bluuebunny/crossref_metadata_2025 huggingface dataset:
Parabrachial area: electrophysiological evidence for an involvement in cold nociception
Authors: Menendez L. , Bester H. , Besson J. M. , Bernard J. F.
Published: December 2017

1. Thirty-five percent of 120 neurons recorded extracellularly in the parabrachial (PB) area of anesthetized rats responded to a peripheral cold stimulus (0 degrees C). The cold-sensitive neurons were located in the lateral PB area, and most of those exhibiting a strong response to cold stimuli were inside or in close vicinity to the area receiving a high density of projections from superficial neurons of the dorsal horn. 2. The receptive fields for cold stimulation often were restricted to one or two parts of the body with a contralateral predominance for the limbs. No side predominance was observed for the face. 3. From a low spontaneous activity (10th percentile < median < 90th percentile: 0.1 < 1.5 < 5 Hz), the PB neurons responded to cold noxious stimuli (0 degree C water bath or waterjet, 20 s), without observable delay, with a sustained discharge. The mean maximal response to the stimulus was 16.1 +/- 1.2 Hz (mean +/- SE; n = 42). 4. About one-half (45%) of these cold-sensitive neurons were activated specifically by cold stimulation and did not respond or were inhibited by noxious heat and/or pinch. The remaining (55%) cold-sensitive neurons were also driven by heat and/or pinch. 5. The cold-sensitive neurons exhibited a clear capacity to encode cold stimuli in the noxious range: the stimulus-response function was always positive and monotonic from 30 to 0 degrees C; the mean curve was linear between 20 and 0 degrees C before plateauing between 0 to -10 degrees C; the mean threshold to cold stimulation was 17.1 +/- 1 degrees C (n = 21) and the mean t50 was 10.7 +/- 1.1 degrees C (n = 13). 6. The cold-sensitive neurons responded to intense transcutaneous electrical stimulation with an early and/or a late peak of activation, the latencies of which were in the 15-50 ms and 80-170 ms ranges (n = 8), respectively, i.e., compatible with the activation of A delta and C fibers. Interestingly, the cold-specific neurons predominantly responded with a late peak, suggesting these neurons were primarily driven by peripheral C fibers. 7. The intravenous injection of morphine depressed the responses of PB neurons to cold noxious stimuli in a dose-related (1, 3, and 9 mg/kg) and naloxone reversible fashion. The ED50 value was estimated approximately 2 mg/kg. Furthermore, two populations of neurons could be separated according to their morphine sensitivity. 8. It is concluded that PB cold-nonspecific neurons could be involved in affective-emotional, autonomic and neuroendocrine reactions in response to noxious cold events. The PB cold-specific neurons could be, in addition, involved in some thermoregulatory processes.
Electrical filtering in gerbil isolated type I semicircular canal hair cells
Authors: Rennie K. J. , Ricci A. J. , Correia M. J.
Published: December 2017

1. Membrane potential responses of dissociated gerbil type I semicircular canal hair cells to current injections in whole cell current-clamp have been measured. The input resistance of type I cells was 21.4 +/- 14.3 (SD) M omega, (n = 25). Around the zero-current potential (Vz = -66.6 +/- 9.3 mV, n = 25), pulsed current injections (from approximately -200 to 750 pA) produced only small-amplitude, pulse-like changes in membrane potential. 2. Injecting constant current to hyperpolarize the membrane to around -100 mV resulted in a approximately 10-fold increase in membrane resistance. Current pulses superimposed on this constant hyperpolarization produced larger and more complex membrane potential changes. Depolarizing currents > or = 200 pA caused a rapid transient peak voltage before a plateau. 3. Membrane voltage was able to faithfully follow sine-wave current injections around Vz over the range 1-1,000 Hz with < 25% attenuation at 1 kHz. A previously described K conductance, IKI, which is active at Vz, produces the low input resistance and frequency response. This was confirmed by pharmacologically blocking IKI. This conductance, present in type I cells but not type II hair cells, would appear to confer on type I cells a lower gain, but a much broader bandwidth at Vz, than seen in type II cells.
Differential distribution of potassium channels in acutely demyelinated, primary-auditory neurons in vitro
Authors: Davis R. L.
Published: December 2017

1. Single-channel recordings of potassium channel activity were made from two populations of primary-auditory neurons maintained in tissue culture. The saccular nerve, which is the auditory component of the eighth cranial nerve in goldfish, was separated into two branches according to its peripheral innervation pattern. Neurons which innervated the rostral saccular macula corresponded to a class of cells that showed spike frequency adaptation; whereas, neurons which innervated the caudal macula were consistent with another type of cell that demonstrated bursting spontaneous firing patterns in vivo. Both somatic and internodal axonal membranes from each of these neuronal classes were studied after acute removal of the myelin sheath by microdissection. 2. Dye injections were used to discriminate neuronal from myelin membrane. After successful removal of the myelin, patch electrodes containing Lucifer yellow were used to fill a neuron and reveal its morphology within the myelin sheath. Patches on myelin led to filling of Schwann cells that surrounded the neuron. 3. Four kinds of potassium channels were observed and characterized according to unitary conductance, inactivation, and sensitivity to internal calcium. Three voltage-dependent K+ channel types were found on the somatic and axonal membrane of the two neuronal populations. Two channel types showed voltage-dependent inactivation and had average conductances of 32 and 19 pS, each with distinctive subconductance states. The third type of channel activity had an estimated conductance of 12 pS and was noninactivating. 4. The fourth type of channel was the Ca2(+)-activated K+ channel (k(Ca)), which was classified by the dependence of its activity on the calcium concentration at its cytoplasmic surface. Unlike the other three potassium channel types, this kind of channel was found exclusively on neurons that innervated the caudal sensory epithelium. As with the other kinds of potassium channels, it was found on both somatic and axonal internodal membranes.
H1-receptor-mediated excitation and facilitation of the heat response by histamine in canine visceral polymodal receptors studied in vitro
Authors: Koda H. , Minagawa M. , Si-Hong L. , Mizumura K. , Kumazawa T.
Published: December 2017

