Abstract: 1. We have examined the responses of simple cells in the cat's atriate cortex to visual patterns that were designed to reveal the extent to which these cells may be considered to sum light-evoked influences linearly across their receptive fields. We used one-dimensional luminance-modulated bars and grating as stimuli; their orientation was always the same as the preferred orientation of the neurone under study. The stimuli were presented on an oscilloscope screen by a digital computer, which also accumulated neuronal responses and controlled a randomized sequence of stimulus presentations. 2. The majority of simple cells respond to sinusoidal gratings that are moving or whose contrast is modulated in time in a manner consistent with the hypothesis that they have linear spatial summation. Their responses to moving gratings of all spatial frequencies are modulated in synchrony with the passage of the gratings' bars across their receptive fields, and they do not produce unmodulated responses even at the highest spatial frequencies. Many of these cells respond to temporally modulated stationary gratings simply by changing their response amplitude sinusoidally as the spatial phase of the grating the grating is varied. Nonetheless, their behavior appears to indicate linear spatial summation, since we show in an Appendix that the absence of a 'null' phase in a visual neurone need not indicate non-linear spatial summation, and further that a linear neurone lacking a 'null' phase should give responses of the form that we have observed in this type of simple cell. 3. A minority of simple cells appears to have significant non-linearities of spatial summation. These neurones respond to moving gratings of high spatial frequency with a partially or totally unmodulated elevation of firing rate. They have no 'null' phases when tested with stationary gratings, and reveal their non-linearity by giving responses to gratings of some spatial phases that are composed partly or wholly of even harmonics of the stimulus frequency ('on-off' responses). 4. We compared simple receptive fields with their sensitivity to sinusoidal gratings of different spatial frequencies. Qualitatively, the most sensitive subregions of simple cells' receptive fields are roughly the same width as the individual bars of the gratings to which they are most sensitive. Quantitatively, their receptive field profiles measured with thin stationary lines, agree well with predicted profiles derived by Fourier synthesis of their spatial frequency tuning curves.

Abstract: 1. Single channel currents through acetylcholine receptor channels (ACh channels) were recorded at chronically denervated frog muscle extrajunctional membranes in the absence and presence of the lidocaine derivatives QX-222 and QX-314. 2. The current wave forms due to the opening and closing of single ACh channels (activated by suberyldicholine) normally are square pulses. These single pulses appear to be chopped into bursts of much shorter pulses, when the drug QX-222 is present in addition to the agonist. 3. The mean duration of the bursts is comparable to or longer than the normal channel open time, and increases with increasing drug concentration. 4. The duration of the short pulses within a burst decreases with increasing drug concentration. 5. It is concluded that drug molecules reversibly block open end-plate channels and that the flickering within a burst represents this fast, repeatedly occurring reaction. 6. The voltage dependence of the reaction rates involved, suggested that the site of the blocking reaction is in the centre of the membrane, probably inside the ionic channel.

Abstract: 1. The relation between the physiological pattern of ocular dominance and the anatomical distribution of geniculocortical afferents serving each eye was studied in layer IV of the primary visual cortex of normal and monocularly deprived cats. 2. One eye was injected with radioactive label. After allowing sufficient time for transeuronal transport, micro-electrode recordings were made, and the geniculocoritcal afferents serving the injected eye were located autoradiographically. 3. In layer IV of normal cats, cell were clustered according to eye preference, and fewer cells were binocularly driven than in other layers. Points of transition between groups of cells dominated by one eye and those dominated by the other were marked with electrolytic lesions. A good correspondence was found between the location of cells dominated by the injected eye and the patches of radioactively labelled geniculocortical afferents. 4. Following prolonged early monocular deprivation, the patches of geniculocortical afferents in layer IV serving the deprived eye were smaller, and those serving the non-deprived eye larger, than normal. Again there was a coincidence between the patches of radioactively labelled afferents and the location of cells dominated by the injected eye. 5. The deprived eye was found to dominate a substantial fraction (22%) of cortical cells in the fourth layer. In other cortical layers, only 7% of the cells were dominated by the deprived eye. 6. These findings suggest that the thalamocortical projection is physically rearranged as a consequence of monocular deprivation, as has been demonstrated for layer IVc of the monkey's visual cortex (Hubel, Wiesel & Le Vay, 1977).

Abstract: 1. All complex cells in the cat's striate cortex exhibit gross non-linearities of spatial summation when tested with sinusoidal grating stimuli. Their responses to moving gratings of all but the lowest spatial frequencies are usually dominated by a component that is not modulated by the passage of the bars of the grating across the receptive field. They give responses to temporally modulated stationary gratings that consist mostly of even harmonics of the stimulus frequency and that vary little in amplitude or wave form as the spatial phase of the grating is varied. 2. We compared complex cells' receptive fields with their sensitivity to sinusoidal gratings of different spatial frequencies. Qualitatively, the receptive fields are usually two to five times wider than the bars of the gratings that stimulate them most effectively. Quantitatively, the receptive field profiles of complex cells are invariably broader than those predicted by Fourier synthesis of their spatial frequency tuning curves, and in particular lack predicted spatially antagonistic regions. 3. We further examined the receptive field organization of these cells, using pairs of stationary lines flashed synchronously on their receptive fields. If both lines are of the same polarity (bright or dark), complex cells respond to the paired stimulus much less well than they do to either of its component bars, unless the bars are separated by less than about one quarter of the width of the receptive field. If the lines are of opposite polarity, one bright and one dark, the opposite situation obtains: closely spaced bars elicit small responses, while paired bars of larger separation are much more effective. In either case, the results are independent in general character of the absolute positions of the stimuli within the receptive field; rather, they depend in a manner characteristic of each cell on the relative positions of the two bars. 4. The two-line interaction profile that plots the change in a complex cell's response to one bar as a function of the position of a second added bar corresponds closely to the receptive field profile predicted from Fourier synthesis of the cell's spatial frequency tuning curve. These profiles may thus reveal the spatial characteristics of subunits within complex cell-receptive fields. We examined the nature of the interaction between these subunits by performing several two-line interaction experiments in which the onset of the second bar was delayed some time after the onset of the first. The results suggest that neighbouring subunits interact in a facilitatory fashion: for an interval after the presentation of one bar, responses to neighbouring bars are enhanced. 5. The subunits of a complex receptive field may, by their spatial properties, determine the spatial selectivities of complex cells, while the nature of the interaction among the subunits may determine these cells' sensitivity and selectivity for moving visual stimuli...

