bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Lumbosacral Spinal Cord Interprets Loading During Stepping
Authors: Harkema Susan J. , Hurley Seanna L. , Patel Uday K. , Requejo Philip S. , Dobkin BRUCE H. , Edgerton V. Reggie
Published: December 2017

Harkema, Susan J., Seanna L. Hurley, Uday K. Patel, Philip S. Requejo, Bruce H. Dobkin, and V. Reggie Edgerton. Human lumbosacral spinal cord interprets loading during stepping. J. Neurophysiol. 77: 797–811, 1997. Studies suggest that the human lumbosacral spinal cord can generate steplike oscillating electromyographic (EMG) patterns, but it remains unclear to what degree these efferent patterns depend on the phasic peripheral sensory information associated with bilateral limb movements and loading. We examined the role of sensory information related to lower-extremity weight bearing in modulating the efferent motor patterns of spinal-cord-injured (SCI) subjects during manually assisted stepping on a treadmill. Four nonambulatory subjects, each with a chronic thoracic spinal cord injury, and two nondisabled subjects were studied. The level of loading, EMG patterns, and kinematics of the lower limbs were studied during manually assisted or unassisted stepping on a treadmill with body weight support. The relationships among lumbosacral motor pool activity [soleus (SOL), medial gastrocnemius (MG), and tibialis anterior (TA)], limb load, muscle-tendon length, and velocity of muscle-tendon length change were examined. The EMG mean amplitude of the SOL, MG, and TA was directly related to the peak load per step on the lower limb during locomotion. The effects on the EMG amplitude were qualitatively similar in subjects with normal, partial, or no detectable supraspinal input. Responses were most consistent in the SOL and MG at load levels of <50% of a subject's body weight. The modulation of the EMG amplitude from the SOL and MG, both across steps and within a step, was more closely associated with limb peak load than muscle-tendon stretch or the velocity of muscle-tendon stretch. Thus stretch reflexes were not the sole source of the phasic EMG activity in flexors and extensors during manually assisted stepping in SCI subjects. The EMG amplitude within a step was highly dependent on the phase of the step cycle regardless of level of load. These data suggest that level of loading on the lower limbs provides cues that enable the human lumbosacral spinal cord to modulate efferent output in a manner that may facilitate the generation of stepping. These data provide a rationale for gait rehabilitation strategies that utilize the level of load-bearing stepping to enhance the locomotor capability of SCI subjects.
Dorsal Horn Cells Connected to the Lissauer Tract and Their Relation to the Dorsal Root Potential in the Rat
Authors: Lidierth Malcolm , Wall Patrick D.
Published: December 2017

Lidierth, Malcolm and Patrick D. Wall. Dorsal horn cells connected to the Lissauer tract and their relation to the dorsal root potential in the rat. J. Neurophysiol. 80: 667–679, 1998. We have examined the role of dorsal horn cells that respond to Lissauer tract stimulation in regulating primary afferent depolarization (PAD). PAD was monitored by recording the dorsal root potential (DRP) in the roots of the lumbar cord. Recordings were made of the discharges of Lissauer tract-responsive cells, and their discharges were correlated with the DRPs occurring spontaneously and those evoked by stimulation. Electrical microstimulation of the Lissauer tract (<10 μA; 200 μs) was used to activate the tract selectively and evoke a characteristic long-latency DRP. Cells that were excited by Lissauer tract stimulation were found in the superficial laminae of the dorsal horn. They exhibited low rates of ongoing discharge and responded to Lissauer tract stimulation typically with a burst of impulses with a latency to onset of 5.6 ± 2.7 ms (mean ± SD) and to termination of 13.6 ± 4.1 ms ( n = 105). Lissauer tract-responsive cells in L5 were shown to receive convergent inputs from cutaneous and muscle afferents as they responded to stimulation of the sural nerve (100%, n = 19) and the nerve to gastrocnemius (95%, n = 19). The latency of the response to sural nerve stimulation was 3.7 ± 1.5 ms and to gastrocnemius nerve stimulation, 8.3 ± 3.6 ms. Stimulation through a microelectrode at a depth of 1.5 mm in the sensorimotor cortex (100 μA, 200 μs) evoked a response in 17 of 31 Lissauer tract-responsive cells (55%) with a latency to onset of 21.9 ± 2.8 ms ( n = 17). Stimulation of the sural nerve, nerve to gastrocnemius or sensorimotor cortex was shown to depress the response of Lissauer tract-responsive cells to a subsequent Lissauer tract stimulus. The ongoing discharges of Lissauer tract-responsive cells were correlated to the spontaneous DRP using spike-triggered averaging. Of 123 cells analyzed in this way, 117 (95%) were shown to be correlated to the DRP. In addition, the peaks of spontaneous negative DRPs in spinally transected animals were detected in software. Perievent time histograms triggered from these peaks showed the discharge of Lissauer tract-responsive cells to be correlated to the spontaneous DRPs in 57 of 62 cells (92%) recorded. We conclude that these data provide compelling evidence that the Lissauer tract, and the dorsal horn cells that it excites, mediate the PAD evoked from multiple neural pathways.
Tuning Bandwidths for Near-Threshold Stimuli in Area MT
Authors: Britten Kenneth H. , Newsome William T.
Published: December 2017

