, and the changes in Na efflux were examined for test muscles with altered internal Na concentrations, and at various temperatures. The effect of partial replacement of external Na was also investigated and the resulting changes in Na efflux were compared with the parallel alterations in Na influx. The effect of removing external Na was found to add to that of removing external K, and the relative magnitude of the two effects was studied as a function of the Na content of the muscles. A preliminary report on this work was made at the XX International Physiological Congress (Swan & Keynes, 1956).

Sodium currents in the myelinated nerve fibre of Xenopus laevis investigated with the voltage clamp technique.

Abstract: It has previously been shown (Dodge & Frankenhaeuser, 1958) that the nodal membrane of frog nerve fibres responds to stepwise changes of membrane potential with a flow of current strikingly similar to that which occurs in the squid giant axon (Hodgkin & Huxley, 1952 a, b, c, d; Hodgkin, Huxley & Katz, 1952). A cathodal step is associated with an initial transient current followed by a delayed lasting outward current. The variation of the amplitude of the initial current with membrane potential, the definite potential at which the initial current changes direction, the dependence of this potential on the external sodium ion concentration, and the variation of the nodal action potential with sodium concentration (Huxley & Stampfli, 1951), suggest that the initial current of the nodal membrane is indeed a sodium current, as it is in the squid giant axon (Hodgkin & Huxley, 1952 a). In the present investigation it will be shown that the effect of changing the external sodium ion concentration is quantitatively consistent with the idea that the nodal membrane, when depolarized, undergoes a transient large increase in its sodium permeability, that this permeability depends on the membrane potential, but not on the sodium concentration, and that the initial current is a flow of sodium ions moving passively down the electrochemical gradient for sodium. Further quantitative analysis of the voltage clamp data will be published later.

The depression of spinal neurones by γ-amino-n-butyric acid and β-alanine

Abstract: It is now generally accepted that the processes of synaptic excitation and inhibition within the mammalian nervous system are chemical in nature (cf. Fatt, 1954; Eccles, 1957). It may therefore be expected that the responsible transmitter substances would be present in extracts of neural tissue. Consequently, the presence of y-amino-n-butyric acid (GABA) within such extracts (Bazemore, Elliott & Florey, 1956) together with the finding that GABA appeared to diminish activity within the cerebral cortex (Hayashi & Nagai, 1956; Purpura, Girado & Grundfest, 1957) led to the plausible assumption that GABA had a specific function within the nervous system. In particular it has been postulated that GABA depresses excitatory post-synaptic potentials (Purpura, Girado & Grundfest, 1957, 1958; Iwama & Jasper, 1957). However, investigations upon other preparations including the crayfish stretch receptor (Edwards & Kuffler, 1957), the perfused lobster heart (Enger & Burgen, 1957), the lobster cardiac ganglion (Maynard, 1958) and the isolated mammalian ileum (Hobbiger, 1958) show that GABA has a depressant action upon a wide variety of tissues. The present investigation has been carried out in order to determine the effect of GABA and substances of related structure upon neurones within the spinal cord of the cat. A preliminary report has been published (Curtis & Phillis, 1958).

Voltage—current relations in nerve cell membrane of Onchidium verruculatum

Abstract: The voltage clamp technique, introduced by Hodgkin, Huxley & Katz (1952) was first used to analyse the membrane conductance changes during activity in the squid giant axon (Hodgkin & Huxley, 1952a-d). Tasaki & Bak (1958), and Dodge & Frankenhaeuser (1958), using a similar technique, examined voltage-current relations in the membrane of a myelinated nerve fibre. However, these investigations were all concerned with nerve fibres. Recently we have applied a similar technique to nerve cell bodies in the supramedullary ganglion of a puffer fish (Hagiwara & Saito, 1957, 1959). The present work was planned to elucidate further the properties of the nerve cell body membrane by use of the voltage clamp technique. The relation between the membrane potential and membrane current was analysed under normal conditions, as well as in the presence of urethane and tetraethyl ammonium ions (TEA). In this work we used a marine pulmonate mollusc, Onchidium verruculatum, which has a number of large nerve cells (100-300 in diameter) in its central nervous system.

Changes in the physical properties of the uterine cervix of the rat during pregnancy.

Abstract: During pregnancy changes take place in the walls of the birth canal, making it more distensible and so facilitating the passage of the foetus at parturition. Investigators of this subject have concentrated mainly on the pelvic bones and interosseous ligaments, in particular the symphysis pubis (see Hisaw & Zarrow, 1950; Frieden & Hisaw, 1953); little work has been done on the uterine cervix which is the narrowest part of the birth canal. We have examined changes in the physical properties of the uterine cervix of the rat during pregnancy. The results indicate that these mainly affect the connective tissue framework and consist, first, of an increase in size so that the diameter to which it can be expanded by relatively low forces is increased, and secondly, of a change in the nature of the material which resists mechanical stretching. This material in the non-pregnant animal is only slightly distensible even by strong forces acting for long times. At the end of pregnancy, however, it shows properties of a very viscous material and distends slowly and progressively even under low forces. The change in the physical properties of the cervix does not begin until the 11-12th day of pregnancy and then is progressive; it involves a relative diminution in the amount of smooth muscle present and a fall in the concentration of collagen. Preliminary accounts of some of this work have already been published (Harkness & Harkness, 1956; Harkness, 1957).