Abstract: 1. Recordings of multi-unit sympathetic activity were made from median or peroneal muscle nerve fascicles in thirty-three healthy subjects, resting in recumbent position. Simultaneous recordings of intra-arterial blood pressure were made in seventeen subjects. The neural activity, quantified by counting the number of pulse synchronous sympathetic bursts in the mean voltage neurogram (burst incidence), was plotted against the arterial blood pressure level and the age of the subjects. The effects of spontaneous temporary blood pressure fluctuations were studied by correlating different pressure parameters of individual heart beats to the probability of occurrence of a sympathetic burst and to the amplitude of the occurring burst. 2. Between different subjects there were marked differences in burst incidence, from less than 10 to more than 90 bursts/100 heart beats. No correlation was found to interindividual differences in the arterial blood pressure level but there was a slight tendency for increasing burst incidence with increasing age. 3. Irrespective of the magnitude of the burst incidence, the bursts always occurred more frequently during spontaneous transient blood pressure reductions than during transient increases in blood pressure. When, for each heart cycle, the occurrence of a sympathetic burst was correlated with different blood pressure parameters there was regularly a close negative correlation to diastolic pressure, a low correlation to systolic and an intermediary negative correlation to mean blood pressure. There was a positive correlation to pulse pressure and to pulse interval. 4. When measured for individual heart beats, not only the occurrence but also the mean voltage amplitude of the sympathetic bursts tended to increase with decreasing diastolic pressure. 5. In a given subject when comparing heart beats with the same diastolic pressure, the occurrence as well as the amplitude of the sympathetic bursts was higher for heart beats occurring during falling than for heart beats occurring during rising blood pressure. For a given change in diastolic blood pressure, sympathetic activity changed more if pressure was falling than if it was rising. 6. The findings suggest that the sympathetic outflow is modulated by arterial baroreflex mechanisms and that transient variations in the strength of the activity are, to a large extent, determined by diastolic blood pressure fluctuations. The intimate correlation with ‘dynamic’ variations in blood pressure and the absence of correlation to the ‘static’ blood pressure level suggests that the sympathetic outflow to skeletal muscles is of importance for buffering acute blood pressure changes but has little influence on the long term blood pressure level. The difference in reflex sensitivity between falling and rising pressure indicates that acute blood pressure decreases may be buffered more efficiently than acute blood pressure increases. 7. In twenty-seven subjects baroreflex latency was calculated from the QRS-complexes in the e.c.g. to the appropriate systolic inhibition in the sympathetic activity. When recording in the peroneal nerve, the latency ranged between 1·16 and 1·49 sec and there was a positive correlation with the height of the subjects. It is suggested that such latency measurements may be used clinically to evaluate conduction in sympathetic fibres.

Abstract: 1. Recordings were made from single neurones, or small clusters of cells, in five prestriate visual areas of rhesus monkey cortex. The cells were studied for their binocularity, as well as for their orientational, motion and colour preferences. In all, 1500 cells were studied, 250 cells for each of the areas V2, V3, V3A and the motion area of the posterior bank of the superior temporal sulcus, and 500 cells for V4. All the cells referred to in this study can be placed in one prestriate area or another unambiguously. 2. The great majority of cells in all areas were binocularly driven, without monocular preferences. Within each area, there were cells that either preferred binocular stimulation markedly, or were responsive to binocular stimulation only. The ocular interaction histograms for all areas are remarkably similar when tested at a fixed disparity. 3. Over 70% of the cells in areas V2, V3 and V3A were selective for orientation. The receptive fields of cells were larger in V3 and V3A than in V2. By contrast, less than 50% of the cells in V4 and the motion area of the superior temporal sulcus were orientation selective. 4. Directionally selective cells were found in all areas. But they were present in small numbers (less than 15%) in areas V2, V3, V3A and V4. By contrast, 90% of the cells in the motion area of the superior temporal sulcus were directionally selective. 5. 8% of the cells in V2 had opponent colour properties. Cells with such properties were not found in V3, V3A or in the motion area of the superior temporal sulcus. By contrast, 54% of the cells in the V4 complex had opponent colour properties. 6. It is argued that despite its uniformity in cytoarchitectural appearance and in ocular interaction patterns, there is a functional division of labour within the prestriate cortex. Evidence for this is seen not only in the different concentrations of functional cell types in distinct areas of the prestriate cortex, but also in the differential anatomical and callosal connexions of each area.

Abstract: 1. Variation in stimulus contrast produces a marked effect on the dynamics of the cat retina. This contrast effect was investigated by measurement of the responses of X and Y ganglion cells. The stimuli were sine gratings or rectangular spots modulated by a temporal signal which was a sum of sinusoids. Fourier analysis of the neural response to such a stimulus allowed us to calculate first order and second order frequency kernels. 2. The first order frequency kernel of both X and Y ganglion cells became more sharply tuned at higher contrasts. The peak amplitude also shifted to higher temporal frequency at higher contrasts. Responses to low frequencies of modulation (less than 1 Hz) grew less than proportionally with contrast. However, response amplitudes at higher modulation frequencies (greater than 4 Hz) scaled approximately proportionally with contrast. Also, there was a marked phase advance in these latter components as contrast increased. 3. The contrast effect was significantly larger for Y cells than for X cells. 4. The first order frequency kernel was measured with single sine waves as well as with the sum of sinusoids as a modulation signal. The transfer function measured in this way was much less affected by increases in contrast. This implied that stimulus energy at one temporal frequency could affect the response amplitude and phase shift at another temporal frequency. 5. Direct proof was found that modulation at one frequency modifies the response at other frequencies. This was demonstrated by perturbation experiments in which the modulation stimulus was the sum of one strong perturbing sinusoid and seven weak test sinusoids. 6. The shape of the graph of the amplitude of the first order frequency kernel vs. temporal frequency did not depend on the amplitudes of the first order components, but rather on local retinal contrast. This was shown in an experiment with a sine grating placed at different positions in the visual field. The shape of the first order kernel did not vary with spatial phase, while the magnitudes of the first order responses varied greatly with spatial phase. 7. Models for the contrast gain control mechanism are considered in the Discussion.