1. We examined excitation and the facilitatory effect on the heat responses induced by histamine in visceral polymodal receptors with the use of the canine testis-spermatic nerve preparation in vitro. 2. The proportion of units that showed excitation (> 10 impulses 1 min after application of histamine was initiated) increased roughly with higher concentrations of histamine: 7% at 1 microM, 26% at 10 microM, 79% at 100 microM, and 61% at 1,000 microM. The discharge rate also increased with the concentration. 3. Histamine (100 and 1,000 microM) responses > 0.5 imp/s were observed only in units with conduction velocities (CVs) of < or = 10 m/s, but not in those with CVs faster than 10 m/s. On average, histamine-induced discharges were significantly greater in units with CVs of < or = 10 m/s at all concentrations > or = 10 microM. Thus units studied in this experiment were empirically divided into slow-CV (< or = m/s) and fast-CV (> 10 m/s) groups. 4. Histamine significantly facilitated the heat responses of the slow-CV group from 10 microM, and also facilitated the fast-CV group from 100 microM. This sensitizing effect was observed irrespective of the precedent histamine-induced excitation. The magnitude of sensitization tended to increase with an increase in histamine concentration. 5. For studying the histamine receptor subtype involved in excitation and facilitation, we used D-chlorpheniramine maleate (5 microM) (an H1 receptor antagonist), famotidine (20 microM) (an H2 receptor antagonist), and thioperamide maleate (20 microM) (an H3 receptor antagonist). The magnitude of histamine-induced excitation of the slow-CV group was significantly suppressed by the H1 receptor antagonist but not by other antagonists. 6. The facilitatory effect of histamine on the heat response was also suppressed by the H1 receptor antagonist in both slow- and fast-CV groups. 7. These results strongly suggested that both excitation and facilitation of the heat response induced by histamine are mediated through the H1 receptor.
Two temporally overlapping "delayed-rectifiers" determine the voltage-dependent potassium current phenotype in cultured hippocampal interneurons
Authors: Chikwendu A. , McBain C. J.
Published: December 2017

1. Whole cell voltage-clamp recordings were used to characterize the calcium-independent "delayed-rectifier" potassium currents of gamma-aminobutyric acid (GABA)-positive stratum radiatum-lacunosum-moleculare (st. L-M) interneurons in primary culture derived from neonate rats [postnatal day 5-7 (P5-P7)]. 2. Two distinct current phenotypes were observed, which we termed "sustained" and "slowly inactivating." Despite possessing similar voltage-dependent activation properties, current differed in their time-dependent inactivation properties and their kinetics of activation and deactivation. The phenotypes of the observed currents did not change during the time in vitro. The total current phenotype observed in any cell likely resulted from the temporal overlap of the two current components expressed in different relative proportions. 3. Externally applied 4-aminopyridine (4-AP) selectively blocked the slowly inactivating current component, by a use-dependent, but voltage-independent mechanism, suggesting that channel activation is required for 4-AP to interact with its binding site. In contrast, the sustained current component was unaffected by 4-AP. 4. Both the slowly inactivating and sustained current phenotypes were sensitive to externally applied tetraethylammonium (TEA). The IC50 of block by TEA was lower in cells expressing predominantly the sustained current components. 5. Currents recorded in the presence of internally applied TEA were of a slowly inactivating phenotype, suggesting that [TEA]i preferentially blocked the sustained current component. 6. When test pulses were preceded by a prepulse to -100 mV, a transient A-type current component was observed, but in contrast to pyramidal neurons and other interneuron types, this transient current contributed only a minor component to the total initial peak current. 7. In conclusion, two distinct, temporally overlapping potassium current phenotypes were observed on st. L-M interneurons. The overall phenotype was determined by the relative proportion of each current component. The absence of a prominent transient current suggests that the two delayed-rectifier currents play a critical role in determining the firing characteristics of these interneurons.
Parapodial swim muscle in Aplysia brasiliana. II. Ca(2+)-dependent K+ currents in isolated muscle fibers and their blockade by chloride substitutes
Authors: Laurienti P. J. , Blankenship J. E.
Published: December 2017

