bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra‐axonal diffusion of [3H]acetylcholine and [3H]gamma‐aminobutyric acid in a neurone of Aplysia.
Authors: Koike H , Nagata Y
Published: December 2014

1. [3H]acetylcholine (ACh) or [3H]gamma‐aminobutyric acid (GABA) was injected into the cell body of a cholinergic neurone of Aplysia kurodai. 2. [3H]ACh moved down the axon at a maximum speed of 2.5 mm/sec at 20 degrees C. 3. 20 mM‐colchicine suppressed this movement, but some passive movement of radioactivity was noted along the axon. 4. Profiles of the passive movement coincided with theoretically obtained diffusion profiles. 5. The diffusion coefficient of ACh in the axoplasm was estimated. It was 3 x 10(‐6) cm2/sec at 5 degrees C, 4 X 10(‐6) cm2/sec at 15 degrees C and 6.5 x 10(‐6) cm2/sec at 30 degrees C. The Q10 was 1.35, the activation energy was about 5 kcal/degrees C. These diffusion coefficients were lower than that of free diffusion of ACh (8 x 10(‐6) cm2/sec at 18 degrees C, Fatt, 1954), and assumed to be reasonable, if one considers frictional resistivity of axoplasm in the diffusion of ACh molecules. 6. [3H]GABA diffused similarly to ACh, and the diffusion coefficients agreed with the estimated value when the molecular size differences were taken into account. 7. Both ACh and GABA seemed to diffuse in soluble form or as single molecules in the axoplasm. 8. Intra‐axonal diffusion is very effective for short distances.
A voltage‐clamp study of the light response in solitary rods of the tiger salamander.
Authors: Bader C R , Macleish P R , Schwartz E A
Published: December 2014

1. Single, isolated, rod photoreceptors were obtained by enzymatic dissociation of the tiger salamander (Ambystoma tigrinum) retina. These solitary cells retained the morphological features of rods of the intact retina and could be maintained in culture for several days. Solitary cells were penetrated with one or two micropipettes and their electrophysiology was studied by the voltage‐clamp technique. 2. Intracellular recording with two micropipettes demonstrated that the inner segment of a solitary rod was effectively isopotential with the outer segment. 3. The time course of the voltage response to a flash resembled that of responses observed in rods in the intact retina. At low light intensities the response reached a peak in approximately 0.7 sec and then slowly declined. At high light intensities the time to peak response decreased and an initial transient arose as the response, after reaching the peak, quickly decreased to a less polarized plateau. 4. The normal voltage response could be compared with the current observed during a voltage clamp. At low light intensities the time course of the current response resembled the time course of the voltage response. When light intensity was increased the time course of the current response differed from the voltage response in that the time to peak amplitude remained relatively constant and an initial transient did not occur. It was possible to predict the current response produced by any intensity of light by using (i) an empirical equation which reproduced the time course of a dim response and (ii) the Michaelis‐Menten equation. 5. The time course of the voltage‐clamp current produced by a flash was the same at different values of maintained voltage. 6. The maximum amplitude of the voltage‐clamp current produced by a flash or step of light was a non‐linear function of membrane potential. It was relatively constant within the physiological range, decreased as the membrane potential was moved toward 0 mV, reversed polarity between 0 and 10 mV, and rapidly increased in magnitude as membrane potential was made more positive. Although this current was voltage dependent, no time dependence was evident (recording resolution greater than or equal to 5 msec). 7. Voltage‐clamp experiments demonstrated an inward current which slowly developed after a hyperpolarizing voltage step. The effect of this voltage and time dependent current was to reduce, after a delay, the polarization initiated by light.
Ionic conductances of membranes in ciliated and deciliated Paramecium.
Authors: Machemer H , Ogura A
Published: December 2014

1. Paramecium caudatum was deciliated with ethanol. The ionic conductance of the membrane was investigated with constant current, voltage clamp and mechanical stimuli. 2. The resting potential was not modified by the removal of the cilia. The dependence of the resting potential on the extracellular concentrations of Ca and K was the same in deciliated and control cells. 3. The input resistance in deciliated and ciliated cells increased after the ethanol treatment. 4. The membrane capacitance decreased to 48% after deciliation, suggesting that the ciliary surface area is equal to the somatic surface area. 5. Deciliation completely removed the regenerative response (graded action potential) elicited by depolarizing current pulses or mechanical stimuli. 6. Deciliated cells retained the depolarizing and hyperpolarizing mechanoreceptor responses. 7. Voltage‐clamp experiments demonstrated the loss of the early inward current in deciliated cells; it was restored during ciliary regeneration. Steady‐state current‐voltage relationships were unchanged by deciliation. 8. The time courses of the recovery of the membrane capacitance and of the early inward current were similar, suggesting that the number of voltage‐sensitive Ca channels is proportional to the ciliary membrane area. 9. We conclude that the voltage‐sensitive Ca channels reside in the ciliary membrane (in confirmation of Dunlap, 1976; Ogura & Takahashi, 1976), while mechanoreceptor channels, rectifier channels and resting conductances are localized in the somatic membrane.
Pigment transformation and electrical responses in retinula cells of drone, Apis mellifera male.
Authors: Bertrand D , Fuortes G , Muri R
Published: December 2014