Abstract: 1. Intracellular recordings were made from inner hair cells in the first turn of the guinea-pig cochlea, the recording sites being confirmed by the injection of Procion yellow dye and subsequent histology. 2. The receptor potential, in response to a pure tone burst, consisted of an AC response which followed the wave form of the stimulus and was analogous to the extracellularly recorded cochlear microphonic and a depolarizating DC response which followed the envelope of the tone burst and was analogous to the extracellularly recorded summating potential. 3. The DC response was broadly tuned at high sound pressure having a maximal amplitude of 27 mV at a sound pressure level of ca. 100 db; however the bandwidth of the response was reduced at lower sound pressure level. Isoamplitude curves for the DC response were indistinguishable from the threshold curves for auditory nerve fibres. 4. The AC response was tuned in a similar fashion to the DC response except that it was attenuated at 6-9 db/octave with respect to the DC response. It is suggested that this difference was due to the effect of membrane capacitance and resistance on the AC response. In contrast the extracellularly recorded AC component was not subject to this attenuation. 5. The total resistance and capacitance in three cells were found to be 46-61 Momega and 7.8-15.8 muF respectively. 6. Intracellular resistance changes were measured during sound stimulation, the resistance change being proportional to the DC receptor potential, indicating constant current flow through the hair cell. The current varied between 0.37 and 0.81 nA between cells. The time constant for seven cells was found to lie between 0.31 and 0.76 msec. 7. A map of the basilar membrane showing position of hair cells against characteristic frequency corresponded to the cut-off frequencies of the basilar membrane mechanical measurements and the innervation sites of spiral ganglion cells.

Abstract: 1. The consequences of repetitive activation of excitatory synaptic inputs to the CA1 pyramidal cells of rat hippocampus have been studied using in vitro techniques. 2. Single stimulation trains of 100 pulses at rates of 5-100/sec resulted in potentiation of population spike amplitudes lasting the duration of a 5 min test period in thirty-four out of thirty-five cases. Trains of 100 pulses delivered at 1/sec resulted in depression of the stimulated pathway in ten out of twelve experiments. 3. Responses to test stimulation of other excitatory inputs to the same cell population were depressed following conditioning trains at frequencies in the range 1-100/sec. Depression was seen both in the population spike amplitude (reflecting synchronous cell discharge) as well as the extracellularly recorded population e.p.s.p., and appeared to be maximal at lower frequencies. 4. Trains of antidromic stimulation of the CA1 cell population produced subsequent decreases in synaptically evoked responses, indicating that repetitive firing of pyramidal neurones or interneurones do not cause potentiation, but may be involved in heterosynaptic depression. 5. The results suggest that potentiation and heterosynaptic depression arise from different mechanisms, and that potentiation is confined to the set of terminals activated by a conditioning train, whereas the depression is generalized to the whole neurone.

Abstract: 1. Impulses in tactile units innervating the glabrous skin of the hand recorded from the median nerve of adult human subjects. The recording electrodes which were made of tungsten were inserted percutaneously in the upper arm. 2. The units were classified on the basis of their sensitivity to sustained identation and to remote stimuli. Two types of rapidly adapting units and two types of slowly adapting units were found. In accordance with earlier reports they were denoted RA and PC units, and SA I and SA II units. 3. The sensitivity profiles of the receptive fields were analysed by measuring the extent of the receptive field as a function of the identation amplitude. 4. The RA and SA I units had receptive fields with several zones of maximal sensitivity distributed over an approximately circular or oval area typically covering five to ten papillary ridges. Within this area the sensitivity was high, whereas the sensitivity diminished steeply with increasing distance from this area. 5. The PC and SA II units had receptive fields with a single zone of maximal sensitivity and gentle continuous threshold increase outside this zone. 6. The relation between the identation amplitude and the receptive field size of a unit was described by a power function. The power exponent for the RA and SA I units was well below unity, whereas the PC and SA II units had exponenets greater than unity. The variation in exponent was very small among the RA and among the SA I units. Their average exponents were therefore regarded as characteristics of the unit type. 7. The SA II units were qualitatively studied with regard to their sensitivity to lateral skin stretch. Three different types of SA II units were described with regard to the directional pattern of this sensitivity. 8. The relation of the present findings to the problem of correlation between morphological structures of nerve end-organs and physiologically defined unit types is considered. 9. Moreover, the findings, indicate that the RA and SA I units are well suited for the analysis of mechanical events on the skin surface with a high degree of spatial selectivity, whereas the PC and SA II units are suited for analysis of other mechanical events, e.g. vibration and various forms of tension in the skin and related tissues.

Abstract: 1. Longitudinal action currents were recorded from single undissected myelinated nerve fibres in intact, perfused ventral roots of normal rats and ones treated with diphtheria toxin to produce demyelination. 2. Closely spaced recording electrodes (120 micron), signal averaging and the use of a calibrating current throught the root permitted membrane currents to be determined over 240 micron lengths of nerve. Contour plotting was used to plot membrane current density as a function of space and time. 3. The previous result of Rasminsky & Sears (1972) of delayed saltation in demyelinated nerve fibres was confirmed. 4. In addition a new phenomenon of continuous conduction was observed, along distances of up to 1 1/2 times the afferent internodal distance. The continuous spatial distribution of inward current in these cases showed that electrical excitability was distributed along the internodes. 5. Internodal excitability was also revealed in demyelinated fibres by extra foci of inward current judged to be internodal on the basis of the spacing of the other (nodal) foci. 6. Continuous conduction occurred at velocities in the range of 1.1-2.3 m/sec or roughly 1/20th-1/40th of the velocities expected for normal stretches of the same fibres. 7. The continuous conduction was attributed to conduction along lengths of demyelinated axon. This was supported by estimates of 0.86 and 1.5 muF/cm2 for membrane capacity from the foot of a continuously conducted action potential. 8. The implications of internodal electrical excitability in demyelinated nerve fibres are discussed in relation to (a) recent estimates of the density of sodium channels in intact and homogenized normal nerves, (b) the pathophysiology of demyelinating disease.

