bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement by lanthanide of general anesthetic-induced GABAA-receptor current in rat septal cholinergic neurons in culture
Authors: Kumamoto E. , Murata Y.
Published: December 2017

1. Actions of lanthanide ions were examined on general anesthetic-induced currents mediated by the activation of gamma-aminobutyric acid-A receptors (GABAARs) in rat septal cholinergic neurons in primary culture, by means of a whole cell voltage-clamp technique. 2. La3+ enhanced a pentobarbital sodium (500 microM)-induced GABAAR current in a reversible and dose-dependent manner (median effective concentration = 15.7 microM; Hill coefficient = 1.58; 89% increase by 100 microM La3+). This action was independent of holding potentials (-34-26 mV), and was due to an increase in the apparent affinity for pentobarbital (295% increase with 100 microM La3+). 3. The action of La3+ on pentobarbital current was mimicked particularly by other lanthanide ions (Ce3+, Nd3+, Gd3+, Tb3+, Er3+, and Yb3+) and by Y3+ among a number of multivalent cations. There was no correlation between the potentiated proportions by lanthanide ions and their crystal ionic radii. 4. La3+ (100 microM) also augmented a GABAAR response evoked by either alpha-chloralose (500 microM), 2,6-diisopropylphenol (50 microM), or 3-alpha-hydroxy-5-alpha-pregnane-11,20-dione (20 microM) (144, 80, and 153% increase, respectively). 5. We suggest that the GABAAR channels on septal neurons are endowed with a novel “lanthanide site” whose activation results in a positive allosteric interaction with a binding site of the general anesthetics that is involved in a direct activation of GABAAR channels without any added exogenous GABA.
Backward and forward walking use different patterns of phase-dependent modulation of cutaneous reflexes in humans
Authors: Duysens J. , Tax A. A. , Murrer L. , Dietz V.
Published: December 2017

1. The phase-dependent modulation of medium-latency (P2) (70-80 ms) responses in semitendinosus (ST), biceps femoris (BF), rectus femoris (RF), and tibialis anterior (TA) was studied with the use of low-intensity stimulation (2 times perception threshold) of the sural nerve. The shocks were given in a random order at 16 phases of the step cycle in 10 normal subjects during forward walking (FW) or backward walking (BW) on a treadmill. 2. All subjects exhibited P2 responses in all muscles studied both during BW and FW. The amplitude of the facilitatory P2 responses showed phase-dependent changes that could not have been predicted on the basis of the variations in background activity throughout the step cycle. 3. During FW, the P2 facilitatory responses in BF were large (with respect to the background activity) throughout the whole step cycle except for a short period near the end of the swing phase. In ST the responses were smaller and appeared primarily at the end of the stance phase and during the first part of the swing phase. During the second half of swing the P2 responses were basically suppressive. A modulation pattern similar to the one in ST was found in RF and TA, except that there was no reversal to suppressive responses in the swing phase in RF. Instead, a reduction in the amplitude of the facilitatory P2 responses occurred. 4. During BW, the modulation pattern recorded in the same subjects was different from the one seen during FW. Large facilitatory P2 responses were present in all muscles in middle and late swing. In the first half of stance the responses were most prominently seen in BF and RF. At the end of stance and/or at the onset of swing the facilitatory responses decreased in amplitude (BF and RF) or reversed to P2 suppressions (ST and TA). 5. We conclude that there are both facilitatory and suppressive pathways from the sural nerve to the leg muscles studied and that the balance of activity in these paths is phase dependent during both FW and BW. It is suggested that the phase-dependent modulation of P2 responses could largely rely on a central motor program. During BW the same motor program is used as during FW, but possibly running in reverse, thereby causing a shift both in the timing of the reflex reversal and in the periods of reflex suppression.
A comparison of treadmill locomotion in adult cats before and after spinal transection
Authors: Belanger M. , Drew T. , Provencher J. , Rossignol S.
Published: December 2017