1. Receptor potentials in honeybee drone retinula cells were recorded with intracellular micro‐electrodes in the dorsal part of the superfused retina. The light stimuli were sufficiently weak that the response amplitude was proportional to the intensity. 2. Responses to stimuli of different wave‐lengths, although of different amplitude, all had the same time course. 3. The maximal sensitivity in all the cells recorded from was to a wave‐length between 450 and 460 nm. 4. Microspectrophotometry showed the presence of a pigment with two stable states, interconvertible by light, absorbing maximally at 445 nm (rhodopsin) and 505 nm (metarhodopsin). 5. There was a good match between the absorption spectrum of rhodopsin and the spectral sensitivity of retinula cells. 6. Transformation of a large fraction of rhodopsin to metarhodopsin by light reduced the sensitivity of the retinula cell but did not alter the shape of the relative spectral sensitivity curve or the time course of the responses. 7. It is concluded that for weak lights the receptor potential is determined only by the number of rhodopsin molecules that absorb photons: neither the presence of metarhodopsin nor its phototransformation to rhodopsin produces a detectable effect.
Amylase secretion in the rabbit parotid gland when stimulating the sympathetic nerves during parasympathetic activity
Authors: Gjörstrup Per
Published: December 2014

1. In anaesthetized rabbits amylase secretion from the parotid gland was investigated. Secretion was evoked by sympathetic nerve stimulation, either alone or superimposed on a parasympathetic background secretion, imitating the resting secretion present in the waking animal.

2. Sympathetic nerve stimulation at frequencies below 1 Hz was alone subthreshold for fluid secretion, but could greatly increase the amounts of amylase present in fluid secretion produced by parasympathetic nerve stimulation. The amylase output due to sympathetic nerve stimulation alone at 10 Hz did not exceed that seen in response to a stimulation at 1 Hz superimposed on parasympathetic activity.

3. The amylase output in response to superimposed sympathetic stimulation was not influenced by the rate of fluid secretion, which was altered by stimulating the parasympathetic nerves at different frequencies.

4. Sympathetically‐evoked amylase secretion was abolished after β1‐block. The amylase secretion remaining on parasympathetic activation was sparse.

5. It is concluded that secretion of amylase in response to sympathetic nerve stimulation requires the presence of a parasympathetic fluid secretion to be washed along the glandular ducts. Parasympathetic activity may also augment the sympathetic effect on amylase secretion.
The spread of sensitization of polymodal nociceptors in the rabbit from nearby injury and by antidromic nerve stimulation.
Authors: Fitzgerald M
Published: December 2014

1. Ninety‐three polymodal nociceptor units with unmyelinated axons were isolated from rabbit sural nerves. Twenty‐three were used for control data. These showed normal sensitization on repeated heating of their receptive fields, measured here as a drop in mean heat threshold. 2. Small injuries were made 5 (n = 15) or 10 (n = 12) mm outside the receptive fields of some polymodal nociceptors. This resulted in the development of spontaneous firing and lowered thresholds to heating of the receptive field. 3. Local anaesthetic previously injected into the site of injury blocked this spread of heat sensitization. Previous injection of saline had no effect. 4. Antidromic stimulation of the sural nerve, proximal to the recording site, also resulted in heat sensitization of polymodal nociceptors (n = 10). 5. Possible mechanisms for the spread of sensitization of polymodal nociceptors from nearby injury are discussed. Analogies are drawn between these results and those of Lewis (1935‐‐36) on the spread of cutaneous ;yperalgesia around a skin injury in man.
Detection of tactile stimuli. Thresholds of afferent units related to psychophysical thresholds in the human hand.
Authors: Johansson R S , Vallbo A B
Published: December 2014

1. Psychophysical thresholds were determined at 162 points in the glabrous skin area of the human hand when slowly rising, triangular indentations of controlled amplitudes were delivered with a small probe. The method of constant stimuli was used with either the two alternative forced choice or the yes‐no procedure. It was found that the distribution of the psychophysical thresholds varied with the skin region. Thresholds from the volar aspect of the fingers and the peripheral parts of the palm were low and their distribution was unimodal with a median of 11.2 micrometers. In contrast, there was an over‐representation of high thresholds when observations from the centre of the palm, the lateral aspects of the fingers and the regions of the creases were pooled, and the distribution was slightly bimodal with a median of 36.0 micrometers. 2. Nerve impulses were recorded from single fibres in the median nerve of human subjects with percutaneously inserted tungsten needle electrodes. The thresholds of 128 mechanosensitive afferent units in the glabrous skin area of the hand were determined when stimuli were delivered to partly the same points as stimulated for the assessment of the psychophysical thresholds. Of the four types of units present in this area the Pacinian corpuscle (PC) and rapidly adapting (RA) units had the lowest thresholds with medians of 9.2 and 13.8 micrometers, followed by the slowly adapting type I and slowly adapting type II units with medians of 56.5 and 33.1 micrometers. There was no indication of a difference between thresholds of units located in different skin areas. 3. In the region of low psychophysical thresholds there was good agreement between the thresholds of the rapidly adapting and Pacinian corpuscle units and the psychophysical thresholds, particularly at the lower ends of the samples. In the skin regions of high thresholds, on the other hand, practically all psychophysical thresholds were higher than the thresholds of the most sensitive afferent units. Moreover, simultaneous recording of nerve impulses during a detection task indicated that subjects did not detect stimuli strong enough to elicit several impulses in afferent units in this region. 4. Circumstantial evidence led to the conclusion that detection was dependent on one impulse in one or a few rapidly adapting units under optimal conditons in the region of low psychophysical thresholds, whereas it seemed unlikely that activity in Pacinian corpuscle units was crucial. 5. The findings are consistent with the interpretation that human subjects are able to detect an input consisting of a single impulse in a single rapidly adapting unit.
Electrophysiological analysis of pathways connecting the medial preoptic area with the mesencephalic central grey matter in rats.
Authors: MacLeod N K , Mayer M L
Published: December 2014