Britten, Kenneth H. and William T. Newsome. Tuning bandwidths for near-threshold stimuli in area MT. J. Neurophysiol. 80: 762–770, 1998. It is not known whether psychophysical performance depends primarily on small numbers of neurons optimally tuned to specific visual stimuli, or on larger populations of neurons that vary widely in their properties. Tuning bandwidths of single cells can provide important insight into this issue, yet most bandwidth measurements have been made using suprathreshold visual stimuli, whereas psychophysical measurements are frequently obtained near threshold. We therefore examined the directional tuning of cells in the middle temporal area (MT, or V5) using perithreshold, stochastic motion stimuli that we have employed extensively in combined psychophysical and physiological studies. The strength of the motion signal (coherence) in these displays can be varied independently of its direction. For each MT neuron, we characterized the directional bandwidth by fitting Gaussian functions to directional tuning data obtained at each of several motion coherences. Directional bandwidth increased modestly as the coherence of the stimulus was reduced. We then assessed the ability of MT neurons to discriminate opposed directions of motion along six equally spaced axes of motion spanning 180°. A signal detection analysis yielded neurometric functions for each axis of motion, from which neural thresholds could be extracted. Neural thresholds remained surprisingly low as the axis of motion diverged from the neuron's preferred-null axis, forming a plateau of high to medium sensitivity that extended ∼45° on either side of the preferred-null axis. We conclude that directional tuning remains broad in MT when motion signals are reduced to near-threshold values. Thus directional information is widely distributed in MT, even near the limits of psychophysical performance. These observations support models in which relatively large numbers of signals are pooled to inform psychophysical decisions.
Excitability of the Squid Giant Axon Revisited
Authors: Clay John R.
Published: December 2017

Clay, John R. Excitability of the squid giant axon revisited. J. Neurophysiol. 80: 903–913, 1998. The electrical properties of the giant axon from the common squid Loligo pealei have been reexamined. The primary motivation for this work was the observation that the refractoriness of the axon was significantly greater than the predictions of the standard model of nerve excitability. In particular, the axon fired only once in response to a sustained, suprathreshold stimulus. Similarly, only a single action potential was observed in response to the first pulse of a train of 1-ms duration current pulses, when the pulses were separated in time by ∼10 ms. The axon was refractory to all subsequent pulses in the train. The underlying mechanisms for these results concern both the sodium and potassium ion currents I Na and I K. Specifically, Na+ channel activation has long been known to be coupled to inactivation during a depolarizing voltage-clamp step. This feature appears to be required to simulate the pulse train results in a revised model of nerve excitability. Moreover, the activation curve for I K has a significantly steeper voltage dependence, especially near its threshold (approximately −60 mV), than in the standard model, which contributes to reduced excitability, and the fully activated current-voltage relation for I K has a nonlinear, rather than a linear, dependence on driving force. An additional aspect of the revised model is accumulation/depeletion of K+ in the space between the axon and the glial cells surrounding the axon, which is significant even during a single action potential and which can account for the 15–20 mV difference between the potassium equilibrium potential E K and the maximum afterhyperpolarization of the action potential. The modifications in I K can also account for the shape of voltage changes near the foot of the action potential.
Calcium-Dependent Spike-Frequency Accommodation in Hippocampal CA3 Nonpyramidal Neurons
Authors: Chitwood Raymond A. , Jaffe David B.
Published: December 2017

Chitwood, Raymond A. and David B. Jaffe. Calcium-dependent spike-frequency accommodation in hippocampal CA3 nonpyramidal neurons. J. Neurophysiol. 80: 983–988, 1998. Interneurons of the hippocampal formation are traditionally identified electrophysiologically as those cells that fire trains of weakly accommodating action potentials in response to depolarizing current injection. We studied the firing properties of nonpyramidal neurons in the five substrata of the CA3b region of hippocampus. With the use of whole cell recording methods we found that nonpyramidal neurons fired in a range from weak to strong spike-frequency accommodation (SFA) that was calcium dependent. Slow afterhyperpolarizations were not associated with strong SFA. In addition a subset of interneurons (∼20%) fired with an irregular firing pattern that was generally calcium independent. These results suggest a calcium-dependent mechanism for SFA in nonpyramidal neurons that is distinct from pyramidal cells and further demonstrates the heterogeneity of hippocampal interneurons.
Inhibition of a Hyperpolarization-Activated Current by Clonidine in Rat Dorsal Root Ganglion Neurons
Authors: Yagi Junichi , Sumino Rhyuji
Published: December 2017