1. We describe here the properties of two Ca(2+)-dependent K+ currents found in type II muscle fibers dissociated from the parapodia (swim appendages) of the marine snail Aplysia brasiliana. 2. Type II parapodial muscle fibers display three voltage-dependent currents that are also seen in type I fibers, a delayed rectifier current [IK(V)], a transient A current (IA), and a prominent L-type Ca2+ current. In addition, type II fibers also have two outward K+ currents, a transient, inactivating one and a slower, noninactivating one [IK(Ca,t) and IK(Ca,s), respectively], that are Ca2+ dependent. The expression of these currents in normal type II fibers generally produces a waveform of total outward current that is faster to peak than the total outward current seen in response to voltage steps in type I fibers and that does not inactivate at the end of an 80-ms voltage step. 3. Both IK(Ca,t) and IK(Ca,s) are absent when external Ca2+ is eliminated or when extracellular Ca2+ concentration ([Ca2+]o) is substituted with 10 mM Co2+ or Ba2+. Their threshold for activation is around -40 mV. IK(Ca,t) peaks rapidly and then inactivates, but IK(Ca,s) rises slowly and does not inactivate for as long as 200 ms. Both currents, like IK(V) and IA, are sensitive to tetraethylammonium and 4-aminopyridine and are not readily separated from either the voltage-gated currents or from one another by these pharmacological agents. 4. Tail current analysis from depolarized voltage steps in varying (K+]o demonstrates that these currents are carried by K+ ions and not by Cl-. 5. An unexpected finding, however, is that these Ca(2+)-dependent K+ currents are blocked by standard Cl- ion substitutes, such as methanesulfonate, isethionate, and propionate. IK(Ca,s) is slightly more sensitive to these Cl- substitutes than is IK(Ca,t). The chloride blocker 4,4'-diisothiocyantastilbene-2,2'disulfonic acid also partially blocked the Ca(2+)-dependent K+ currents. 6. The presence of these Ca(2+)-dependent K+ currents in type II fibers may contribute to a more rapid repolarization following depolarization-induced contractions. In contrast to type I fibers, which have smaller calcium current and no Ca(2+)-activated K+ currents, type II muscle cells may function more like "fast" fibers and relax more rapidly.
Presynaptic effects of a trinitrobenzene analogue at the frog neuromuscular junction
Authors: Osanai M. , Tsuji A. , Suzuki N. , Kijima H.
Published: December 2017

1. Application of 0.15 mM 1-(hydroxyethylamino)-2,4,6-trinitrobenzene (HEATNB) to the frog neuromuscular junction induced a marked increase (4.0-fold) in the amplitude of nerve-evoked end-plate potentials (EPPs) obtained from intracellular and extracellular records, but only a slight increase (1.9-fold) in the frequency of miniature EPPs (MEPPs) obtained from intracellular records. The effects of HEATNB on EPP amplitude and MEPP frequency showed a similar time course, reaching a plateau level approximately 40 min after the start of application and returning to the control level after wash. The difference in the effects of HEATNB on EPP and MEPP frequency suggests that it specifically enhances synchronous transmitter release. 2. Comparing the effects and structure of HEATNB with those of 2,4,6-trinitrobenzene-1-sulfonic acid, we conclude that the observed increase in transmitter release is due to the effects of the trinitrobenzene moiety of those reagents. 3. The distribution of MEPP amplitude was unchanged by HEATNB treatment, indicating that its effects are presynaptic. 4. Among four components of short-term synaptic plasticity, HEATNB greatly decreased (approximately 70%) augmentation and increased (approximately 50%) potentiation, but had little effect on fast and slow facilitations. These results suggest that each of the short-term plasticities has a different mechanism and that HEATNB affects the same mechanisms as those of augmentation. 5. Even when a calcium chelator, bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid, was loaded into the presynaptic nerve terminal, the effects of HEATNB were not changed in nature, suggesting that effects of HEATNB persist independently of intracellular Ca2+ concentration. 6. These observations suggest that HEATNB may affect specific protein(s) involved primarily in synchronous transmitter release and not asynchronous release.
Uniform growth and neuronal integration
Authors: Olsen O. , Nadim F. , Hill A. A. , Edwards D. H.
Published: December 2017

1. The cable equations were analyzed to determine the effects of two patterns of uniform growth on the passive and active integrative properties of neurons. 2. During uniform isoelectrotonic growth, the diameters of all neuronal processes increase as the square of their increase in length, while the specific electrical properties and branch terminal conditions of the neuron remain constant. An analytic inductive proof is given to show that, for any neuron, uniform isoelectrotonic growth increases the input conductance everywhere by the cube of the growth factor, but leaves the active and passive spread of membrane potential within the neuron unchanged. The spread of membrane voltage is unchanged because this pattern of growth enables both the axial and membrane currents everywhere in the cell to increase by the cube of the growth factor. Synaptic inputs would evoke the same responses in the isoelectrotonically larger cell as in the smaller cell if the total postsynaptic conductance of the synapse increased with the dendritic membrane area. 3. During uniform isometric growth, the diameter and lengths of all processes increase by the same factor, while the specific electrical properties and branch terminal conditions remain constant. This pattern of uniform growth increases the input conductance by the square of the growth factor, and also increases the attenuation, delay, and low-pass filtering of the cell's responses. Voltage attenuation increases with isometric growth because the axial current increases in proportion to growth, while the membrane current increases in proportion to the square of the growth factor. Isometric growth reduces the ability of distal synaptic inputs to affect the membrane potential at proximal integrating sites, even after the synaptic conductance has increased to compensate for the increased input conductance. 4. These two patterns of uniform growth help define the consequences of all types of uniform growth for neuronal integration and responsiveness.
Probability density estimation for the interpretation of neural population codes
Authors: Sanger T. D.
Published: December 2017