1. An electrophysiological study of ascending and descending connexions between the dorsal raphe region of the mesencephalic periaqueductal grey matter and the medial preoptic area has been performed in dioestrous female rats anaesthetized with urethane. 2. Extracellular action potentials recorded from 208 neurones in the medial preoptic area were analysed for a change in excitability following stimulation of the periaqueductal grey matter. 174 neurones were also tested for changes in excitability following stimulation of the mediobasal hypothalamus. 3. Stimulation of the periaqueductal grey matter at 1 Hz was rarely effective, but short trains of pulses (three at 100 Hz) usually caused an initial inhibition (62.5% of 208) of both projection identified and adjacent neurones of the medial preoptic area, at latencies of 5‐‐90 msec (mean 34.1 +/‐ 1.4 msec). Inhibition following stimulation of the mediobasal hypothalamus occurred less frequently (34%) and at shorter latency (mean 12.0 +/‐ 1.8 msec; n = 48). 4. Less frequently (10.6%) periaqueductal grey matter stimulation caused an initial excitation of preoptic neurones at latencies of 15‐‐180 msec, (mean 35.3 +/‐ 7.2). Initial excitation following mediobasal hypothalamus stimulation was stronger, occurred more frequently (29%) and at shorter latencies (range 3‐‐60 msec, mean 13.1 +/‐ 1.5). Following such initial excitation, inhibition of spontaneous or ionophoretically evoked activity occurred more frequently following mediobasal hypothalamic stimulation, than after periaqueductal grey matter stimulation. 5. Twenty‐four neurones displayed antidromic invasion following periaqueductal grey matter stimulation. Latencies for invasion ranged from 13 to 50 msec (mean 25.5 +/‐ 2.0 msec) and are suggestive of an unmyelinated projection. Occasionally an abrupt decrease in latency followed an increase in stimulus intensity. Antidromic invasion from mediobasal hypothalamus was characterized by a shorter latency (mean 12.5 +/‐ 0.7 msec; n = 43). A period of reduced excitability lasting 40‐‐100 msec followed antidromic invasion from either site. 6. Antidromic responses to paired mediobasal hypothalamic or periaqueductal grey matter stimuli at 5 msec intervals revealed an increased latency of invasion of the second response, due to the partial refractory period of the neurone. Five cells showed a decreased latency of invasion at stimulus separations of 10‐‐150 msec, interpreted as evidence of a supranormal period. Changes in conduction velocity during the supranormal period may give rise to a variable latency of invasion of spontaneously active cells. 7. These results provide evidence for direct, reciprocal connexions between the midbrain central grey and the medial preoptic area. These circuits may play a role in controlling neuroendocrine and behavioural aspects of reproductive functions.
Interactions between extraocular proprioceptive and visual signals in the superior colliculus of the cat.
Authors: Donaldson I M , Long A C
Published: December 2014

1. The responses of units in the superficial layers of the superior colliculus to stretch of extrinsic ocular muscles (e.o.m.) and to visual stimuli, delivered singly and paired at various inter‐stimulus intervals, were studied in chloralose‐anaesthetized cats. 2. Most units responded to visual stimuli and about half also gave phasic excitatory responses to stretch of e.o.m. 3. Signals from the e.o.m. of each eye reach both superior colliculi; only those in the colliculus ipsilateral to the e.o.m. stretched were studied in detail. 4. A variety of control experiments provided evidence that the signal leading to the responses to e.o.m. stretch was extraretinal. The strong probability is that the receptors responsible were in the extrinsic ocular muscles or their tendons. 5. Of fifty‐six units, twenty‐four (43%) showed definite interactions between the effects of visual stimuli delivered to the left eye and those due to stretch of e.o.m. of the right eye whose retina had been destroyed. 6. Interactions were found with both stationary and moving visual stimuli. They involved either enhancement or reduction (sometimes abolition) of the response to either e.o.m. or visual stimulation, particularly the latter. 7. Units with interactions showed one of three types of behaviour. (1) Excitatory responses to visual and e.o.m. stimuli given singly, and interactions when the two types of stimulus were paired at some time intervals. Suppression and abolition of visual responses by preceding e.o.m. stretch was common. (2) Units with little or no excitatory response to e.o.m. stretch applied alone, but with showed reduction of their visual responses by preceding e.o.m. stretch. (3) Units with minimal responses to either type of stimulus presented alone but which gave markedly enhanced responses when visual and e.o.m. stimuli were paired. 8. These interactions between proprioceptive and retinal signals are thought to allow retinal image movements which result from saccades to be distinguished from those due to movement of objects in the external world.
Acetylcholine release evoked by single or a few nerve impulses in the electric organ of Torpedo.
Authors: Dunant Y , Eder L , Servetiadis‐Hirt L
Published: December 2014