1. The aim of this study was to document the kinematics and the electromyographic activity recorded from several muscles during treadmill locomotion in the same cat (N = 4), before and after spinalization by using a chronic implantation method. Because identical experimental and control conditions were used, it was possible to establish similarities and differences in the timing and amplitude of the muscular activity and kinematics under the intact and spinal conditions in the same animal. The data presented in this paper were collected when the cats had fully recuperated a stable locomotor pattern, walking at a constant speed of approximately 0.4 m/s. 2. The adult spinal cats retained many of the general locomotor features and electromyographic (EMG) characteristics seen before transection. However, there were also important differences. 3. There was a reduction in the step length that was principally due to the forward placement of the paw at the onset of the stance. Similarly, there was a decrease in the step cycle duration which was attributed to a reduction of both the stance and swing phases. 4. The overall angular excursions of the hip, knee, and ankle were generally similar, although joints were sometimes more flexed at all phases of the step cycle. In contrast, the overall excursions of the metatarsophalangeal joints was much greater in all four cats after spinalization due to a paw drag during the initial portion of the swing phase that exaggerated the plantarflexion. 5. There was an increase in the EMG amplitude of the flexor muscles at two of three joints (i.e., hip, knee, and ankle) in each cat after spinalization. The change in the EMG amplitude of the extensors did not appear to be as consistent as that observed in the flexor muscles. When looking at each cat individually, the postspinalization extensor activity decreased at two of three joints in two cats, whereas the opposite was true for the other two cats. 6. There was a delay in the onset of the knee flexor (semitendinosus) activity while the ankle dorsiflexor (tibialis anterior) activity started earlier with respect to the beginning of the swing phase. The onset of hip flexors was somewhat more variable. This change in the timing of flexor activity was most probably responsible for the paw drag at the onset of the swing phase. 7. The present results reveal that despite the few differences, the spinal cord and the hindlimbs afferents are capable of generating very good locomotor patterns with almost normal kinematics and EMG characteristics.
Glutamate modulates intracellular Ca2+ stores in brain stem auditory neurons
Authors: Kato B. M. , Lachica E. A. , Rubel E. W.
Published: December 2017

1. Fura-2 imaging was used to measure the effects of glutamate on caffeine-sensitive Ca2+ stores in neurons of the avian cochlear nucleus, n. magnocellularis (NM). 2. On average, 100-mM caffeine stimulated a 250-nM increase in intracellular calcium ion concentration inverted question mark[Ca2+]i inverted question mark in Ca(2+)-free media; 1-mM glutamate significantly attenuated caffeine-stimulated Ca2+ responses. 3. The metabotropic glutamate receptor agonist, ACPD, also inhibited the caffeine-stimulated rise in [Ca2+]i. 4. Glutamate has an important role in regulating Ca2+ stores in NM neurons. Glutamate-deprivation (viz. cochlear removal) results in a rise in [Ca2+]i that may, in part, be the result of release from Ca2+ stores. We hypothesize that Ca(2+)-induced Ca2+ release stores (CICRs) may be involved in deprivation-induced cell death.
Permeation and block of dopamine-modulated potassium channels on rat striatal neurons by cesium and barium ions
Authors: Lin Y. J. , Greif G. J. , Freedman J. E.
Published: December 2017

1. In cell-attached patch-clamp recordings from freshly dissociated rat caudate-putamen neurons, an 85-pS inwardly rectifying K+ channel, which was previously found to be modulated by D2-like dopamine receptors, was blocked by externally applied BaCl2 or CsCl. 2. At concentrations between 100 and 500 microM, Ba2+ blockade was voltage dependent, with a greater block at hyperpolarized voltages, in a manner consistent with blockade of the channel pore. Single-channel currents were flickery, with intervening periods of more complete blockade, and block appeared to be time dependent, with an estimated electrical distance of 0.24 and an apparent dissociation constant of 205 microM at 0 mV. 3. At concentrations between 1 and 3 mM, Cs+ blockade was similarly voltage dependent, but without periods of longer blockade, with an electrical distance of 0.81 and an apparent dissociation constant of 625 microM at 0 mV. Cs+ could also permeate this channel at voltages near the K+ reversal potential. The current-voltage relationship displayed an anomalous negative slope conductance, in a manner inconsistent with a single-ion pore. 4. Smaller-conductance, dopamine-insensitive channels were blocked more potently by both Ba2+ and Cs+ than was the 85-pS channel, reflecting differences between inwardly rectifying K+ channels mediating resting conductance and those mediating dopamine receptor responses in striatal neurons.
Suppression of K+ conductance by metabotropic glutamate receptor in acutely dissociated large cholinergic neurons of rat caudate putamen
Authors: Takeshita Y. , Harata N. , Akaike N.
Published: December 2017