1. Electrophysiological recording data from multiple cells in motor cortex and elsewhere often are interpreted using the population vector method pioneered by Georgopoulos and coworkers. This paper proposes an alternative method for interpreting coding across populations of cells that may succeed under circumstances in which the population vector fails. 2. Population codes are analyzed using probability theory to find the complete conditional probability density of a movement parameter given the firing pattern of a set of cells. 3. The conditional probability density when a single cell fires is proportional to the shape of the cell's tuning curve of firing rate in response to different movement parameters. 4. The conditional density when multiple cells fire is proportional to the product of their tuning curves. 5. Movement parameters can be estimated from the conditional density using statistical maximum likelihood or minimum mean-squared error methods. 6. Simulations show that density estimation correctly finds movement directions for nonuniform distributions of preferred directions and noncosine cell tuning curves, whereas the population vector method fails for these cases. 7. Probability methods thus provide a statistically based alternative to the population vector for interpreting electrophysiological recording data from multiple cells.
Functional Magnetic Resonance Imaging Assessment of the Human Brain Auditory Cortex Response to Increasing Word Presentation Rates
Authors: Dhankhar Ajay , Wexler Bruce E. , Fulbright Robert K. , Halwes Terry , Blamire ANDREW M. , Shulman Robert G.
Published: December 2017

Dhankhar, Ajay, Bruce E. Wexler, Robert K. Fulbright, Terry Halwes, Andrew M. Blamire, and Robert G. Shulman. Functional magnetic resonance imaging assessment of the human brain auditory cortex response to increasing word presentation rates. J. Neurophysiol. 77: 476–483, 1997. In an investigation of the auditory cortex response to speech, six subjects were studied using echo-planar functional magnetic resonance imaging (fMRI) at 2.1T. The subjects were asked to listen to English nouns presented at various rates ranging from 0 words per minute (wpm) to 130 wpm while fMRI images encompassing their primary and posterior superior secondary auditory cortices were acquired. An asymmetric spin echo imaging sequence was used with an induced T2 weighting of 50 ms to allow for transverse relaxation effects. Images were acquired in two or four axial-oblique slices with a repetition time of 3.75 or 7.5 s, in plane resolution of 6 × 3 mm, and a slice thickness of 5 mm. Localized activation centered over grey matter was consistently observed in all subjects in the transverse temporal gyrus (TTG), the transverse temporal sulcus (TTS), and the posterior superior aspect of the superior temporal gyrus (STG). The total activated volume and the integrated signal response in bilateral primary and posterior superior secondary auditory cortices increased with increasing rate of word presentation, peaking at 90 wpm (with some intersubject variability) with a subsequent fall at 130 wpm. There were no significant differences in the rate dependence of the signal response in bilateral primary and bilateral posterior superior secondary auditory cortices ( P < 0.05).
Functionally Distinct Chloride-Mediated GABA Responses in Rat Cerebellar Granule Cells Cultured in a Low-Potassium Medium
Authors: Martina Marco , Virginio Caterina , Cherubini Enrico
Published: December 2017

Martina, Marco, Caterina Virginio, and Enrico Cherubini. Functionally distinct chloride-mediated GABA responses in rat cerebellar granule cells cultured in a low-potassium medium. J. Neurophysiol. 77: 507–510, 1997. The patch-clamp technique was used to study whole cell currents evoked by γ-aminobutyric acid (GABA) in rat cerebellar granule cells cultured in 5 mM potassium, a condition that favors the development of functionalGABAergic synapses. GABA activated both high- and low-sensitivity receptors. The high-sensitivity receptor had an effective concentration producing half the maximum response (EC50) of 13 μM, whereas the low-sensitivity one had an EC50 of 255 μM. TheGABAA receptor agonist isoguvacine activated only the high-sensitivity receptor with an EC50 of 16 μM. When GABA was applied during the desensitized phase of the response elicited by a saturating concentration of isoguvacine, it was still able to induce a small response, whereas when isoguvacine was applied during the desensitizing phase of GABA-evoked current no response was detected. GABA responses were highly heterogeneous regarding their sensitivity to bicuculline. In a small number of cells (3 of 25), bicuculline (10 μM) completely abolished GABA-evoked currents. In the majority of the neurons (22 of 25) the blocking effect of bicuculline (100 μM) was 64 ± 4% (mean ± SE). The bicuculline-resistant component was abolished by picrotoxin (100 μM). In bicuculline, the dose-response curve for GABA was fitted with a sigmoidal curve with an EC50 value of 209 μM. These data indicate that functional new GABA receptor types with unusual pharmacology could be switched on by conditions that maintain cells in their undifferentiated state.
Critical Period for the Monocular Deprivation Effect in Rats: Assessment With Sweep Visually Evoked Potentials
Authors: Guire Eric S. , Lickey Marvin E. , Gordon Barbara
Published: December 2017