Yagi, Junichi and Rhyuji Sumino. Inhibition of a hyperpolarization-activated current by clonidine in rat dorsal root ganglion neurons. J. Neurophysiol. 80: 1094–1104, 1998. Whole cell voltage- and current-clamp recordings were carried out to investigate the effects of clonidine, an α2-adrenoceptor agonist, in L4 and L5 dorsal root ganglion (DRG) neurons of the rat. In voltage-clamp mode, application of 20 μM clonidine reversibly reduced the inward current evoked by hyperpolarizing voltage steps. The “clonidine-sensitive current” was obtained by subtracting the current during clonidine application from the control current, and its properties were as follows. 1) It was a slowly activating inward current evoked by hyperpolarization. 2) The reversal potential in the standard extracellular solution ([K+]o = 5 mM, [Na+]o = 151 mM) was −38.3 mV, and reduction of [Na+]o shifted it to a more negative potential, whereas an increase of [K+]o shifted it to a more positive potential, indicating that the current was carried by Na+ and K+ ( P Na/ P K = 0.22). 3) The relationship between the chord conductance underlying the clonidine-sensitive current and voltage could be fitted by a Boltzmann equation. These results indicate that the clonidine-sensitive current corresponds to a hyperpolarization-activated current ( I h), i.e., clonidine inhibits I h in rat DRG neurons. DRG neurons were classified as small (15.9–32.9 μm diam), medium-sized (33–42.9 μm), and large (43–63.6 μm), and 7 of 19, 24 of 25, and 22 of 22 of these types exhibited I h with mean ± SE clonidine-induced inhibition values of 36.1 ± 3.5% ( n = 7), 43.1 ± 3.7% ( n = 24), and 35.1 ± 2.7% ( n = 22), respectively. Clonidine application to L4 and L5 DRG neurons excised from rats the sciatic nerves of which had been transected 14–35 days previously (transected DRG neurons) also reduced I h. In current-clamp mode, 9 of 13 intact and 4 of 6 transected medium-sized DRG neurons that exhibited I h responded to clonidine with hyperpolarization (>2 mV). Some medium-sized DRG neurons exhibited repetitive action potentials in response to a depolarizing current pulse, and clonidine reduced the firing discharge frequencies in 8 of 11 intact and 3 of 4 transected neurons tested. Injection of a hyperpolarizing current pulse produced time-dependent rectification in DRG neurons that exhibited I h, and clonidine blocked this rectification in all intact and transected neurons tested. These results suggest that inhibition of I h due to α2-adrenoceptor activation contributes to modulation of DRG neuronal activity in rats. On the basis of our findings, we discuss the possible mechanisms whereby sympathetically released norepinephrine modulates the abnormal activity of DRG neuronal cell bodies after nerve injury.
Functional MRI Study of Thalamic and Cortical Activations Evoked by Cutaneous Heat, Cold, and Tactile Stimuli
Authors: Davis Karen D. , Kwan Chun L. , Crawley Adrian P. , Mikulis David J.
Published: December 2017

Davis, Karen D., Chun L. Kwan, Adrian P. Crawley, and David J. Mikulis. Functional MRI study of thalamic and cortical activations evoked by cutaneous heat, cold, and tactile stimuli. J. Neurophysiol. 80: 1533–1546, 1998. Positron emission tomography studies have provided evidence for the involvement of the thalamus and cortex in pain and temperature perception. However, the involvement of these structures in pain and temperature perception of individual subjects has not been studied in detail with high spatial resolution imaging. As a first step toward this goal, we have used functional magnetic resonance imaging (fMRI) to locate discrete regions of the thalamus, insula, and second somatosensory cortex (S2) modulated during innocuous and noxious thermal stimulation. Results were compared with those obtained during tactile stimulation of the palm. High resolution functional images were acquired on a 1.5 T echospeed GE MR system with an in-plane resolution of 1.7 mm. A modified peltier-type thermal stimulator was used to deliver innocuous cool and warm and noxious cold and hot stimuli for 40–60 s to the thenar eminence of normal male and female volunteers. Experimental paradigms consisted of four repetitions of interleaved control and task stimuli. A pixel by pixel statistical analysis of images obtained during each task versus control (e.g., noxious heat vs. warm, warm vs. neutral temperature, etc.) was used to determine task-related activations. Painful thermal stimuli activated discrete regions within the lateral and medial thalamus, and insula, predominantly in the anterior insula in most subjects, and the contralateral S2 in 50% of subjects. The innocuous thermal stimuli did not activate the S2 in any of the subjects but activated the thalamus and posterior insula in 50% of subjects. By comparison, innocuous tactile stimulation consistently activated S2 bilaterally and the contralateral lateral thalamus. These data also demonstrate that noxious thermal and innocuous tactile-related activations overlap in S2. The data also suggest that innocuous and noxious-related activations may overlap within the thalamus but may be located in different regions of the insula. Therefore, we provide support for a role of the anterior insula, S2, and thalamus in the perception of pain; whereas the posterior insula appears to be involved in tactile and innocuous temperature perception. These data demonstrate the feasibility of using fMRI for studies of pain, temperature, and mechanical stimuli in individual subjects, even in small regions such as thalamic nuclei. However, the intersubject variability should be considered in future single subject imaging studies and studies that rely on averaged group responses.
Short-Term Plasticity in Hindlimb Motoneurons of Decerebrate Cats
Authors: Bennett David J. , Hultborn Hans , Fedirchuk Brent , Gorassini Monica
Published: December 2017