1. Responses to metabotropic glutamate receptor (mGluR) activation were investigated in acutely dissociated rat neostriatal (caudate putamen, CP) large cholinergic neurons, with the use of a nystatin-perforated patch-clamp technique. 2. Application of L-glutamate (Glu) in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) induced a slow inward current accompanied by a decrease in membrane conductance at a holding potential (VH) of -44 mV. 3. The ratio of the maximal amplitude of the slow inward metabotropic glutamate (mGlu) response to that of the ionotropic glutamate response for large cholinergic CP neurons was larger than that for the hoppocampal CA1, CA3, and dentate gyrus neurons the nucleus tractus solitarii neuron, cerebellar Purkinje neuron, and granule cell of the main olfactory bulb. The threshold and half-maximal effective concentration values of these mGlu responses were 10- to 30-fold lower than those of the respective ionotropic responses. 4. Specific agonists of the mGluR, quisqualate (QA), (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (tACPD), (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD], and (2S,3S,4S)-alpha-carboxycyclopropyl-glycine [L-CCG-1), similarly induced slow inward currents at the same VH. The relative affinities of the mGlu agonists were QA > Glu > L-CCG-1 > (1S,3R)-ACPD. L-CCG-1 did not induce any current at concentrations < 10(-6) M. 5. DL-2-amino-3-phosphonopropionic acid or DL-2-amino-4-phosphonobutyric acid did not block the mGlu response, whereas (RS)-alpha-methyl-4-carboxyphenyl-glycine, a selective mGluR antagonist, partially reduced the mGlu response. 6. The reversal potential of the mGlu response was close to the K+ equilibrium potential, and it shifted by 56.4 mV for a 10-fold change in extracellular K+ concentration. In 90.6% of the neurons tested, the instantaneous current induced by hyperpolarizing voltage steps was markedly suppressed during the mGlu response. In 9.4% of the neurons, the currents elicited by step pulses showed a voltage-dependent slow relaxation that was not affected by mGluR activation. 7. Under the current-clamp mode, the slow afterhyperpolarization (AHP) following a spontaneous discharge was not affected by tACPD. The AHP current was not blocked under the voltage-clamp mode, either. 8. (1S,3R)-ACPD or Glu in the presence of CNQX elicited membrane depolarization accompanied by increased rate of action potentials under the current-clamp mode. Tetrodotoxin had no effect on the membrane depolarization. 9. These results indicate that the mGluR on large cholinergic CP neurons is mainly of the mGluR1 and/or mGluR5 type, and it plays a significant role in controlling the membrane potential by way of suppressing the leak K+ conductance.
Forskolin enhancement of opioid currents in rat locus coeruleus neurons
Authors: Osborne P. B. , Williams J. T.
Published: December 2017