Abstract: 1. The responses of forty-one muscle spindle endings, mostly in tibialis anterior, were studied in human subjects during voluntary movements of the ankle joint performed at various speeds against different external loads. 2. During slow shortening contractions, the discharge rates of spindle endings in the contracting muscle accelerated after the appearance of the first e.m.g. potentials but before sufficient force had been generated to move the limb. With some endings, the discharge rate decreased during the shortening movement while the e.m.g. activity was increasing, but it always remained higher than before the onset of contraction. If the speed of the movement was increased fewer spindle discharges were seen during muscle shortening. If the shortening contraction was opposed by an external load, so that greater effort was required to perform the same movement, more discharges were seen and the discharge pattern became less modulated by the change in muscle length. 3. These findings indicate that during shortening contractions the fusimotor system is activated together with the skeletomotor system. However, the fusimotor drive is generally insufficient to maintain a significant spindle discharge unless movement is slow or the muscle is shortening against an external load. 4. During lengthening contractions the spindle responses were greater than to passive stretch of similar amplitude and velocity, suggesting heightened fusimotor outflow. 5. During shortening and lengthening contractions small iregularities in the speed of movement occurred commonly. Unintended acceleration of a shortening movement caused a pause in spindle firing, and unintended acceleration of a lengthening movement caused an increased discharge from spindle endings. These spindle responses were associated with corresponding alterations in the discharge pattern of the voluntarily activated motor units at latencies consistent with the operation of spinal reflex mechanisms. 6. It is suggested that a functional role for the fusimotor activation during slow shortening contractions is to provide spindle endings with a background discharge so that they can detect irregularities in the movement and initiate the appropriate reflex correction.

Abstract: 1. Responses of single cells in the isolated cat spinal ganglion to GABA applied by superfusion or by iontophoresis were recorded using intracellular micro-electrodes. 2. Of the twelve structurally related compounds investigated, GABA was the most effective in its ability to produce a depolarization of the cell membrane. 3. Studies determining concentration-response relationships indicate that two to three molecules of GABA are required to combine with the GABA receptor for activation. 4. Bicuculline and picrotoxin, each act in a non-competitive manner to antagonize the GABA-induced membrane current. 5. The equilibrium potential for iontophoretically induced GABA depolarizations (EGABA) was found to be -23.5 plus or minys 6.1 mV. EGABA was independent upon [cl-]o, but independent of [Na+]o, [K+], or [Ca2+]o. 6. Intracellular injection of twenty antions (Br-, I-, NO2-, NO3-, ClO4-, SCN-, Bf4-, HS-, OCN-, ClO3-, BrO3-, F-, HCO2-, HSO3-, HCO3-, CH3CO2-, SO42-, C6H5O73-) indicated that the activated GABA receptor membrane was permeable to those anions whose hydrated diameter is no larger than that of ClO-3. 7. Restoration of the GABA depolarization to its control level after augmentation by Cl- injection had a mean time constant of 27.8 plus or minus 2.6 min. Picrotoxin did not alter this value. 8. When foreign anions were exchanged for Cl- in the perfusion solution, the ten anaions smaller or equal to ClO3-, decreased the GABA depolarization by 50-90% and increased its time course 1.5-2.0 x control. The only exception having a small radius was Br- which augmented the amplitude 10-30%. 9. The ten anions larger than ClO3- produced a biphasic effect, i.e. an initial augmentation followed by a marked (up to 100%) depression of the response. Experiments with CH3COO-, CH3SO4-, or HOCH2CH2SO3-, indicated that this depression was non-competitive.

Abstract: 1. The capacity of motor units to sprout after partial denervation and the ability of regenerating axons to suppress newly formed sprouts was examined in mouse skeletal muscle. Most experiments were performed on the peroneus tertius muscle which has 300 muscle fibres and eleven motor units ranging in strength from 1 to 35% of the total muscle tension. 2. Individual units, regardless of starting size, were able to sprout by up to 5 times their normal size following interruption of one of the two spinal roots innervating the muscle. In practive this resulted in muscles which had three or more units left intact becoming completely innervated again within 12 days. The majority of the sprouts probably innervated the old denervated end-plate sites. In the absence of re-innervation by the severed motor axons the sprouts persisted. In peroneus tertius about 60% of the sprouts giving rise to end-plates arose terminally and 40% collaterally. In soleus almost all the sprouts were terminal. 3. Re-innervation of the muscle by the severed motor axons occurred, starting from 14 days onwards after a crush injury, 19 days onwards after a cut. Re-innervation occurred even in muscles which presumably had no remaining denervated muscle fibres at the time regenerating axons reached the muscle. The re-innervating fibres grew to the original end-plate sites. 4. Following re-innervation the size of sprouted motor units apparently decreased. Thus, after re-innervation of muscles with three or more sprouted motor units, the sprouted units no longer caused contraction of all the muscle. However, the normal state of the muscle was not restored and the sprouted units continued to innervate more muscle fibres than normal, returning axons less than normal, and a small percentage of muscle fibres (ca. 10%) remained functionally innervated by axons of both sorts. 5. It is concluded that (i) in the mouse, axonal sprouting is a rapid and efficient process for restoring innervation; (ii) re-innervation of already innervated fibres can occur if the regenerating axons can return to existing end-plate sites; (iii) some of the redundant innervation is removed or repressed. 6. Possible mechanisms of competition between axon terminals are considered.

Abstract: 1. Thirty-six subjects in an isolation unit were subjected to time shifts of 12 hr, or of 8 hr in either direction. 2. The rhythms of body temperature and excretion of eight urinary constituents were studied before and after the shift, both on a usual nychthemeral routine and during 24 hr when they remained under constant conditions, awake, engaged in light, mainly sedentary activity, and consuming identical food and fluid every hour. 3. The rhythms on nychthemeral routine were defined by fitting cosine curves. On constant routine the rhythm after the shift was cross-correlated with the original rhythm, either with variable delay (or advance) or with an additive mixture between this variably shifted rhythm and the unshifted or a fully shifted rhythm. The process yielding the highest correlation coefficient was accepted as the best descriptor of the nature of adaptation. 4. A combination of two rhythms was observed more often for urinary sodium, chloride and phosphate than for other variables. 5. Adaptation appeared to have proceeded further after westward than eastward shifts, and this difference was particularly noticeable for urinary potassium, sodium and chloride. 6. Partial adaptation usually involved a phase delay, even after an eastward shift when a cumulative delay of 16 hr would be needed to achieve full adaptation and re-entrainment. 7. Observations under nychthemeral conditions often gave a false idea of the degree of adaptation. In particular, after an eastward shift the phase of the rhythms appeared to shift in the appropriate direction when studied under nychthemeral conditions whereas the endogenous oscillator either showed no consistent behaviour or, in the control of urate excretion, a shift in the wrong direction. 8. The implications for people undergoing time shifts, in the course of shift work or transmeridional flights, are indicated.