Bennett, David J., Hans Hultborn, Brent Fedirchuk, and Monica Gorassini. Short-term plasticity in hindlimb motoneurons of decerebrate cats. J. Neurophysiol. 80: 2038–2045, 1998. Cat hindlimb motoneurons possess noninactivating voltage-gated inward currents that can, under appropriate conditions, regeneratively produce sustained increments in depolarization and firing of the cell (i.e., plateau potentials). Recent studies in turtle dorsal horn neurons and motoneurons indicate that facilitation of plateaus occurs with repeated plateau activation (decreased threshold and increased duration; this phenomenon is referred to as warm-up). The purpose of the present study was to study warm-up in cat motoneurons. Initially, cells were studied by injecting a slow triangular current ramp intracellularly to determine the threshold for activation of the plateau. In cells where the sodium spikes were blocked with intracellular QX314, plateau activation was readily seen as a sudden jump in membrane potential, which was not directly reversed as the current was decreased (cf. hysteresis). With normal spiking, the plateau activation (the noninactivating inward current) was reflected by a steep and sustained jump in firing rate, which was not directly reversed as the current was decreased (hysteresis). Repetitive plateau activation significantly lowered the plateau activation threshold in 83% of cells (by on average 5 mV and 11 Hz with and without QX314, respectively). This interaction between successive plateaus (warm-up) occurred when tested with 3- to 6-s intervals; no interaction occurred at times >20 s. Plateaus initiated by synaptic activation from muscle stretch were also facilitated by repetition. Repeated slow muscle stretches that produced small phasic responses when a cell was hyperpolarized with intracellular current bias produced a larger and more prolonged responses (plateau) when the bias was removed, and the amplitude and duration of this response grew with repetition. The effects of warm-up seen with intracellular recordings during muscle stretch could also be recorded extracellularly with gross electromyographic (EMG) recordings. That is, the same repetitive stretch as above produced a progressively larger and more prolonged EMG response. Warm-up may be a functionally important form of short-term plasticity in motoneurons that secures efficient motor output once a threshold level is reached for a significant period. Finally, the finding that warm-up can be readily observed with gross EMG recordings will be useful in future studies of plateaus in awake animals and humans.
Attention Modulates Both Primary and Second Somatosensory Cortical Activities in Humans: A Magnetoencephalographic Study
Authors: Mima Tatsuya , Nagamine Takashi , Nakamura Kaori , Shibasaki Hiroshi
Published: December 2017

Mima, Tatsuya, Takashi Nagamine, Kaori Nakamura, and Hiroshi Shibasaki. Attention modulates both primary and second somatosensory cortical activities in humans: a magnetoencephalographic study. J. Neurophysiol. 80: 2215–2221, 1998. To clarify the role of primary and second somatosensory cortex (SI and SII) in somatosensory discrimination, we recorded somatosensory evoked magnetic fields during a stimulus strength discrimination task. The temporal pattern of cortical activation was analyzed by dipole source model coregistered with magnetic resonance image. Stimulus intensity was represented in SI as early as 20 ms after the stimulus presentation. The later components of SI response (latency 37.7 and 67.9 ms) were enhanced by rarely presented stimuli (stimulus deviancy) during passive and active attention. This supports an early haptic memory mechanism in human primary sensory cortex. Contra- and ipsilateral SII responses followed the SI responses (latency 124.6 and 138.3 ms, respectively) and were enhanced by attention more prominently than the SI responses. Active attention increased SII but not SI activity. These results are consistent with the concept of ventral somatosensory pathway that SI and SII are hierarchically organized for passive and active detection of discrete stimuli.
Hypothesis for Shared Central Processing of Canal and Otolith Signals
Authors: Green Andrea M. , Galiana Henrietta L.
Published: December 2017

Green, Andrea M. and Henrietta L. Galiana. Hypothesis for shared central processing of canal and otolith signals. J. Neurophysiol. 80: 2222–2228, 1998. A common goal of the translational vestibuloocular reflex (TVOR) and the rotational vestibuloocular reflex (RVOR) is to stabilize visual targets on the retinae during head movement. However, these reflexes differ significantly in their dynamic characteristics at both sensory and motor levels, implying a requirement for different central processing of canal and otolith signals. Semicircular canal afferents carry a signal proportional to angular head velocity, whereas primary otolith afferents modulate approximately in phase with linear head acceleration. Behaviorally, the RVOR exhibits a robust response down to ∼0.01 Hz, yet the TVOR is only significant above ∼0.5 Hz. Several hypotheses were proposed to address central processing in the TVOR pathways. All rely on a central filtering process that precedes a “neural integrator” shared with the RVOR. We propose an alternative hypothesis for the convergence of canal and otolith signals that does not impose the requirement for additional low-pass filters for the TVOR. The approach is demonstrated using an anatomically based, simple model structure that reproduces the general dynamic characteristics of the RVOR and TVOR at both ocular and central levels. Differential dynamic processing of otolith and canal signals is achieved by virtue of the location at which sensory information enters a shared but distributed neural integrator. As a result, only the RVOR is provided with compensation for the eye plant. Hence canal and otolith signals share a common central integrator, as in previous hypotheses. However, we propose that the required additional filtering of otolith signals is provided by the eye plant.
Voltage-Activated K+ Currents of Hypoglossal Motoneurons in a Brain Stem Slice Preparation From the Neonatal Rat
Authors: Lape Remigijus , Nistri Andrea
Published: December 2017