1. Opioids are known to hyperpolarize all neurons in the nucleus locus coeruleus (LC) and to inhibit adenylyl cyclase. Recent work has shown that activation of adenylyl cyclase with forskolin increased the amplitude of the opioid hyperpolarization in LC cells. The aim of the present study was to determine the mechanism of this augmented hyperpolarization. 2. Agonist-induced currents were studied in LC cells in brain slices using both intracellular and whole cell recordings. Forskolin increased the amplitude of mu-opioid- and alpha 2-adrenoceptor-mediated currents by approximately 30% of control measured at -60 mV. This effect of forskolin was dependent on the concentration having a threshold of approximately 1 microM and a peak effect at approximately 30 microM. Dideoxyforskolin (30 microM) caused a small reduction (-52 +/- 28 pA, mean +/- SE) in the amplitude of the opioid current. 3. Forskolin increased the agonist current in the outward direction over the entire potential range between -140 and -50 mV when recordings were made from neurons in cells recorded from slices cut in the horizontal plane. This augmented current produced a shift of the apparent reversal potential to more negative values. 4. Both the forskolin augmentation of the opioid current and the opoid current itself were reduced when the space clamp was improved by cutting the slice in the coronal plane, increasing the extracellular potassium concentration, and treating the slice with carbenoxolone. In addition, forskolin did not change the reversal potential of the opoid current. When expressed as a percentage change from control, forskolin had no significant effect on the opioid current in carbenoxolone (-13 +/- 13%) but produced a small augmentation in high extracellular potassium (15 +/- 4%) and coronoal slices (31 +/- 12%). 5. Two models were tested to explain the action of forskolin, one where cells are coupled electronically by a forskolin-sensitive conductance (coupled-cell model) and a second where opioids mediate an inhibition of a forskolin-induced cation conductance (2-conductance model). The experimental results were fit well only by the coupled-cell model, which predicted that the opioid/forskolin interaction is indirect and occurs primarily in response to forskolin increasing the degree of electrotonic coupling between LC neurons. The consequence of increased coupling would be to augment synchronous activity within the nucleus.
Of known neurotransmitters, glutamate is the most likely to be released from chick cochlear hair cells
Authors: Kataoka Y. , Ohmori H.
Published: December 2017

1. Experiments were performed to identify the excitatory amino acid (EAA) released from cochlear hair cells isolated from chick. An isolated hair cell was transported and closely apposed to a cultured granule cell or a Purkinje cell, and current responses were studied in these cell pairs when the apposed hair cell was depolarized. 2. The apposed hair cell was voltage clamped at -65 mV by a nystatin perforated-patch recording technique and the membrane potential was step changed to -10 or 0 mV to induce a release of neurotransmitter. In the granule cell voltage clamped at +55 mV, the hair cell membrane depolarization induced outward currents through the activation of the N-methyl-D-aspartate subtype of glutamate receptors. In the Purkinje cell voltage clamped at -60 mV, however, the hair cell depolarization could not induce any current responses. 3. Concentration-response relations for three endogenous EAAs (L-glutamate, L-aspartate, and L-homocysteate) were studied in the granule cell and in the Purkinje cell. The granule cell was most sensitive to glutamate, whereas these three EAAs did not show great sensitivity differences in the Purkinje cell and the half-maximum current was obtained at EAA concentrations of 17-60 microM. Concentrations of glutamate, aspartate, and homocysteate inducing the half-maximum current in the granule cell were 1.1, 11, and 10 microM, respectively. 4. The depolarization of the hair cell induced outward current (70 +/- 33 pA, mean +/- SD, n = 8) in the apposed granule cell voltage clamped at +55 mV. This current was equivalent to the current size induced by 0.33 microM glutamate, 5 microM aspartate, or 2 microM homocysteate. However, the critical concentration (0.33 microM) of glutamate failed to induce any current in the Purkinje cell voltage clamped at -60 mV. But the critical concentrations of the other two amino acids did evoke inward currents in the Purkinje cell. 5. These observations suggest that, of known neurotransmitter candidates, glutamate is the most likely to be released by cochlear hair cells in the chick. 6. Purkinje cells had an EAA-induced current that was not suppressed by 2-amino-5-phosphonovalerate (200 microM) or by 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM). The current was dominant at low concentrations of EAAs (approximately 1.0 microM). This EAA-induced current was Na+ dependent and was likely carried through the high-affinity EAA transporter.
Motor unit activity during human single joint movements
Authors: Garland S. J. , Cooke J. D. , Miller K. J. , Ohtsuki T. , Ivanova T.
Published: December 2017