Abstract: 1. The effects of the barbiturate anaesthetic pentobarbitone on the membrane properties and amino acid pharmacology of mammalian C.N.S. neurones grown in tissue culture were studied using intracellular recording coupled with bath application, extracellular ionophoresis, or focal diffusion. 2. The addition of an anaesthetic concentration of pentobarbitone to the bathing medium abolished all spontaneous synaptic activity, but did not render individual cells electrically inexcitable nor prevent evoked synaptic acitivity. 3. Focal ionophoresis of pentobarbitone or diffusion from blunt micropipettes reversibly increased membrane conductance, effectively dampening excitability without directly affecting individual action potential characteristics. 4. Pentobarbitone-induced membrane conductance was reversibly blocked by picrotoxin. The inversion potential of the pentobarbitone voltage response depended on Cl- ion gradients and was similar to that of GABA. 5. Pentobarbitone reversibly enhanced the conductance increase produced by GABA with a variable slowing of response kinetics, shifting GABA dose-response curves to the left. Responses to glycine and beta-alanine were not affected. 6. Higher ionophoretic currents of pentobarbitone, which measurably increased membrane conductance, attenuated and markedly slowed GABA responses. Similar effects on GABA responses were observed by superimposing GABA pulses on low level GABA currents. 7. Pentobarbitone, in the absence of an increase in membrane conductance, reversibly depressed depolarizing responses to glutamate without changing response kinetics. Slower responses to acetylcholine which were associated with an apparent decrease in membrane conductance were not affected by the drug. 8. Analysis of double-reciprocal plot data suggested a non-competitive type of antagonism between pentobarbitone and glutamate. Pentobarbitone depression of glutamate was not affected by picrotoxin. 9. Both GABA and glutamate responses appeared to be equally sensitive to pentobarbitone. Specific interaction of the drug with amino acid receptor-coupled events is indicated by the requirement for pentobarbitone pipette placement close to the amino acid response site. 10. The results suggest that pentobarbitone depresses neuronal excitability by (1) directly activating post-synaptic GABA-receptor coupled Cl- conductance, (2) potentiating post-synaptic GABA-induced conductance events, probably at the level of the GABA receptor, and (3) depressing post-synaptic glutamate-induced excitation, probably at the level of the conductance mechanism.

Abstract: 1. Receptive fields of centre surround cells in the rabbit retina were investigated. There is a clear distinction between cells with sluggish responses, low spontaneous activity and slow conduction velocity (centre surround sluggish cells) and cells with brisk responses, higher spontaneous activity and faster conduction velocity (X and Y cells). The sluggish cells can be divided into sustained and transient types. X and Y cells can be distinguished from each other by their responses to a moving linear grating, a large rapidly moving object and whether or not there is a response to the alternation of certain stimuli. Some times the response to a rotating radial grating, the rate of spontaneous activity, and whether or not the response to spots and annuli was sustained or transient could also be used to distinguish these two types. The antidromic latency from electrical stimulation of the optic chiasm and the periphery effect did not distinguish X from Y. 2. Eleven colour coded units were investigated. They all gave on responses to blue light in the centre of their receptive field and off responses to green light in the periphery of their receptive field. The blue pigment had a spectral sensitivity peaking at about 465 nm. The other pigment peaked near 500 nm, like the rods but gave a response at high mesopic and probably photopic levels. In some cases there was evidence for excitatory input from the green receptors to the centre of the receptive field. All the colour coded cells had rapidly conducting axons and were on centre X cells by all criteria. 3. Eighty-five cells various types other than colour coded were tested for their thresholds at 420 nm and 590 nm. In all cases the results were explained by a pigment peaking close to 500 nm, even at high mesopic and low photopic levels, which suggests the existence of cones with a cyan pigment in them. 4. Conduction latency from stimulation at the optic chiasm was measured for cells with centre surround receptive fields and cells with more complex receptive fields. Both 'on-off' and 'on' directionally sensitive cells have short conduction latencies, overlapping X and Y cells. Orientation selective cells and local edge detectors have long conduction latencies, overlapping centre surround sluggish cells. The sample of uniformity detectors was too small to characterize...

Abstract: 1. Voltage clamp experiments using the three micro-electrode voltage clamp technique were performed on sartorius muscles of the frog. 2. By blocking potassium currents with tetraethylammonium and replacing chloride ions with sulphate a slow inward current was detected. 3. The slow inward current is mainly carried by calcium, since it is abolished by cobalt and D-600, it depends on external calcium, and is not affected by removing external sodium or by tetrodotoxin (TTX). 4. The slow inward current has a mean threshold of -40 mV, reaches a mean maximum value at ca. 0 mV of 81 microamperemetercm-2 and has a mean reversal potential of +38 mV. 5. The calcium current is inactivated by the application of 2 sec conditioning prepulses according to a sigmoid curve with V(h) = -42 mV and k = 6.2 mV. 6. The slow time course of this calcium current makes it rather unlikely that it participates in contraction during a twitch, but it might be activated during long depolarizations as potassium contractures.

Abstract: 1. A method for producing rapid [Ca2+] and [Sr2+] changes in the frog skinned muscle fibre preparation while maintaining constant all other cationic concentrations (Moisescu, 1976a, b) is described and analysed in detail. 2. Different experiments, some of them involving the Ca2+-sensitive photoprotein aequorin, as well as theoretical considerations, indicate that with this method one can produce a Ca2+ (or Sr2+) concentration change within 0.1--0.15 sec in a whole preparation having a diameter of 50 micrometer. 3. The rate of force development was similar to that observed in vivo. 4. The radial diffusion coefficient of EGTA in relaxed myofibrillar preparations was measured and found to be 4.6 x 10(-6) cm2sec-1 at 20 degrees C. 5. The sarcoplasmic reticulum in myofibrillar bundles was found to be active with respect to both Ca2+ and Sr2+ in the solutions used ([Mg2+] 1 mM; [Na] 30 mM; [K] 140-170 mM; [Cl] less than or equal to 20 mM; pH 7.10). 6. The amount of Ca released by caffeine from internal stores (previously loaded with Ca) can raise the total Ca concentration in the muscle fibre preparation by at least 1.8 mM. 7. The presence of 10 mM-caffeine in all bathing solutions reduced drastically the ability of the sarcoplasmic reticulum to accumulate both Ca and Sr.