Lape, Remigijus and Andrea Nistri. Voltage-activated K+ currents of hypoglossal motoneurons in a brain stem slice preparation from the neonatal rat. J. Neurophysiol. 81: 140–148, 1999. Whole cell, patch-clamp recordings were performed on motoneurons of the hypoglossus nucleus in a brain stem slice preparation from the neonatal rat brain. The aim was to investigate transient outward currents activated by membrane depolarization under voltage clamp conditions. In a Ca2+-free medium containing tetrodotoxin and Cs+, depolarizing voltage commands from a holding potential of −50 mV induced slow outward currents ( I slow) with 34 ± 6 ms (SE) onset time constant at 0 mV and minimal decline during a 1 s pulse depolarization. When the depolarizing command was preceded by a prepulse to −110 mV, the outward current became biphasic as it comprised a faster component ( I fast), which could be investigated in isolation by subtracting the two sets of records. I fast showed rapid kinetics (9 ± 4 ms 10–90% rise time and 70 ± 20 ms decay time constant at 0 mV) and strong voltage-dependent inactivation (half inactivation was at −92.9 ± 0.2 mV) from which it readily recovered with a biexponential timecourse (4.4 ± 0.6 and 17 ± 2 ms time constants at −110 mV membrane potential). I slow was selectively blocked by TEA (10–30 mM) while I fast was preferentially depressed by 2–3 mM 4-aminopyridine. Analysis of tail current reversal indicated that both I slow and I fast were predominantly due to K+ with minor permeability to Na+ (92/1 and 50/1, respectively). These results suggest that membrane depolarization activated distinct K+ conductances that, in view of their largely dissimilar kinetics, are likely to play a differential role in regulating the firing behavior of hypoglossal motoneurons.
Step-Tracking Movements of the Wrist. IV. Muscle Activity Associated With Movements in Different Directions
Authors: Hoffman Donna S. , Strick Peter L.
Published: December 2017

Hoffman, Donna S. and Peter L. Strick. Step-tracking movements of the wrist. IV. Muscle activity associated with movements in different directions. J. Neurophysiol. 81: 319–333, 1999. We examined the patterns of muscle activity associated with multiple directions of step-tracking movements of the wrist in humans and monkeys. Human subjects made wrist movements to 12 different targets that required varying amounts of flexion-extension and radial-ulnar deviation. Wrist muscles displayed two patterns of electromyographic (EMG) modulation as movement direction changed: amplitude graded and temporally shifted. The amplitude-graded pattern was characterized by modulation of the quantity of muscle activity that occurred during two distinct time periods, an agonist burst interval that began before movement onset and an antagonist burst interval that began just after movement onset. The timing of muscle activity over the two intervals showed little variation with changes in movement direction. For some directions of movement, EMG activity was present over both time intervals, resulting in “double bursts.” Modulation of activity during the agonist burst interval was particularly systematic and was well fit by a cosine function. In contrast, the temporally shifted pattern was characterized by a gradual change in the timing of a single burst of muscle activity. The burst occurred at a time intermediate between the agonist and antagonist burst intervals. The temporally shifted pattern was seen less frequently than the amplitude-graded pattern and was present only in selected wrist muscles for specific directions of movement. Monkeys made wrist movements to 8–16 different targets that required varying amounts of flexion-extension and radial-ulnar deviation. These movements were performed more slowly than those of human subjects. The wrist muscles of the monkeys we examined displayed the amplitude-graded pattern of activity but not the temporally shifted pattern. Stimulation of individual wrist muscles in monkeys resulted in wrist movements that were markedly curved, particularly for the wrist extensors. These results indicate that step-tracking movements of the wrist are generated mainly by using the amplitude-graded pattern to modulate muscle activity. We propose that this pattern reflects a central process that decomposes an intended movement into an agonist, “propulsive” component and an antagonist, “braking” component. Separate bursts of muscle activity then are generated to control each component. On the other hand, we argue that the temporally shifted pattern may function to reduce the amount of movement curvature associated with the activation of wrist muscles.
Cannabinoid Suppression of Noxious Heat-Evoked Activity in Wide Dynamic Range Neurons in the Lumbar Dorsal Horn of the Rat
Authors: Hohmann Andrea G. , Tsou Kang , Walker J. Michael
Published: December 2017

Cannabinoid suppression of noxious heat-evoked activity in wide dynamic range neurons in the lumbar dorsal horn of the rat. The effects of cannabinoid agonists on noxious heat-evoked firing of 62 spinal wide dynamic range (WDR) neurons were examined in urethan-anesthetized rats (1 cell/animal). Noxious thermal stimulation was applied with a Peltier device to the receptive fields in the ipsilateral hindpaw of isolated WDR neurons. To assess the site of action, cannabinoids were administered systemically in intact and spinally transected rats and intraventricularly. Both the aminoalkylindole cannabinoid WIN55,212-2 (125 μg/kg iv) and the bicyclic cannabinoid CP55,940 (125 μg/kg iv) suppressed noxious heat-evoked activity. Responses evoked by mild pressure in nonnociceptive neurons were not altered by CP55,940 (125 μg/kg iv), consistent with previous observations with another cannabinoid agonist, WIN55,212-2. The cannabinoid induced-suppression of noxious heat-evoked activity was blocked by pretreatment with SR141716A (1 mg/kg iv), a competitive antagonist for central cannabinoid CB1 receptors. By contrast, intravenous administration of either vehicle or the receptor-inactive enantiomer WIN55,212-3 (125 μg/kg) failed to alter noxious heat-evoked activity. The suppression of noxious heat-evoked activity induced by WIN55,212-2 in the lumbar dorsal horn of intact animals was markedly attenuated in spinal rats. Moreover, intraventricular administration of WIN55,212-2 suppressed noxious heat-evoked activity in spinal WDR neurons. By contrast, both vehicle and enantiomer were inactive. These findings suggest that cannabinoids selectively modulate the activity of nociceptive neurons in the spinal dorsal horn by actions at CB1 receptors. This modulation represents a suppression of pain neurotransmission because the inhibitory effects are selective for pain-sensitive neurons and are observed with different modalities of noxious stimulation. The data also provide converging lines of evidence for a role for descending antinociceptive mechanisms in cannabinoid modulation of spinal nociceptive processing.
Contribution of Sensory Feedback to the Generation of Extensor Activity During Walking in the Decerebrate Cat
Authors: Hiebert Gordon W. , Pearson Keir G.
Published: December 2017