Guire, Eric S., Marvin E. Lickey, and Barbara Gordon. Critical period for the monocular deprivation effect in rats: assessment with sweep visually evoked potentials. J. Neurophysiol. 81: 121–128, 1999. Rats and mice are the species most frequently used for cellular and biochemical studies of plasticity, but only a few studies have examined developmentally regulated visual plasticity in these species. Here we report a study of the critical period for monocular deprivation in Long-Evans rats in which visual pattern sweep evoked potentials (sweep VEP) was used. Successful recording of sweep VEPs depended on establishing a stable light plane of anesthesia. We found a mixture of halothane and NO2 to be suitable. During a single trial lasting 10 s, anesthetized rats ( n = 28) viewed a sinusoidal contrast grating (spatial frequency of 0.13 cycles/deg) that reversed phase at 3 Hz. During the trial, the grating contrast increased logarithmically from 1 to 70%. Extracellular recording pipettes were placed bilaterally in layers II/III of the binocular regions of primary visual cortex. Stimulating the right and left eye on alternate trials, sweep VEP amplitudes were collected for 30 trials from each eye. In monocularly deprived animals, the right eyelid had been sutured for 5 days before recording. Age at suture varied from P19 to P86. In 12 of 13 rats sutured between P19 and P50, the crossed response from the deprived eye was smaller than the crossed response from the nondeprived eye. The same relation prevailed for the uncrossed responses in 11 of 13 animals. There was no significant monocular deprivation effect in animals sutured between P55 and P86 ( n = 9). Dark rearing until approximately P90 followed by 5 days of eyelid suture resulted in a strong monocular deprivation effect in both crossed and uncrossed pathways ( n = 3). There was little effect of dark rearing alone on the size the sweep VEPs ( n = 3). The critical period reported here lasts at least 2 wk longer than reported for rats by Fagliolini et al. and for mice by Gordon and Stryker. Both previous studies used single unit recording rather than the sweep VEP method.
Eye Movement Deficits Following Ibotenic Acid Lesions of the Nucleus Prepositus Hypoglossi in Monkeys II. Pursuit, Vestibular, and Optokinetic Responses
Authors: Kaneko Chris R. S.
Published: December 2017

Eye movement deficits following ibotenic acid lesions of the nucleus prepositus hypoglossi in monkeys. II. Pursuit, vestibular, and optokinetic responses. The eyes are moved by a combination of neural commands that code eye velocity and eye position. The eye position signal is supposed to be derived from velocity-coded command signals by mathematical integration via a single oculomotor neural integrator. For horizontal eye movements, the neural integrator is thought to reside in the rostral nucleus prepositus hypoglossi (nph) and project directly to the abducens nuclei. In a previous study, permanent, serial ibotenic acid lesions of the nph in three rhesus macaques compromised the neural integrator for fixation but saccades were not affected. In the present study, to determine further whether the nph is the neural substrate for a single oculomotor neural integrator, the effects of those lesions on smooth pursuit, the vestibulo-ocular reflex (VOR), vestibular nystagmus (VN), and optokinetic nystagmus (OKN) are documented. The lesions were correlated with long-lasting deficits in eye movements, indicated most clearly by the animals’ inability to maintain steady gaze in the dark. However, smooth pursuit and sinusoidal VOR in the dark, like the saccades in the previous study, were affected minimally. The gain of horizontal smooth pursuit (eye movement/target movement) decreased slightly (<25%) and phase lead increased slightly for all frequencies (0.3–1.0 Hz, ±10° target tracking), most noticeably for higher frequencies (0.8–0.7 and ∼20° for 1.0-Hz tracking). Vertical smooth pursuit was not affected significantly. Surprisingly, horizontal sinusoidal VOR gain and phase also were not affected significantly. Lesions had complex effects on both VN and OKN. The plateau of per- and postrotatory VN was shortened substantially (∼50%), whereas the initial response and the time constant of decay decreased slightly. The initial OKN response also decreased slightly, and the charging phase was prolonged transiently then recovered to below normal levels like the VN time constant. Maximum steady-state, slow eye velocity of OKN decreased progressively by ∼30% over the course of the lesions. These results support the previous conclusion that the oculomotor neural integrator is not a single neural entity and that the mathematical integrative function for different oculomotor subsystems is most likely distributed among a number of nuclei. They also show that the nph apparently is not involved in integrating smooth pursuit signals and that lesions of the nph can fractionate the VOR and nystagmic responses to adequate stimuli.
Varying the Degree of Single-Whisker Stimulation Differentially Affects Phases of Intrinsic Signals in Rat Barrel Cortex
Authors: Polley Daniel B. , Chen-Bee Cynthia H. , Frostig Ron D.
Published: December 2017

Varying the degree of single-whisker stimulation differentially affects phases of intrinsic signals in rat barrel cortex. . Neurophysiol. 81: 692–701, 1999. Using intrinsic signal optical imaging (ISI), we have shown previously that the point spread of evoked activity in the rat barrel cortex in response to single-whisker stimulation encompasses a surprisingly large area. Given that our typical stimulation consists of five deflections at 5 Hz, the large area of evoked activity might have resulted from repetitive stimulation. Thus in the present study, we use ISI through the thinned skull to determine whether decreasing the degree of single-whisker stimulation decreases the area of the cortical point spread. We additionally outline a protocol to quantify stimulus-related differences in the temporal characteristics of intrinsic signals at a fine spatial scale. In 10 adult rats, whisker C2 was stimulated randomly with either one or five deflections delivered in a rostral-to-caudal fashion. Each deflection consisted of a 0.5-mm displacement of the whisker as measured at the point of contact, 15 mm from the snout. The number of whisker deflections did not affect the area or peak magnitude of the cortical point spread based on the intrinsic signal activity occurring from 0.5 up to 1.5 s poststimulus onset. In contrast, the magnitude and time course of intrinsic signal activity collected after 1.5-s poststimulus onset did reflect the difference in the degree of stimulation. Thus decreasing the degree of stimulation differentially affected the early and late phases of the evoked intrinsic signal response. The implications of the present results are discussed in respect to probable differences in the signal source underlying the early versus later phases of evoked intrinsic signals.
Light-Induced Calcium Influx Into Retinal Axons Is Regulated by Presynaptic Nicotinic Acetylcholine Receptor Activity In Vivo
Authors: Edwards James A. , Cline Hollis T.
Published: December 2017