Abstract: 1. Recordings of multi-unit sympathetic activity were made from muscle branches of the median nerve in five healthy subjects during application of lower body negative pressure (l.b.n.p.). Simultaneous recordings of arterial blood pressure were made in four subjects. The strength of the neural activity was quantitated by counting the number of pulse synchronous sympathetic bursts and their amplitudes in the mean voltage neurogram. 2. The general appearance of the sympathetic activity in pulse synchronous bursts was similar during control periods and during l.b.n.p., but during l.b.n.p. there was always an increase in the number of sympathetic bursts and usually also in the mean voltage amplitude of the bursts. 3. The probability of occurrence of a burst was correlated to different blood pressure parameters of individual heart beats and both during control periods and during l.b.n.p. there was regularly a close negative correlation to diastolic, a low correlation to systolic, an intermediate negative correlation to mean and a positive correlation to pulse pressures. 4. The changes in arterial blood pressure during l.b.n.p. were small and in most cases statistically insignificant. The observed increases in the number of sympathetic bursts during l.b.n.p. were significantly greater than what could be expected on the basis of the blood pressure changes. 5. The findings suggest that the reflex control from the arterial baroreceptors is maintained during l.b.n.p. but, since the increase of sympathetic activity during l.b.n.p. could not be explained by a change in stimulation of the arterial baroreceptors, influence from other receptor groups (presumably intrathoracic volume receptors) must also have occurred.

Abstract: 1. The cortical projections of the foveal and extrafoveal parts of the striate cortex have been compared, using conventional degeneration techniques, as well as combinations of anatomical methods. While both foveal and extrafoveal striate cortex share a common pattern of projections (to areas V2, V3 and the visual area in the medial part of the posterior bank of the superior temporal sulcus), foveal striate cortex was found to have an additional projection (to part of the cortex of the fourth visual areas, V4). The latter projection includes the posterior lip of the inferior occipital sulcus which, on anatomical grounds, is regarded as the ventral extension of V4. 2. Anatomical studies using double tracers were employed to clarify the nature of the projections from the striate cortex and from V2 to V4. In one such experiment, tritiated proline was injected into extra-foveal striate cortex and a small lesion was made in that part of V2 receiving a direct projection from the region of the striate cortex into which the radioactive tracer was injected. Only degenerating fibres (due to the lesion), and no radioactive label, was found in V4. Such an experiment showed that, unlike foveal striate cortex, the projections from extrafoveal striate cortex to V4 are not direct, but through V2. 3. In another type of anatomical experiment using double tracers, the corpus callosum was sectioned and tritiated proline was injected into foveal striate cortex. Such an experiment allowed a more accurate determination of the extent of V4, as judged from its callosal connexions, to which foveal striate cortex projects. 4. Considering the projections of V1 to areas V2, V3 and the visual area in the medial part of the posterior bank of the superior temporal sulcus, and considering the differences in the projections of foveal and extrafoveal striate cortex, it is suggested that, among other functions, the striate cortex acts as a distribution centre for the information coming over the retino-geniculo-cortical pathways, parcelling this information out to different visual areas of the prestriate cortex for further analysis.

Abstract: 1. A study has been made of twenty-three cardiac vagal motoneurones (c.v.m.s) in the nucleus ambiguus of chloralose-anaesthetized cats.2. C.v.m.s were identified as described previously (McAllen & Spyer, 1978). They were either spontaneously active (five units) or induced to fire by the ionophoresis of DL-homocysteic acid (DLH). Evidence is presented that above threshold, the DLH dose is not critical for the ability to show a baroreceptor influence.3. The influence of the baroreceptors was determined by plotting pulse-triggered histograms of c.v.m. activity. If the aortic baroreceptors were denervated, the pulse synchronous activity disappeared reversibly on carotid occlusion (eight out of eight cases). In five out of fifteen cells studied, when aortic baroreceptor pathways were intact, a small degree of cardiac modulation survived carotid occlusion.4. Estimates of the central delay of the baroreceptor-vagal reflex were made by timing the c.v.m. response to both electrical stimulation of the sinus nerve and natural baroreceptor stimulation. When both methods were used on individual units, electrical stimulation invariably gave shorter values. Natural stimulation gave values that fell into two ranges (20-60 msec and 70-110 msec), suggesting the involvement of two pathways.5. Using higher currents, four c.v.m.s were induced to fire tonically during inspiration. Their activity in this phase showed a cardiac rhythm just as during expiration. Similarly, they responded to sinus nerve stimulation throughout the respiratory cycle.6. This result is discussed in relation to the observation of others that the baroreceptor-cardiac reflex is ineffective during inspiration. It is proposed that there is no need to invoke a ;gate' early in the pathway but that this phenomenon and the present observations are best explained by summation of influences at the c.v.m. cell membrane.