1. The acetylcholine (ACh) store in the Torpedo electric organ was partially labelled with choline and acetate at the same molar concentration but with different isotopes. Under these conditions the two precursors were incorporated into ACh in a ratio 1 to 1. 2. After a single electrical stimulus, or a brief burst of stimuli, the compound electroplaque potential (e.p.p.) was recorded and the radioactive choline and/or acetate counted in the perfusion fluid, providing a sensitive assay for ACh release in the absence of anticholinesterase drugs. 3. The so‐called depression of transmission was found to be due to progressive impairment of ACh release in the successive impulses evoked by repeated stimuli. 4. In a pair of impulses separated by 50 ms interval, less ACh was released by the second than by the first impulse; this explained why the size of the second e.p.p. was depressed, using a direct measurement of ACh. 5. In repetitive stimulations of longer duration, the maximum rate of release declined as the activity was prolonged. Thus the tissue progressively lost its ability to ensure release at high frequencies. 6. An unexpected finding was that anticholinesterases like eserine or pre‐treatment with fluostigmine (DFP) greatly reduced ACh release even by a single impulse. 7. Evoked ACh release and e.p.p. amplitude were both maximum between 10 and 20 degrees C. At higher temperatures, the evoked release decreased as the spontaneous release increased. 8. Changes in external Ca2+ and Mg2+ produced similar changes in the e.p.p. and evoked ACh release. The dose‐‐response curve for Ca dependency of ACh release was very steep with a Hill's coefficient of 3.2. 9. With a single stimulus in the presence of 4‐aminopyridine, there was a dramatic enlargement of the e.p.p. and a still larger potentiation of the evoked ACh release. 10. It has been possible with this approach to avoid the inconveniences often encountered in simliar studies, i.e. repetitive stimulation, low Ca solutions and cholinesterase inhibition. This permitted a good correlation between electrophysiological and biochemical estimates of transmitter release even by a single nerve impulse.
Irreverisble differential block of A‐ and C‐fibres following local nerve heating in the cat.
Authors: Klumpp D , Zimmermann M
Published: December 2014

1. Local heating of a nerve was used to block conduction in the myelinated or A‐fibres while preserving normal function in most of the non‐myelinated or C‐fibres. Compound action potentials of A‐ and C‐fibres, and impulses in single C‐fibres were recorded to measure the block. 2. Most experiments were done on the posterior tibial nerve of the cat's hind limb. Conducted heat was applied in successive periods of about 2 min each to 15 mm of the exposed nerve. 3. The range of temperatures used was between 45 and 52 degrees C. Below 46 degrees C no conduction block was obtained. With increasing temperature the cumulative time of heating required to produce a block in at least 99% of A‐fibres decreased from around 110 min at 46.5 degrees C to 10 min at 51 degrees C. 4. In the posterior tibial nerve the C‐fibre compound action potential was reduced to 0.66 of control (mean of twenty‐two experiments) when the A‐fibre action potential was less than 1% of control. The corresponding value of this selectivity coefficient was 0.20 in seven superficial peroneal and sural nerves. 5. Once a conduction block of A‐fibres was reached the remaining C‐fibres showed normal functioning, including conduction of repetitive impulses at up to 30 Hz evoked by electrical nerve and adequate skin stimulation. C‐fibre conduction persisted for at least 33 h, but not longer than 3 days. 6. This pure C‐fibre nerve might be useful for studying central nervous system effects of C‐fibres.
Light responses of ganglion cells in the retina of the turtle
Authors: Bowling D. B.
Published: December 2014

1. Recordings were made from single axons of 218 ganglion cells in the optic nerve of the turtle, Pseudemys scripta elegans. Responses to light stimuli were used to classify 182 of the cells into four functional groups.

2. Movement‐sensitive cells (113 units) responded best to moving stimuli independent of the stimulus colour or direction of motion. Their receptive fields were organized into antagonistic centres and surrounds with the same spectral sensitivity. Based on their patterns of response they were of three types: ON‐centre, OFF‐centre, and ON—OFF.

3. Directionally selective cells (sixty‐five units) responded best to stimuli that moved in one preferred direction and not to stimuli that moved in the opposite direction. Their receptive fields had antagonistic centres and surrounds with the same spectral sensitivity. An area of silent inhibition could be shown on one side of the receptive fields. The preferred directions appeared to fall into three groups separated by about 120 degrees. Response patterns were of two types; OFF‐centre and ON—OFF.

4. Sensitizable colour cells (two units) had centre‐surround organization with red‐green opponent responses from both the centre and the surround (double opponent cells). In addition, the sensitivity to either of the opponent colours was effectively turned on or off by a steady background of the other opponent colour.

5. Orientation cells (two units) responded best to moving bars of specific orientations in the visual field. Their receptive fields consisted of adjacent mutually antagonistic areas with linear boundaries.

6. Under photopic conditions all of the ganglion cells were most sensitive to light near 630 nm wave‐length, the spectral maximum of the red‐sensitive single cones in the turtle retina. About 75% of the cells had a secondary spectral peak near 560 nm, the spectral maximum of the green‐sensitive single cones. Three cells had unusually broad sensitivity extending into the blue portion of the spectrum. Over half of the cells received additional input from rods as evidenced by a shift in spectral sensitivity and increases in latencies and receptive field sizes with dark‐adaptation.