Light-induced calcium influx into retinal axons is regulated by presynaptic nicotinic acetylcholine receptor activity in vivo. Visual activity is thought to be a critical factor in controlling the development of central retinal projections. Neuronal activity increases cytosolic calcium, which was hypothesized to regulate process outgrowth in neurons. We performed an in vivo imaging study in the retinotectal system of albino Xenopus laevis tadpoles with the fluorescent calcium indicator calcium green 1 dextran (CaGD) to test the role of calcium in regulating axon arbor development. We find that visual stimulus to the retina increased CaGD fluorescence intensity in retinal ganglion cell (RGC) axon arbors within the optic tectum and that branch additions to retinotectal axon arbors correlated with a local rise in calcium in the parent branch. We find three types of responses to visual stimulus, which roughly correlate with theon, off, and sustained response types of RGC reported by physiological criteria. Imaging in bandscan mode indicated that patterns of calcium transients were nonuniform throughout the axons. We tested whether the increase in calcium in the retinotectal axons required synaptic activity in the retina; intraocular application of tetrodotoxin (10 μM) or nifedipine (1 and 10 μM) blocked the stimulus-induced increase in RGC axonal fluorescence. A second series of pharmacological investigations was designed to determine the mechanism of the calcium elevation in the axon terminals within the optic tectum. Injection of bis-( o-aminophenoxy)- N, N, N′, N′-tetraacetic acid-AM (BAPTA-AM) (20 mM) into the tectal ventricle reduced axonal calcium levels, supporting the idea that visual stimulation increases axonal calcium. Injection of BAPTA (20 mM) into the tectal ventricle to chelate extracellular calcium also attenuated the calcium response to visual stimulation, indicating that calcium enters the axon from the extracellular medium. Caffeine (10 mM) caused a large increase in axonal calcium, indicating that intracellular stores contribute to the calcium signal. Presynaptic nicotinic acetylcholine receptors (nAChRs) may play a role in axon arbor development and the formation of the topographic retinotectal projection. Injection of nicotine (10 μM) into the tectal ventricle significantly elevated RGC axonal calcium levels, whereas application of the nAChR antagonist αBTX (100 nM) reduced the stimulus-evoked rise in RGC calcium fluorescence. These data suggest that light stimulus to the retina increases calcium in the axon terminal arbors through a mechanism that includes influx through nAChRs and amplification by calcium-induced calcium release from intracellular calcium stores. Such a mechanism may contribute to developmental plasticity of the retinotectal system by influencing both axon arbor elaboration and the strength of synaptic transmission.
The Mammalian Urinary Bladder: It's More Than Accommodating
Authors: Lewis Sk
Published: December 2017

Once tacitly assumed to be an inert sac, as evidenced by the lack of information in physiology textbooks, the mammalian urinary bladder epithelium is instead a dynamic system. We stress the structure-function relationship, which allows the bladder epithelium to accomodate large fluctuations in urine volume by orderly insertion and withdrawal of cytoplasmic vesicles. This process, coupled to a recently described hormonally regulated transport system, allows the bladder to maintain urine ionic composition nearly constant. In addition, studies on the bladder have revealed a novel regulatory system of ion transport involving channel degradation and turnover.
Inositol Lipid Metabolism and Intracellular Signaling Mechanisms
Authors: Williamson JR
Published: December 2017

Many hormones and neurotransmitters act by raising the intracellular level of free calcium in the target cells. The calcium is released from internal calcium stores, and this article discusses the links that exist between receptors in the cell membrane and the mobilization of calcium from these intracellular stores. Inositol lipids play a key role in these events.
New Paradigm: Sympathetic Neurotransmission by Lateral Interaction Between Secretory Units?
Authors: Stjarne L
Published: December 2017

Sympathetic transmitters are released from swellings (varicosities) on the terminal branches of sympathetic nerves. Do impulses in sympathetic nerve endings, as presently believed, always activate release of neurotransmitters from the varicosities? New techniques reveal that each varicosity mostly remains silent and responds only intermittently and infrequently to nerve impulses and that presently held views of sympathetic transmission need revision.
Jet Lag, Shift Work, and Maladaption
Authors: Moore-Ede MC
Published: December 2017

The circadian pacemakers, which time the approximately 24-h cycle of sleep and wakefulness, resynchronize only slowly after an abrupt phase shift in environmental time cues. Consequently, we are not well equipped to cope with jet travel across multiple time zones or with rotating shift work schedules, neither of which was in the evolutionary experience of the human species. Recent studies of the human circadian system suggest some strategies to minimize the ill effects of jet lag and shift work.
Problems of Expsoure to High Pressures
Authors: Brauer RW
Published: December 2017

Much physiological research has been concerned with responses to diving, which combines and blends the effect of pressure change as such with exposure to various gases at high pressure. Less attention has been given to the adaptation to pressure exposure over longer periods of time, and even less is known about organisms that live at abyssal depths of the ocean where pressure is in the order of 1,000 atmospheres.
Angiogenesis: What Makes Blood Vessels Grow?
Authors: Folkman J
Published: December 2017