Abstract: 1. The effects of KCl on the membrane potential were studied in cells from mouse islets of Langerhans identified as beta-cells by the characteristic pattern of electrical activity induced by 11.1 mM glucose. 2. In the absence of glucose, when the beta-cell membrane does not exhibit electrical activity, the dependence of the membrane potential upon external potassium [K+]o, could be described by the constant field equation using a PK/PNa ratio between 30 and 75. 3. In 11.1 mM glucose, when the beta-cell membrane potential fluctuates between a silent phase at about -50 mV and an active phase at about -40 mV giving rise to a train of spikes, the dependence of the membrane potential upon [K+]o could also be described with the constant field equation using a smaller PK/PNa of about 15, during the silent phase, and of about 8, during the active phase (foot of the spikes during the burst). 4. A bridge amplifier for measuring the changes in membrane potential during the application of pulses of current through the same micro-electrode was used to estimate the input resistance of a beta-cell. In 11.1 mM glucose, rough estimates of the membrane resistance during the silent phase averaged 1.2 X 10(8) omega. 5. The time course of the changes in input resistance of the cell when switching from 0 to 11.1 mM glucose showed a transient decrease from 0.9 X 10(8) to 0.7 X 10(8) omega followed by an increase to 1.2 X 10(8) omega. 6. The burst pattern was shown to result from the superposition of two potential changes: (a) 5--10 mV depolarization (lasting about 10 sec in 11.1 mM glucose), and (b) 10--50 mM spikes (lasting about 0.1 sec). Only the latter could be suppressed by hyperpolarizing current injection. 7. Application of pulses of current during the various phases of the electrical activity in 11.1 mM glucose enable us to compare the resistance during the silent and active phases. This was found to be oscillating between a high resistance value at about 1.2 X 10(8) omega before each burst and a low resistance value at 0.9 X 10(8) omega during the active phase at the foot of the spikes. In some cells the resistance during the silent phase remained fairly constant. In other cells it increased gradually from 1.1 X 10(8) to 1.3 X 10(8) omega measured just before each burst of spikes. 8. The observed increase in resistance induced by glucose together with the measured dependency of the membrane potential on [K+]o with and without glucose can be explained by postulating that in the presence of glucose the K+ permeability of the beta-cell membrane is reduced. 9. The oscillations between a high and a low resistance state in the presence of 11.1 mM glucose could be due to a sudden decrease in K+ permeability followed by a much larger increase in permeability to other ions, presumably Na+ and Ca2+.

Abstract: 1. The excitatory post-synaptic potentials (e.p.s.p.s.) evoked by sound stimuli were recorded intracellularly from large afferent eight nerve fibres in the sacculus of the goldfish (S1 fibres). The fish were anaesthetized with MS-222 and spike potentials were suppressed with locally applied tetrodotoxin. 2. The e.p.s.p.s. successively evoked in response to each wound wave showed a marked rundown in size, while no reduction was observed in the microphonic potentials. The amplitude of successive e.p.s.p.s was reduced keeping approximately a fixed ratio to the preceding ones, suggesting that the rundown is attributable to a depletion of transmitter quanta from the release sites. 3. The rate of rundown of successive e.p.s.p.s, however, remained almost unchanged when the intensity of the stimulus sound was changed. It was also observed that, even after the e.p.s.p.s had been completely adapted to a continuous sound, a vigorous discharge of new e.p.s.p.s was observed when the intensity of the sound was increased. 4. These findings seem to indicate that it is the size of the readily available store and not the release fraction that is changed by a change in the sound intensity. 5. The saccular macula was superfused with solutions different in Ca and Mg ion concentrations. High Ca ion concentration brought about an increase in the size of the readily available store as well as the release fraction. 6. Mechanisms underlying these observations were discussed in terms of the quantal release mechanism as well as the morphology of the release sites.

Abstract: 1 In the metathoracic ganglion of the locust some neurones can effect changes in the membrane potential of identified post-synaptic motor neurones without themselves spiking 2 These 'non-spiking' neurones have processes only within the metathoracic ganglion, and therefore are local intraganglionic interneurones 3 The absence of spikes in the interneurones reflects their normal physiological state and is not due to the experimental conditions 4 When the interneurones are depolarized by the injection of current pulses lasting several hundred milliseconds, post-synaptic motor neurones are either depolarized, or hyperpolarized, for the duration of the pulse 5 The magnitude of the change in post-synaptic voltage is graded according to the amount of presynaptic current 6 A number of physiological tests indicate that the graded effects upon motor neurones are mediated by chemical synaptic transmission For example, an evoked hyperpolarization of a motor neurone can be reversed in polarity by simultaneously hyperpolarizing the motor neurone with injected current 7 At their resting potential some interneurones tonically release sufficient transmitter to have a measurable post-synaptic effect The injection of depolarizing and hyperpolarizing currents into these interneurones effects opposite changes in post-synaptic potential 8 Other interneurones must be depolarized from resting potential before a post-synaptic effect is observed, and hyperpolarizing currents have no post-synaptic effect In these interneurones it is estimated that a depolarization of only 2 mV is sufficient to effect the release of transmitter 9 The membrane potentials of non-spiking interneurones can fluctuate by as much as 15 mV during active movements of the hind legs and individual psps as large as 5 mV can be recorded Therefore, summed psps or even single ones are expected to be the electrophysiological signals effecting transmitter release from these interneurones

Abstract: 1. A study was performed of the L-glutamate, gamma-aminobutyric acid (GABA), and acetylcholine (ACh) responses of cells in the stomatogastric ganglion of the crab, Cancer pagurus. 2. Ionophoretic or pressure application of L-glutamate revealed three classes of responses: a K+-dependent inhibition which reversed at 15-20 mV more negative than the resting potential; a Cl- dependent inhibitory response which was at equilibrium at the resting potential; and a depolarizing response. 3. Ionophoretic or pressure applications of GABA likewise produced three kinds of responses: an increase in K+ conductance, an increase in Cl- conductance, and a depolarizing response. 4. Picrotoxin (10(-6)-10(-5) M) was effective in blocking both the glutamate inhibitory responses. 10(-4) M-picrotoxin, which was necessary to produce a 50% block of the GABA-K+-dependent response, had no effect on the GABA-Cl- response. 5. beta-Guanidinopropionic acid (beta-GP) was found to be an agonist for the GABA-K+ response, but was ineffective in mimicking or blocking the GABA-Cl- response. 6. ACh applications produced large depolarizing responses with a pharmacological profile similar to that of the nicotinic ganglionic response in vertebrates. 7. The muscarinic agonist, acetyl-beta-methyl choline (MeCh), produced depolarizations which decreased in amplitude as the membrane was hyperpolarized from -40 to -100 mV. Pilocarpine and oxotremorine produced changes in the endogenous activity of ganglionic neurones. 8. Implications of these results for the identification of synaptic transmitters in the somatogastric ganglion are discussed.