7. Measurements of the absolute sensitivity of the ganglion cells showed that a threshold response required absorption of several hundred photons in the red‐sensitive cones of the receptive field centre. After 10 min dark adaptation the rods required absorption of about 20 photons.
Nickel and calcium ions modify the characteristics of the acetylcholine receptor‐channel complex at the frog neuromuscular junction.
Authors: Magleby K L , Weinstock M M
Published: December 2014

1. Miniature end‐plate currents (m.e.p.c.s) and acetylcholine induced current noise were recorded from the cutaneous pectoris muscle of the frog with the voltage‐clamp technique. Analysis of current noise was used to estimate mean single channel current and the mean lifetime of an open channel. 2. Adding Ni2+ or Ca2+ to the bathing solution reduced the amplitude of the m.e.p.c.s. Ten mM‐Ni2+ decreased the amplitude 64%, while raising Ca2+ from 2 to 10mM decreased the amplitude 35%. 3. The decreased amplitude of the m.e.p.c. in Ni2+ and increased Ca2+ can be explained by a decrease in single channel current. Ten mM‐Ni2+ decreased mean single channel current 64% while raising Ca2+ from 2 to 10 mM decreased single channel current 28%. 4. The decrease in single channel current was due to a decrease in the driving potential and single channel conductance. Ten mM‐Ni2+ and Ca2+ shifted the reversal potential for the m.e.p.c. about 10 mV negative from the control value of ‐4.6 mV; at the same time single channel conductance was decreased 59% in Ni2+ and 18% in increased Ca2+. 5. In contrast to the similar direction of effects of Ni2+ and Ca2+ on m.e.p.c. amplitude, reversal potential, and single channel conductance, Ni2+ and Ca2+ had different effects on m.e.p.c. time course. Ten mM‐Ni2+ increased the time constant of m.e.p.c. decay 80% while raising Ca2+ from 2 to 10 mM decreased the time constant of decay 17%. 6. Ni2+ and Ca2+ also had different effects on single channel lifetimes. Ten mM‐Ni2+ increased channel lifetime about 50%, while raising Ca2+ from 2 to 10 mM did not significantly affect channel lifetime. 7. These results suggest that changes in single channel lifetime and conductance due to ionic influences are not necessarily tightly coupled. The results also suggest that the effects of both Ni2+ and Ca2+ on channel lifetime cannot be accounted for in terms of a simple surface potential hypothesis.
Calcium‐activated transient outward current in calf cardiac Purkinje fibres.
Authors: Siegelbaum S A , Tsien R W
Published: December 2014

1. The possibility that the transient outward current of calf cardiac Purkinje fibres depends on intracellular calcium was investigated using a two micro‐electrode voltage clamp. 2. Upon removal of Cao and replacement with Sr or Ba, the transient outward current was strongly suppressed. At the same time a large slow inward current was revealed. 3. Partial removal of Cao with replacement by Mg also diminished the transient outward current. The inhibition was not due to voltage shifts in the inactivation curve. 4. The kinetics of the peak transient outward current were compared with the kinetics of peak twitch force, an approximate measure of the level of Cai. The two signals were related in a linear manner during beat‐dependent changes with trains of voltage clamp depolarizations. 5. Tension and transient outward current were also found to inactivate with a similar dependence on pre‐potential and recover from inactivation along a similar time course. Both processes activated with membrane depolarization in a similar manner. 6. Intracellular injection of EGTA reduced the magnitude of the transient outward current and the twitch contraction. 7. The inhibition of outward current following EGTA injection was more pronounced for strong depolarizations. With pulses negative to ‐ 10 mV, there was often little apparent change in the peak net outward current. 8. All lines of evidence support the hypothesis that the transient outward current is activated by intracellular Ca. 9. The functional significance of the transient outward current is discussed. Since a Ca‐activated outward current would automatically offset slow inward Ca current, such a system may help prevent arrhythmogenic slow responses in the His‐Purkinje network.
The pattern of breathing following step changes of alveolar partial pressures of carbon dioxide and oxygen in man
Authors: Gardner W. N.
Published: December 2014

1. The pattern of breathing during the approach to the steady state following step changes of end‐tidal PCO2 and PO2 has been determined in normal conscious human subjects. Three types of step were studied: (a) steps of PA, CO2 against a constant background of hyperoxia (PA, O2 ∼ 200), an almost pure intracranial chemoreceptor stimulus, (b) steps of PA, O2 between ∼ 50 and 80 torr against a background of constant mild hypercapnia, an arterial chemoreceptor stimulus, and (c) steps of PA, CO2 against a background of constant hypoxia (PA, O2 ∼ 50), a mixed stimulus. Steps were small and the responses barely detectable by the subjects.

2. Steps of CO2 in hyperoxia produced the slowest approach to the steady state. A single exponential fitted the ventilation response up to about 4 min (mean half time 83 sec for the ‘up’ and 69 sec for the ‘down’ transients). During the transient the pattern of change of tidal volume (VT) and expiratory time (TE) was the same as in the steady state. Inspiratory time (TI), however, in the early part of the transient, changed in the opposite direction to TE, returning to its steady value only after 1½‐3 min. This effect occurred in both ‘up’ and ‘down’ transients and resulted in a smaller change of respiratory frequency than would have been predicted from the steady‐state response.