Contribution of sensory feedback to the generation of extensor activity during walking in the decerebrate cat. In this investigation we have estimated the afferent contribution to the generation of activity in the knee and ankle extensor muscles during walking in decerebrate cats by loading and unloading extensor muscles, and by unilateral deafferentation of a hind leg. The total contribution of afferent feedback to extensor burst generation was estimated by allowing one hind leg to step into a hole in the treadmill belt on which the animal was walking. In the absence of ground support the level of activity in knee and ankle extensor muscles was reduced to ∼70% of normal. Activity in the ankle extensors could be restored during the “foot-in-hole” trials by selectively resisting extension at the ankle. Thus feedback from proprioceptors in the ankle extensor muscles probably makes a large contribution to burst generation in these muscles during weight-bearing steps. Similarly, feedback from proprioceptors in knee extensor appears to contribute substantially to the activation of knee extensor muscles because unloading and loading these muscles, by lifting and dropping the hindquarters, strongly reduced and increased, respectively, the level of activity in the knee extensors. This conclusion was supported by the finding that partial deafferentation of one hind leg by transection of the L4–L6 dorsal roots reduced the level of activity in the knee extensors by ∼50%, but did not noticeably influence the activity in ankle extensor muscles. However, extending the deafferentation to include the L7–S2dorsal roots decreased the ankle extensor activity. We conclude that afferent feedback contributes to more than one-half of the input to knee and ankle extensor motoneurons during the stance phase of walking in decerebrate cats. The continuous contribution of afferent feedback to the generation of extensor activity could function to automatically adjust the intensity of activity to meet external demands.
Ephaptic Interactions: A Significant mode of Communications in the Brain
Authors: Krnjevic K
Published: December 2017

Though first postulated many decades ago, the functional significance of electric (ephaptic) interactions between neighboring nerve cells has been largely ignored. Instead, attention has been focused on chemical transmission as the generally accepted mode of cell-to-cell communication in the brain. In recent years, however, clear inhibitory or excitatory ephaptic interactions have been demonstrated in certain regions of the brain, notably in the hippocampus. Such interactions may greatly enhance synchronized firing of pyramidal cells in seizure discharges.
Digestive Physiology in Primates
Authors: Milton K
Published: December 2017

Most primates are nearly or exclusively herbivores, but their digestive tract does not show the high degree of morphological specialization seen in many other herbivores. Even some of the smallest primates, which until recently were believed to be carnivorous, subsist on plant food. In humans the large intestine is relatively less voluminous than in apes (which are predominently plant eaters), but nevertheless, humans are surprisingly effective at digesting food cellulose.
Central Neurotransmitter Pathways for Baroreceptor-Initiated Secretion of Vasopressin
Authors: Blessing WW
Published: December 2017

Secretion of vasopressin in response to hemorrhage depends on the functional integrity of noradrenaline- and neuropeptide Y-containing neurons. The effects of microinjections of neuropharmacological agents have clarified the role of these neurons, which project directly from the caudal ventrolateral medulla oblongata to the neuroendocrine cells in the hypothalamus.
The Lungs During Exercise
Authors: Wagner PD
Published: December 2017

Lung function in humans during exercise has usually been regarded as well maintained, or even improved, compared with rest. Recent data, however, document considerable gas exchange inefficiency during very heavy work by well-trained normal subjects, and even more so when world-class athletes exercise maximally. Ascent to altitude clearly accentuates these problems. The deterioration of gas exchange seems to be caused mostly by failure of equilibration by diffusion of oxygen between alveolar gas and end-capillary blood.
A Hypothalamic Pulse Generator Governs Mammalian Reproduction
Authors: Knobil E
Published: December 2017

The hypothalamus of mammals contains an oscillator or pulse generator that in the unmodulated state has a period of approximately one hour in monkeys and humans. The activation of this system initiates a cascade of neuroendocrine events that are required for normal gonadal function in both sexes. Deviation from the physiological frequency of the pulse generator leads to profound disturbances of the reproductive process.
Erythropoietin Production in the Kidney
Authors: Bauer C , Kurtz A
Published: December 2017

The hormone erythropoietin stimulates erythrocyte production and therefore regulates the oxygen capacity of the blood. Hypoxia promotes erythropoietin formation by stimulating the transcription of the erythropoietin gene in the kidney and, to a lesser extent, in the liver. Chemical signals involved in the activation of the erythropoietin gene seem to be prostaglandins and cyclic AMP. The cells that serve as oxygen sensors may be mesangial cells of the glomerulus;in culture these cells release erythropoietin when oxygen tension is lowered.
Mammary Cultures on Floating Gels: A Model System for Mammary Function
Authors: Neville MC
Published: December 2017

Cultures of mammary epithelium on collagen gels can be induced to secrete the normal complement of milk proteins if the gels are released from the culture dish, allowing them to contract. During the contraction the epithelial cells undergo a shape change from flattened to columnar that initiates secretion of milk proteins. These floating cultures are dependent on hormones and offer a valuable model system for the study of milk secretion and its regulation.
Periodic Signaling as an Optimal Mode of Intercellular Communication
Authors: Goldbeter A
Published: December 2017