Abstract: 1. The excitatory effects of acetylcholine (ACh) on an identified group of Aplysia neurones have been studied under voltage clamp in an attempt to measure the average life time. tau, of the channels opened by ACh and the elementary current, iel, flowing through these channels. The value of tau was determined both from spectral noise analysis and from current relaxations after voltage steps. Both methods lead to similar values. iel was calculated from the ratio of the variance of the ACh induced noise to the mean ACh induced current. 2. tau is increased by hyperpolarization, or by lowering the temperature. At 12 degrees C, tau = 27 msec AT -80 MV, tau = 17 msec at mV. tau is about 5 times smaller at 21 degrees C than at 12 degrees C. 3. iel increases linearly with hyperpolarization. At -80 mV, in Tris-buffered sea water, the mean value of iel was 0.8 X 10)-12) A at 12 degrees C. At 21 degrees C, this value was multiplied by 1.8. 4. The estimate of the ACh reversal potential Erev obtained by extrapolation of the relation between iel and the membrane potential V was + 30 mV. The estimate obtained from the analysis of the instantaneous current changes produced by voltage steps was + 15 mV. The difference between the two values appears to be due to the development of a K curent activated by the entry of Ca into the cell during the ACh response. This current introduces an error in opposite directions into the two estimates of Erev, which can therefore be assumed to be intermediate between + 15 and + 30 mV. An assumed value of + 20 mV yields an elementary conductance of 8 X 10(-12) omega-1 at 12 degrees C in Tris-buffered sea water. 5. The total ACh induced current measured in steady-state conditions increases more with hyperpolarization than does iel. The difference can be entirely accounted for by the fact that hyperpolarization increases tau. 6. When carbachol or tetramethylammonium is applied instead of ACh, the value of iel is identical to that found with ACh, but tau is slightly shorter (about 75%). 7. Inward ACh induced currents can still be observed in solutions where all Na has been replaced by Cs, Mg, or Ca. 8. iel increases when Na is replaced by Cs; it decreases when Na is replaced by Mg or Ca. In all Na-free solutions, tau is larger than in Na sea water: the lengthening of tau is largest for Ca sea water, smallest for Cs sea water. An interpretation of these changes of gamma is proposed. This interpretation may also account for the voltage sensitivity of gamma in normal sea water. 9. Partial replacement of NaCl by TrisCl strikingly reduces the ACh induced current. gamma is not modified by Tris substitution, and the reduction of the total current is entirely accounted for by a steep decrease of iel. Tris does not seem to affect the pore opening and closing processes, but to block the ACh controlled channel.

Abstract: 1. Two independent but neighbouring visual areas, V3 and V3A, sharing a common cytoarchitectural plan, but in each one of which the visual fields are separately represented, have been studied anatomically, functionally, and in combined anatomico-physiological experiments. 2. The properties of single cells in the two areas are so similar, judged by the techniques used in this study, that it is often impossible to tell whether any one penetration was sampling from cells in V3 or V3A. This is especially so if the cells have receptive fields in the lower hemi-quadrants, since the vertical meridian of the lower visual fields is represented along the V3-V3A boundary and since a transition from V3 to V3A along this border is not accompanied by a shift in receptive field positions of cells. 3. Since the visual fields, including the vertical meridian, are separately represented in these two areas, and since regions of vertical meridian representation are callosally connected, a simple and certain method of specifying the boundary between V3 and V3A is to examine the degeneration following section of the callosal splenium. A heavy patch of degeneration then marks the V3-V3A boundary. Within this patch, however, is a sub-patch containing fewer callosal fibres, or none at all. The boundary between V3 and V3A was taken to be at this subpatch. 4. Since the horizontal meridian is represented at the V2-V3 boundary, and since V1 projects to both these areas, sending coarse fibres to V3 and fine fibres to V2, it was found that the boundary between V2 and V3 could be precisely drawn by making a lesion in the horizontal meridian representation in V1 and noting where, in the prestriate cortex, fine fibres give way to coarse ones, without an intervening gap. 5. Double tracer anatomical experiments, in which tritiated proline was injected into V1 of animals whose callosal splenium had been sectioned, showed that whereas V3 receives a direct input from V1, V3A does not. V3A, instead, was found to receive an input from V3. Double tracer anatomical experiments were undertaken to study a possible input from V2 to V3A. Although such experiments did not reveal a direct input from V2 to V3A, they were not entirely conclusive. 6. The vast majority of cells in V3 and V3A were binocularly driven, without obvious monocular preferences. Some cells, however, though responding to stimulation of the individual eyes, summated their responses to binocular stimulation. Others responded only when both eyes were simulataneously stimulated. In any oblique penetration, cells preferring binocular stimulation only occurred either singly or in groups. 7. In an oblique penetration, the shift from a cell responding to binocular stimulation only to one responding equally well to stimulation of either eye was not necessarily accompanied by a shift in orientational preferences, shifts in the former...

Abstract: 1. Ionic currents in differentiated cells of mouse neuroblastoma clone N1E-115 have been studied under voltage-clamp conditions. 2. Depolarizing voltage steps from a holding potential of -85 mV to levels more positive than -40 mV produced fast transient inward currents followed by delayed outward currents. 3. The fast inward current is carried by Na+: it is blocked by tetrodotoxin and is absent in Na+-free solutions. Its kinetic behaviour resembles that of the Na+ current in squid giant axon. A mean value of 85 mmho/cm2 was found for the maximum Na+ conductance (GNa).4. The delayed outward current is carried primarily by K+: it is blocked by externally applied tetraethylammonium (TEA, 15 mM) and has a reversal potential (mean -71 mV) close to the theoretical K+ equilibrium potential. Its instantaneous I--V curve is linear. By analogy with the formulation of Hodgkin & Huxley (1952c), the outward current can be described by IK = -GKn2(V--EK) where GK = 12 mmho/mc2. 5. During prolonged depolarizations the delayed outward current declines. This decline, which occurs in two phases, represents a partial inactivation of the K+ conductance. 6. A weak inward current with slow activation and inactivation kinetics appears in Na+-free solution containing 10 mM-Ca2+. It is activated at a membrane potential of -55 mV and reaches its maximum at -20 mV with a time to peak of about 10 msec. This current is tetrodotoxin-resistant, reversibly blocked by Co2+ (5mM) and is suggested to be carried by Ca2+. 7. An increase in the external divalent cation concentration results in a parallel shift of the steady-state I--V curve along the voltage axis in positive direction. The activation of delayed outward currents is suggested not to depend on Ca2+ influx. 8. It is concluded that separate voltage-dependent Na+, K+ and Ca2+ channels exist in the differentiated neuroblastoma membrane with kinetic and pharmacological properties similar to those observed in non-mammalian preparations.