3. Hypoxic steps produced the fastest approach to the steady state with mean half‐times for ventilation of 10·9 sec for the ‘up’ transients and 6·6 sec for the ‘down’. TI followed the same pattern during the transient as in the steady state, whereas TE, following the step out of hypoxia, lengthened to far beyond its final steady value within five breaths of the step, only returning to its steady‐state value 3‐4 min after the step. This resulted in an exaggerated change of frequency during the early part of the transient.

4. Steps of CO2 in hypoxia, a mixed peripheral and central chemoreceptor stimulus, showed a ventilation response which was best fitted by two exponentials, the half‐times of which were consistent with those obtained for the separate responses. The patterning was also consistent with a mixed response, more so for TI than for TE.

5. The steady‐state pattern derived from the pre‐switch means was consistent with the pattern previously described.

6. Possible mechanisms are discussed. It is suggested that these results could explain the different patterns seen in the past by those using re‐breathing and steady‐state techniques.

7. The validity of using one or two breath oxygen or nitrogen tests (or other similar tests) as a quantitative measure of the hypoxic response in man is questioned.
Central respiratory effects of carbon dioxide, and carotid sinus nerve and muscle afferents.
Authors: Eldridge F L , Gill‐Kumar P
Published: December 2014

1. In anaesthetized and paralysed cats, artificially ventilated and with the vagi and carotid sinus nerves cut, the effects of (a) changing end‐tidal CO2, (b) stimulation of carotid sinus nerves, and (c) squeezing the calf muscles, on neural respiratory output have been studied. 2. The peak value of integrated phrenic activity, which is the neural equivalent of tidal volume (VTn), the rate of rise of integrated phrenic activity (Slope), inspiratory duration (TI), expiratory duration (TE), and total cycle length (Ttot) were measured. It was found that Slope‐VTn, VTn‐Ttot and VTn‐TE relationships were similar whether respiration was stimulated by carotid sinus nerve stimulation or by increasing end‐tidal CO2. However, when respiration was stimulated by squeezing the calf muscles, a given Slope was associated with a smaller VTn and a given VTn was associated with smaller Ttot and TE values than obtained with the other two inputs. 3. It is concluded that these results are compatible with the hypotheses that (1) inputs from central and peripheral chemoreceptors have similar actions at various sites in the respiratory centre complex, and (2) afferents activated by squeezing the limb muscles have additional facilitatory actions on mechanisms terminating inspiration and expiration.
Intensity of sensation related to activity of slowly adapting mechanoreceptive units in the human hand
Authors: Knibestöl M. , Vallbo Å. B.
Published: December 2014

1. Impulses were recorded from single afferent fibres in the median and ulnar nerves of human subjects. The response of slowly adapting mechanosensitive units with receptive fields in the glabrous skin of the hand were studied when rectangular indentations of varying amplitudes and invariant time duration were delivered. Simultaneously the subject was asked to estimate the magnitude of his sensation associated with the stimuli.

2. Stimulus—response plots of the afferent units were constructed and compared with the psychophysical magnitude estimation plots.

3. The stimulus—response data of the afferent units fell along monotonous curves which were largely decelerating when stimuli above the static threshold were taken into account. When responses below the static threshold were taken into account many plots were S‐shaped.

4. The psychophysical plots were monotonous and either decelerating, linear or accelerating.

5. Power functions were fitted to the two sets of data. The group average differed considerably with regard to the exponent of the fitted functions which was 0·7 for the neural and 1·0 for the psychophysical function.

6. There was considerable variation between shapes of curves derived from individual test points. The range of exponents for the neural function was 0·26‐1·92 and for the psychophysical function 0·36‐2·09. The variation in psychophysical functions was partly accounted for by relatively stable inter‐subject differences, whereas no such inter‐subject difference was evident for the neural functions, which seemed to vary randomly.

7. There was no indication of a correlation between the shapes of the neural functions and the shapes of the psychophysical functions when data from individual subjects or individual test points were compared. Moreover, when two groups of data were considered, one with accelerating and one with decelerating psychophysical functions, the associated neural functions did not differ between the two groups.

8. It was concluded that the hypothesis of a close agreement between the stimulus—response functions of slowly adapting mechanoreceptors in the human hand and the psychophysical magnitude estimation functions is not tenable. This was evident when average group data were compared as well as when data from individual subjects and individual target points were compared. The findings suggest that the shapes of the psychophysical magnitude estimation functions are highly dependent on central mechanisms and are not a direct function of the properties of the afferent units as has been claimed in previous investigations.
The intracellular sodium activity of sheep heart Purkinje fibres: effects of local anaesthetics and tetrodotoxin
Authors: Deitmer Joachim W. , Ellis David
Published: December 2014

1. The intracellular Na activity (aNai) of quiescent sheep heart Purkinje fibres has been measured using Na+‐sensitive glass micro‐electrodes. The effects of local anaesthetics (procaine and lidocaine) and tetrodotoxin (TTX) have been investigated.

2. Local anaesthetics reduced the steady‐state level of the intracellular Na activity in a dose‐dependent manner. The highest concentrations used (10−2
M) reduced the intracellular Na activity by about 25%.

3. TTX decreased the steady‐state level of the intracellular Na activity. At a concentration of 10−6 g/ml. (3·13 × 10−6
M), TTX produced a decrease in intracellular Na activity of approximately 10%.