The study of angiogenesis began almost two decades ago in an attempt to understand the role of vascularization in tumor growth. It is now a major field that includes the growth and regression of capillaries in embryological development, physiological functions, and pathological states. Both angiogenic peptides and angiostatic steroids serve in an elaborate control system of capillary growth, which in turn governs both growth and involution of tissues.
Does the Brain "Remember" the Absolute Blood Pressure?
Authors: Dorward PK , Korner PI
Published: December 2017

A sustained change in resting blood pressure causes the threshold of arterial baroreceptors to shift rapidly, within 20-30 s, in the same direction. This greatly enhances the compensation for disturbances that cause small to moderate changes in blood pressure. A corollary of rapid resetting is ambiguity about the absolute level of blood pressure. Arterial baroreceptor reflexes are good at responding to changes in blood pressure, but they do not provide good information about absolute pressure.
Endothelium and the Control of Vascular Tissue
Authors: Vanhoutte PM
Published: December 2017

Endothelial cells contribute more than an inside lining of blood vessels. They react to mechanical forces and to a number of substances, either locally produced or circulating in blood, that cause the release of one or more as yet unidentified endothelium-derived relaxing factors. Other agents, including stretch and blood pressure, evoke endothelium-dependent contraction of blood vessels. Such mechanisms make endothelial cells ideal sensors to monitor changes in the flow and composition of the blood.
How Are Inner Ear Fluids Formed?
Authors: Sterkers O , Ferrary E , Amiel C
Published: December 2017

The inner ear contains fluids that differ widely in composition and origin. The perilymph (in scala vestibuli and scala tympani) resembles a plasma ultrafiltrate, whereas the endolymph (in scala media) is a K+-rich fluid. The precursor of perilymph is blood plasma. The formation of endolymph proceeds from perilymph, is dependent on Na+-K+-ATPase activity, and also appears to involve a still unidentified electrogenic K+-transporting system.
The Chemical Transmission Mechanism of Excitation-Contraction Coupling in Skeletal Muscle
Authors: Vergara J , Asotra K
Published: December 2017

There is a temperature-dependent lag between depolarization of transverse tubules by the action potential and onset of calcium release from the sacromplasmic reticulum that reveals the occurrence of a chemical step in excitation-contraction coupling. Recent studies suggest that in vertebrate muscle inositol 1,4,5-trisphosphate may act as a chemical link in this process.
Nobel—The Award of the Prize
Authors: Schmidt-Nielsen Knut
Published: December 2017

October, the month in which this issue of NIPS is published, is also the month in which the names of the year's Nobel Laureates are revealed, followed by award ceremonies in December. The following account of this extraordinary event was written after the 1986 prize in physiology or medicine was awarded to Rita Levi-Montalcino and Stanley Cohen.
Regulation of Feeding by Neural Responses to Endogenous Factors
Authors: Oomura Y
Published: December 2017

Several recently identified metabolites have potent effects on food intake. They act in micromolar concentrations, and some suppress feeding, whereas others induce feeding. The neural networks involved in the integration of the signals from the chemosensitive neurons open new possibilities for understanding hunger and satiety.
Current Perspectives of Clara Cell Function
Authors: Van Scott MR , Boucher RC
Published: December 2017

Clara cells are the most common epithelial cells in the small airways of many mammals, but their function is for the most part still unknown. They are difficult to study in situ, but in culture they absorb Na+. If the Na+ is followed by a counterion and passive flow of water, the cells would function in fluid absorption. Thus fluid from the alveoli could be absorbed in the small airways, and the Clara cells could help keep the lungs dry.
Regulation of Sodium and Potassium in Muscles of Potassium-Deficient Rats
Authors: Akaike N
Published: December 2017

A K-deficient diet causes a decrease in plasma K in rats, but the cellular K concentration in brain tissue is maintained. In muscle tissue, however, the K concentration decreases, making it appear that the muscle serves as a buffer or reservoir for K. The decrease in muscle K is regulated from the hypothalamus, mediated by suppression of the muscle active Na-K pump. Interestingly, the control of tonic and twitch muscle differs.
Urine Concentration and the Length of the Renal Papilla
Authors: Greenwald L , Stetson D
Published: December 2017

Countercurrent multiplier theory predicts that the maximum urine concentration should be directly related to the length of the loop of Henle. However, those small rodents that achieve very high urine concentrations have much shorter loops than large mammals that produce far lower concentrations. To resolve this contradiction, we propose that the high mass-specific metabolic rates of small mammals make their kidneys capable of the intense active transport required to achieve high urine concentrations.
Laying Eggs at High Altitude
Authors: Monge CC , Leon-Velarde F , Gomez de la Torre G
Published: December 2017

The hypoxic and dry environment of the high mountains seems to select eggshells with porosities appropriate for the altitudinal level. At moderate altitudes, the conservation of water takes precedence over the oxygen-supply gradient. At very high altitudes there is a compromise between reducing water loss on the one hand and the defense of the oxygen supply to the embryo on the other.
Sculpturing New Muscle Phenotypes
Authors: Babij P , Booth FW
Published: December 2017