Many hormones must be delivered in a periodic, pulsatile manner to exert their physiological effect. Similarly, periodic pulses of cyclic AMP control the development of the amebae of the slime mold Dictyostelium discoideum, a system that provides insight into the function of pulsatile patterns of hormone secretion. In both instances, periodic signaling represents an optimal mode of intercellular communication that allows for maximum responsiveness where constant stimuli bring desensitization.
What are the Roles of Interferons in Physiological Conditions?
Authors: Bocci V
Published: December 2017

Interferon was discovered in 1957 as a natural antiviral substance. Since then other interferons have been described, and their antiproliferative and immunomodulatory effects are now being exploited in clinics. However, interferons as well as other cytokines are also produced in physiological conditions at particular sites. The efficiency of the immune system in preserving homeostasis and allowing survival depends, at least in part, on this continuous response.
How Do Vascular Endothelial Cells Respond to Flow?
Authors: Davies PF
Published: December 2017

Endothelial cells lining the circulation are continuously subjected to hemodynamic forces. Because flow is known to influence constriction and relaxation of small arteries and is implicated in the localization of athherosclerotic lesions in large arteries, the role of the endothelium as a "mechanotransducer" of flow-related forces, particularly shear stresses, is of great interest.
Cardiopulmonary-Arterial Baroreceptor Interaction in Control of Blood Pressure
Authors: Persson PB , Ehmke H , Kirchheim Hartmut R
Published: December 2017

Arterial baroreceptors effectively buffer short-term pressure changes. However, their importance for long-term pressure control appears to be minor. In contrast, cardiopulmonary reflexes cannot sense short-term fluctuations in arterial pressure but may be involved in the long-term regulation. Knowledge of the interaction of both receptor areas may enhance our understanding of blood pressure regulation.
The Radiation Inactivation of Membrane Transport Systems
Authors: Beliveau R , Potier M
Published: December 2017

Relatively few methods are available to estimate the size of proteins in biological membranes. The radiation inactivation method does not require purified preparation and allows the study in situ of physical interaction between protein subunits, providing crucial information about the structure-function relationship of protein molecules.
The Cellular Basis of Endothermic Metabolism: A Role for "Leaky" Membranes?
Authors: Hulbert AJ , Else PL
Published: December 2017

The high metabolic rate of endotherms is largely a cellular characteristic as reflected by tissue mitochondrial parameters. The cells of endotherms appear to be considerably "leakier" to Na+ and K+ than those of ectothermic animals. Tissue metabolic rate is correlated with the "leakiness" of the cell membranes.
Pregnancy Sickness
Authors: Andrews P , Whitehead S
Published: December 2017

The majority of women suffer from nausea and vomiting in the first trimester of pregnancy, but the mechanisms and reasons for this are unknown. Based on our current understanding of the emetic response and physiological changes of early pregnancy, hypotheses are put forward to explain this apparently inappropriate response to conception.
Medullipin System of Blood Pressure Control
Authors: Muirhead EE
Published: December 2017

Renomedullary interstitial cells of renal papilla secrete medullipin I, which is conveyed to the liver and converted to medullipin II, a vasodilator that suppresses sympathetic tone, causes diuresis-natriuresis, and has a suppressive effect on the central nervous system. These are opposite effects to those of renin-angiotensin.
Melatonin: That Ubiquitously Acting Pineal Hormone
Authors: Reiter RJ
Published: December 2017

Circadian production and secretion of melatonin from mammalian pineal gland provides animals with information concerning the light/dark environment. Melatonin passes easily through cell membranes;thus each organ, provided it can interpret the melatonin message, can adjust its physiological activity accordingly.
Endothelial Dysfunction in Shock States
Authors: Kovach AGB , Lefer AM
Published: December 2017

Circulatory shock results in dysfunction of the endothelium in various vascular beds. This dysfunction is characterized by marked impairment in the vasculature's ability to relax to endothelium-dependent vasodilators. This loss of endothelium-derived relaxing factor, or nitric oxide, leads to profound tissue injury.
Acetylcholinesterase and Neural Development: New Tricks for an Old Dog?
Authors: Robertson RT , Yu J
Published: December 2017

Patterns of intense acetylcholinesterase activity occur transiently in developing thalamocortical projection neurons and their terminal fields in sensory regions of cerebral cortex. These patterns correlate well with the time of ingrowth of thalamocortical axons and synaptogenesis with cortical neurons.
Extracellular Matrix: The Cellular Environment
Authors: Scott-Burden T
Published: December 2017

The extracellular matrix consists of a mixture of macromolecules that is specific for any given tissue and makes up a distinct environment for the different cells of the body. The study of these macromolecules and their assembly into complex extracellular matrix structures has focused attention on their physiological importance.
Breathing Rhythm Generation: Focus on the Rostral Ventrolateral Medulla
Authors: Duffin J , Ezure K , Lipski J
Published: December 2017

Current knowledge about the generation of breathing rhythm is reviewed. The respiratory neurophysiology of the medulla and particularly its rostral ventrolateral part as well as the major hypotheses of breathing rhythm generation are discussed. A model incorporating recent concepts is presented.
A Brain Stem Reflex in the Blink of an Eye
Authors: Evinger C
Published: December 2017