4. The initial rate of rise of the intracellular Na activity upon addition of the cardioactive steroid strophanthidin (10−5
M) was used to estimate the net passive Na influx.

5. Procaine (5 × 10−4
M) caused a 50% reduction of this rate of rise of the intracellular Na activity. The highest concentration of procaine used (10−2
M) decreased the rate of rise by approximately 80%.

6. Procaine (5 × 10−3
M) also reduced the rate of rise of intracellular Na produced by the removal of external K (Ko), and prevented the large depolarization associated with the absence of Ko.

7. TTX also produced a decrease in the rate of rise of the intracellular Na activity that occurs upon addition of strophanthidin. A maximum effect was produced in our experiments at a TTX concentration of 10−6 g/ml. At this concentration the rate of rise of intracellular Na activity was reduced by approximately 40% at a membrane potential of ‐70 mV.

8. We conclude from our experiments that the effects of local anaesthetics and TTX on the intracellular Na activity are brought about by a reduction of the Na permeability of the cell membrane, and that at the normal resting potential, Na entry through TTX‐sensitive channels contributes greatly to the total net Na influx.
The superior colliculus and movements of the head and eyes in cats
Authors: Harris Laurence R.
Published: December 2014

1. The superior colliculus has been studied in alert cats which were restrained and whose head and eye movements were monitored.

2. Microstimulation within the rostral part of the colliculus, which represents the central 25 deg of the visual field, evokes saccadic eye movements that carry the area centralis to that region of visual space previously occupied by the receptive fields of the cells that were stimulated (‘foveation’). These saccades are not generally accompanied by a movement of the head.

3. At more caudal locations the visual receptive fields of collicular neurones lie at a greater eccentricity relative to the area centralis than the maximum possible deviation of the eyes from the central position in normal circumstances. At these sites electrical stimulation produces a combined movement of the head and eyes whose co‐ordination is identical to that of natural gaze changes in response to novel stimuli. Prolonged stimulation results in the addition of further co‐ordinated eye‐head movements.

4. The addition of a movement of the head does not increase the area of visual space that may be foveated in a single gaze change. Movements of the head are compensated by the vestibulo‐ocular reflex. The visual receptive fields of cells at more caudal locations cannot be foveated by a single gaze change.

5. A third class of response to electrical stimulation is also occasionally found in the caudal part of the colliculus. The head movement often begins before an accompanying eye movement and continues smoothly for the entire stimulation duration or until limited by the range of mobility.

6. Electrical microstimulation was never found to produce so‐called ‘goal‐directed eye movement, in which the eyes move, in a single saccade, to a fixed orbital position regardless of their starting position.

7. Ninety‐nine cells were recorded from the superior colliculus and classified into four types based on their responses, or lack of responses, during or preceding eye and head movements. Type 1 cells did not show changes in activity prior to gaze changes Type 2 cells were inhibited prior to and during eye movements. Cells discharging before normal saccadic eye movements (type 3) were found only in the rostral part of the colliculus. Cells discharging before head movements (type 4) were found only in the caudal part.

8. These results are discussed with respect to the production of gaze changes in the cat.
Metabolic mapping of neural pathways involved in gastrosecretory response to insulin hypoglycaemia in the rat
Authors: Kadekaro Massako , Savaki Helen , Sokoloff Louis
Published: December 2014

1. The central nervous structures involved in the gastrosecretory effect of insulin hypoglycaemia were investigated in twenty urethane‐anaesthetized rats, previously provided with a chronic gastric fistula, by means of the 2‐deoxy‐
D‐[14C]glucose autoradiographic technique.

2. Gastric secretion increased in animals in which plasma glucose concentration was reduced to a range of 84‐133 mg/100 ml. (mean ±
S.E. of mean, 94 ± 3) as compared to a range of 125‐215 mg/100 ml. (mean ±
S.E. of mean, 162 ± 8) in animals with normal gastric secretion.

3. In fourteen of nineteen structures examined the rate of glucose utilization remained constant over the range of plasma glucose concentrations of 84‐215 mg/100 ml. These structures included the ventromedial nucleus of the hypothalamus, the mamillary nuclei, the medial geniculate nuclei, globus pallidus, zona incerta, nucleus ambiguus, supraoptic nucleus, paraventricular nucleus, medial nucleus of the solitary tract, dorsal tegmental nucleus, red nucleus, inferior olivary nucleus, hippocampus and amygdaloid complex.

4. A significant inverse correlation between plasma glucose concentration and the rate of glucose consumption was found in the lateral nucleus of the solitary tract, dorsal nucleus of the vagus, perifornical area where fibres of the medial forebrain bundle course, the superior olivary nucleus and the interstitial nucleus of the stria terminalis.

5. Except for the superior olivary nucleus and the interstitial nucleus of the stria terminalis, all the structures affected by low plasma glucose concentration have previously been shown to participate in the gastrosecretory response to blockade of glucose utilization by pharmacological doses of 2‐deoxy‐
D‐glucose, indicating that these same nuclei are also activated by hypoglycaemia.
Proteins in cerebrospinal fluid and plasma of fetal sheep during development
Authors: Dziegielewska K. M. , Evans C. A. N. , Fossan G. , Lorscheider F. L. , Malinowska D. H. , Møllgård K. , Reynolds M. L. , Saunders N. R. , Wilkinson S.
Published: December 2014

1. The concentration of total protein in c.s.f. and plasma has been measured in fetal sheep of different gestational ages and in the adult. In c.s.f. it was highest (approximately 840 mg/100 ml.) in the youngest fetuses (35 days) and declined steeply by 60 days (260 mg/100 ml.). It decreased less markedly in the last half of gestation to reach about 50 mg/100 ml. at 125 days which is twice the adult value. Protein concentration in plasma was lowest in the youngest fetuses and did not rise much until the second half of gestation during which time it doubled. There was a further rather larger increase between the late fetal (125 days) stage and the adult.