Changes in the pattern of muscle activity are followed by new patterns of protein synthesis, both in the contractile elements and in the enzymes of energy metabolism. Although the signal transducers have not been identified, techniques of molecular biology have clearly shown that the adaptive responses are the regulated consequence of differential gene expression.
Ultrasonic Analysis for Ocular Tumor Characterization and Therapy Assessment
Authors: Feleppa EJ , Lizzi FL , Coleman DJ
Published: December 2017

In ophthalmology, ultrasonic tissue characterization methods can distinguish among types of intraocular tumors, differentiate between subclasses of a given general type of tumor, provide parameters of use in treatment planning, and detect and grade changes in tissue during the course of therapy.
Unethical Alterations of Oxygen-Carrying Capacity in Endurance Athletes
Authors: Stray-Gundersen J
Published: December 2017

Some developments in the fields of physiology and medicine have had direct impact on athletic performance. These include the synthesis of anabolic steroids, the development of carbohydrate loading, the importance of adequate hydration, and the procedure of "blood doping." Most of these discoveries were made in the cours of attempting to understand basic physiology or treating patients and were not initially directed toward enhancing athletic performance The procedure of transfusing athletes is such a case.
The Axon Reflex: An Outdated Idea or a Valid Hypothesis?
Authors: Lisney SJW , Bharali LAM
Published: December 2017

Physiology textbooks almost always include the axon reflex in the context of the triple response, often followed by the caveat that the evidence is either indirect or incomplete. Experimental work and ideas on the topic are reviewed, asking whether there now is a stronger case for axon reflex mechanisms.
Control of Exocytosis in Single Cells
Authors: Maruyama Y
Published: December 2017

Exocytosis can be quantified by measuring changes in membrane capacitance in single internally perfused cells. Exocytosis is controlled by guanine nucleotide-binding proteins (G proteins) acting as key signal transducers. Different G proteins mediate receptor signaling and secretory granule-membrane fusion.
Airway Neuropeptides: Roles in Fine Tuning and In Disease?
Authors: Barnes PJ
Published: December 2017

Many neuropeptides have recently been identified in airways, with potent effects on airway caliber, blood flow, and secretions, raising the possibility that they are involved in airway diseases, such as asthma. Neuropeptides in sensory nerves induce inflammatory effects and may also contribute to the pathology of asthma. These findings may have important therapeutic implications.
Posthemorrhagic Syncope
Authors: Ludbrook J , Evans R
Published: December 2017

During acute blood loss, arterial pressure is at first maintained by widespread reflex vasoconstriction. Then, vasoconstriction fails abruptly and arterial pressure falls precipitately, despite massive vasopressin release. This decompensation can now be attributed to activation of an endogenous opioid mechanism in the brain by a signal from the heart.
Modulated Receptor Hypothesis: Selectivity and Interactions of Antiarrhythmic Drugs
Authors: Tamargo J , Valenzuela C , Delpon E
Published: December 2017

The modulated receptor hypothesis is useful in understanding the kinetics of Na+ channels and the changes produced by various antiarrhythmic drugs.
Mechanism of Ciliary Movement - What's New?
Authors: Satir P
Published: December 2017

The basic structure of cilia and flagella is highly conserved in eukaryotes from protozoa to humans, but the motions they perform may be strikingly different. Combined electron microscopic and biochemical studies have led to a unifying hypothesis about how movement is generated that may explain the different behaviors.
Volume Preservation: Then and Now
Authors: Schultz SG
Published: December 2017

Volume regulatory mechanisms, which evolved in Precambrian life and served to prevent cell lysis when our bacterial and invertebrate ancestors were confronted with hypotonic extracellular milieus, have been preserved in vertebrate cells but with redefined and highly sophisticated physiological functions.
The Number of Animals
Authors: McCance I
Published: December 2017

In deciding the number of animals required for an experiment the biologist must achieve a balance between several interacting and competing elements. Recent widespread legislative changes, directed to a wider scrutiny of this decision process, may affect that balance. The consequences are examined and shown to be potentially detrimental.
Gating Properties and Modulation of Na Channels
Authors: Nilius B
Published: December 2017

Na channels mediate a fast transfer of information in electrically excitable cells. The transition between open-closed transformations of the channel protein (gating) can be described by voltage-dependent transitions between at least four conformational states. Specialized regions within the channel molecule are involved in gating and pharmacological modulation.
The Aminophospholipid Translocase: A Transmembrane Lipid Pump - Physiological Significance
Authors: Devaus PF
Published: December 2017

Aminophospholipid translocase selectively pumps phosphatidylserine and phosphatidylethanolamine from the outer to the inner plasma membrane monolayer. The function of this translocase activity may be to establish and maintain lipid asymmetry and to trigger fluid-phase endocytosis in nucleated cells.
The Visual Guidance of Saccades and Fast Aiming Movements
Authors: Gielen CCAM , van Gisbergen JAM
Published: December 2017

Sensory signals are used to create an internal representation of the environment. There is good evidence that the same internal representation of target position in space is shared by different motor systems. A central problem is how the command signal is transformed from a spatial code at the sensory side into a dynamic activation signal appropriately matched to the properties of the effector system.
Calcium, Excitotoxins, and Brain Damage
Authors: Siesjo BK
Published: December 2017

Cellular energy failure and loss of calcium homeostasis are important mediators of ischemic brain damage. The role of influx/release has been reemphasized, and excitatory amino acids have been identified as mediators of enhanced calcium influx.