The mammalian eyelid participates in blinking and eye movements. Blinking requires transient lid movements, whereas the lid movements accompanying eye movements additionally involve maintaining the lid in a new position. Eyelid control evolved so that the lid-closing muscle governs blinks and the lid-opening muscle determines lid position.
Graded Ischemia in Exercising Human Skeletal Muscles: Methods and Applications
Authors: Bjurstedt H , Eiken O
Published: December 2017

A method was developed for inducing graded blood flow restriction in exercising large muscle groups in humans. The method holds promise as a means to study local and systemic effects of ischemic exercise. Recent applications include studies on the effects of long-term leg ischemia in endurance training.
Skeletal Muscle Vasculature and Systemic Hypoxia
Authors: Marshall JM
Published: December 2017

Studies involving recordings of gross muscle blood flow and intravital microscopy have been used to analyze the behavior of muscle vasculature during systemic hypoxia. The roles of sympathetic nerve activity, circulating hormones (e.g., catecholamines, angiotensin, vasopressin), and locally released adenosine and K+ in determining the behavior of arterial and venous vessels are considered.
Neuronal Inhibition Determines the Gastrointestinal Motor State
Authors: Delbro DS
Published: December 2017

The nerve-blocking agent tetrodotoxin induces contractile activity of the gut circular muscle, in vitro, and intestinal hypermotility, in vivo. According to an hypothesis put forward more than 20 years ago, the circular muscle layer is tonically suppressed due to spontaneously active myenteric neurons that "drive" inhibitory motoneurons to the muscle.
Stress, Arousal, and Gene Activation at Birth
Authors: Lagercrantz H
Published: December 2017

The fetus is adapted to a low O2 level with a number of functions inhibited. During delivery, the catecholamines and other stress hormones surge. In the brain of the newborn rat, increased norepinephrine turnover and expression of c-fos have been demonstrated. These findings might explain the arousal and alertness of the newborn infant.
Amiloride-Sensitive Na+ Channels: Insights and Outlooks
Authors: Benos DJ , Fuller CM , Shlyonsky VG , Berdiev BK , Ismailov I
Published: December 2017

Amiloride-sensitive Na+ channels are important control elements used in regulating Na+ transport into cells and across epithelia. These channels are widespread and display a myriad of different properties. Even a single type of amiloride-sensitive Na+ channels can have variable characteristics, depending on its biochemical and/or physical configuration.
Regulation of Ion Transport in Colonic Crypts
Authors: Greger R , Bleich M , Leipziger J , Ecke D , Mall M , Kunzelmann K
Published: December 2017

Colonic crypt cells, depending on regulatory influences such as neurotransmitters and hormones, can absorb or secrete NaCl. The large changes in absolute rates of transport, multiplicity of regulatory pathways, and complete reversal of vectorial transport in these cells pose intriguing questions. Some of these questions have been examined recently;most answers came as a complete surprise.
Cholecystokinin Type A and Type B Receptors and Their Modulation of Opioid Analgesia
Authors: Benedetti F
Published: December 2017

Several lines of evidence indicate that cholecystokinin (CCK) antagonists potentiate analgesia induced by exogenous opioids. Similarly, CCK antagonists enhance analgesia induced by procedures that activate endogenous opioid systems. However, because there are substantial species differences in receptor specificity and distribution, the role of CCK type A and type B receptors has yet to be clearly established.
Mechanical Links Between Locomotion and Breathing: Can You Breathe With Your Legs?
Authors: Lee H-t , Banzett RB
Published: December 2017

Mechanical links between locomotion and respiration are inherently appealing because they may lower the cost of respiration, but they may also limit the ability to adapt ventilation appropriately to physiological needs. Although correlative evidence supports several linkage mechanisms, mechanical links contribute <20% of the tidal volume in exercising animals.
Antistress Pattern Induced by Oxytocin
Authors: Uvnäs-Moberg Kerstin
Published: December 2017

Repeated oxytocin injections cause lowered blood pressure, decreased cortisol levels, increased withdrawal latency, increased release of vagally controlled gastrointestinal hormones, and increased weight gain. Together, these effects form an antistress pattern. Nonnoxious sensory stimuli release oxytocin and induce an effect spectrum similar to the one caused by oxytocin injections.
Organizational Principles of Cerebellar Neuronal Circuitry
Authors: Garwicz Martin , Ekerot Carl-Fredrik , Jörntell Henrik
Published: December 2017

We review our recent studies of cerebellar neuronal organization, emphasizing that consideration of organizational features of cerebellar circuitry represents a necessary step toward the understanding of how the cerebellum does what it does, in terms of both its internal information processing and its interaction with other motor structures.
Understanding the Role of Paracellular Transport in the Proximal Tubule
Authors: García Néstor H. , Ramsey Carla R. , Knox Franklyn G.
Published: December 2017

Fluid and solute reabsorption by the proximal tubule is the result of both transcellular and paracellular flux. The role of transcellular transport has been extensively studied, but the importance of paracellular flux has not been as thoroughly investigated. The purpose of this review is to update concepts about the contribution of paracellular transport for reabsorption by the proximal tubule.
Renal Proximal Tubular Albumin Reabsorption: Daily Prevention of Albuminuria
Authors: Gekle Michael
Published: December 2017

Although the glomerular filtration coefficient of albumin is small, the daily filtered load can be as much as 8 g. To prevent such massive losses of albumin, quantitative reabsorption along the proximal tubules is accomplished by “receptor”-mediated endocytosis. Albumin reaches the lysosomes where it is degraded to amino acids.