2. Albumin, fetuin, α‐fetoprotein (AFP), transferrin and lipoprotein were identified in c.s.f. and plasma.

3. The concentrations of albumin, AFP and fetuin in c.s.f. and plasma at different gestational ages were measured using immunodiffusion and radioimmuno‐assays.

4. Albumin was the major protein in plasma at all ages studied (35‐128 days gestation and adult). Its concentration increased throughout gestation whereas that of fetuin was similar at all fetal ages and that of AFP declined markedly during the second half of gestation. In the adult, fetuin was only about 0·1% of the total protein in plasma and AFP was not detectable.

5. In 35‐40 day fetuses albumin, AFP and fetuin accounted for 90% of the total protein concentration in plasma and for about 70‐80% of the total protein concentration of c.s.f. As gestation progressed the concentration of all three proteins in c.s.f. declined. But the concentration of AFP and fetuin fell more rapidly and to a greater extent than that of albumin; neither AFP nor fetuin could be detected in adult c.s.f.

6. The c.s.f.: Plasma ratio was above 50% for AFP and above 60% for fetuin at 35 days compared with about 25% for albumin at the same fetal age. The c.s.f.: plasma ratios for all three proteins declined with increasing fetal age and were not significantly different from each other by about mid gestation.
Blood—cerebrospinal fluid transfer of plasma proteins during fetal development in the sheep
Authors: Dziegielewska K. M. , Evans C. A. N. , Malinowska D. H. , Møllgård K. , Reynolds M. L. , Saunders N. R.
Published: December 2014

1. The penetration of human and sheep plasma proteins from blood into c.s.f. of sheep fetuses (57‐86 days gestation) has been studied. The proteins were injected intravenously via cotyledonary vessels. After different time periods the c.s.f. concentrations of marker proteins were estimated by radioactive counting of iodinated human or sheep proteins or by immunoassay of human proteins.

2. Several proteins of similar molecular size penetrated into c.s.f. to a different extent in 60 day fetuses. The steady‐state c.s.f.: plasma ratios were about 15% for human AFP, 10% for human transferrin and sheep albumin, 7% for human α1‐antitrypsin, and 5% for human albumin. In older fetuses the penetration of protein from blood into c.s.f. was much reduced and no evidence for differential penetration of different proteins was found.

3. The penetration of human AFP, transferrin and sheep albumin from blood into c.s.f. was greater than can be accounted for by passive diffusion.

4. The results of this paper are discussed in relation to those of the preceding paper on the identification and quantification of proteins in fetal c.s.f. and plasma. The hypothesis is put forward that the choroid plexus of the immature (60 days and less) sheep fetus contains a mechanism for the transcellular transfer of plasma proteins which may be selective in nature and of importance for some aspects of brain development.
Discharges of Purkinje cells and mossy fibres in the cerebellar vermis of the monkey during saccadic eye movements and fixation
Authors: Kase Manabu , Miller David C. , Noda Hiroharu
Published: December 2014

1. Discharges of Purkinje cells and of presumed mossy fibres were extracellularly recorded from vermal lobules VI and VII of two monkeys during saccadic eye movements and fixation. Among the units showing changes in activity in relation to either saccades or eye position, eighty‐four units were identified as mossy fibres and ninety‐one units were Purkinje cells.

2. Based on the discharge patterns associated with saccades, mossy fibre units were classified into long‐lead burst, burst, and burst‐tonic units. The long‐lead burst units (twenty‐eight units) started firing long before the saccades, the discharge consisting of a prelude (average lead time: 160 msec) and a burst (average lead time: 16 msec). In twenty‐two units the saccade‐related bursts showed a directional preference. The burst units (thirty‐seven units) started firing slightly before the saccade onset (average lead time: 7·4 msec) and thirteen units showed directional preference. The bursts in burst‐tonic units (thirteen units) had an average lead time of 0·2 msec.

3. Among the ninety‐one Purkinje cells, eighty‐eight cells showed bursts associated with saccades. Three units paused for all directions of saccades.

4. Seventy‐one units out of the eighty‐eight burst Purkinje cells showed bursts beginning approximately at the saccade onset (average lead time: 0·6 msec) and lasting throughout the saccade. The durations of bursts and saccades were highly correlated (correlation coefficients ranging from 0·70 to 0·88).

5. In the remaining seventeen burst Purkinje cells, the bursts followed the saccade onset (average delay: 32 msec). The bursts started approximately 40 msec before the end of a saccade and persisted on the average 70 msec after its completion. Peak firing rate occurred with a close temporal relation to the end of the saccade.

6. The tonic activity in nineteen mossy fibres and five Purkinje cells changed with eye positions. In the nineteen mossy fibres, there were thirteen burst‐tonic and six tonic units. The activity in the five Purkinje cells was a linear function of horizontal eye position.