1. To explore the neural control of single joint movements in humans, the activity of 47 motor units in triceps brachii muscle was recorded during elbow flexion and extension movements. Movements were performed with different but changing deceleration magnitudes, while the acceleration magnitude was kept constant, to determine the relationship between motor unit activity and the acceleration and deceleration characteristics of single joint movements. 2. The number of motor unit action potentials was found to vary with the magnitude of the movement deceleration. In addition the duration of the discharge of a motor unit was found to parallel the duration of the acceleration phase of the movement, when the acceleration duration was varied while acceleration magnitude was kept constant. 3. Approximately half of the recorded motor units in triceps brachii were active both in the initiation and in the termination of the extension movements. However, motor units were identified that participated in specific phases of the movement (i.e., either during the 1st agonist or 2nd agonist burst of muscle activity) depending on the magnitude of the acceleration or deceleration. 4. During flexion movements, when the triceps muscle served as an antagonist, approximately half of the motor units were recruited only when the magnitude of the flexion deceleration was large. Further, this deceleration magnitude was larger than that evident during the extension movements in which the motor unit discharged. 5. The findings of this study demonstrate that the nervous system activates the same motor units whether the muscle is functioning as an agonist or antagonist so as to control the characteristics of acceleration and deceleration of single joint movements.
Glutamate and N-acetylaspartylglutamate block HVA calcium currents in frog olfactory bulb interneurons via an mGluR2/3-like receptor
Authors: Bischofberger J. , Schild D.
Published: December 2017

1. We investigated the glutamate-mediated modulation of voltage-activated calcium currents in cultured interneurons of the olfactory bulb of Xenopus laevis, with the use of standard patch-clamp whole-cell recordings. 2. Glutamate and N-acetylaspartylglutamate (NAAG) activated (2S,1'R,2'R,3'R)-2-(2,3-dicarboxy-cyclopropyl)glycin-sens iti ve metabotropic glutamate receptors at olfactory bulb interneurons and thereby inhibited calcium influx through presynaptic voltage-gated calcium channels. 3. The glutamate- or NAAG-mediated blockage of calcium channels showed indistinguishable dose-response curves, with K1/2 = 388 and 350 nM for glutamate and NAAG, respectively. At saturating concentrations of glutamate or NAAG, approximately 40% of the maximum calcium currents were blocked. 4. It is concluded that glutamate, which excites interneurons at olfactory bulb reciprocal synapses, also causes a reduction of gamma-aminobutyric acid-mediated feedback inhibition at these synapses by activating a metabotropic-glutamate-receptor-2/3-like receptor.
Calcium dependence of LTP induced by 2-deoxyglucose in CA1 neurons
Authors: Tekkok S. , Krnjevic K.
Published: December 2017

1. As previously reported, in hippocampal slices from Sprague-Dawley rats, 13-min applications of 2-deoxy-D-glucose (2-DG) (substituting 10 mM 2-DG for glucose)-which sharply depress field excitatory postsynaptic potentials (EPSPs)-are followed by a sustained potentiation of the initial slopes of EPSPs (2-DG-LTP). 2. Such 2-DG-LTP is not prevented by exposing slices to Ca(2+)-free medium for 25 min before the 13-min 2-DG applications (in Ca(2+)-free medium). Therefore 2-DG-LTP is not dependent on influx of external Ca2+ during the 2-DG applications. 3. When the Ca(2+)-free conditions begin 15 min before, and are maintained for 10 min after, the 13-min 2-DG applications (in Ca(2+)-free medium), 2-DG-LTP is either totally suppressed or much reduced. A delayed Ca2+ influx thus plays a crucial role in the induction of 2-DG-LTP. 4. Much longer Ca(2+)-free pretreatment (for 77 min) largely abolishes 2-DG-LTP. Therefore Ca2+ release from a compartment (presumably intracellular) that is not readily depleted is also important for the induction of 2-DG-LTP. 5. This intracellular Ca2+ store is sensitive to dantrolene sodium (10 microM)-which prevents 2-DG-LTP-but not 10 microM thapsigargin. 2-DG-LTP of isolated N-methyl-D-aspartate-receptor-mediated EPSPs is only partly reduced by dantrolene. 6. Dantrolene (10 microM) also reduces or abolishes posttetanic potentiation, but not paired-pulse facilitation. 7. Depotentiation by 1-Hz stimulation is abolished by 20 microM dantrolene. 8. In contrast to the above, long-term potentiation (LTP) elicited by tetanic stimulation is prevented by 10 microM thapsigargin but not by dantrolene (< or = 50 microM). 9. In conclusion, two mechanisms of intracellular Ca2+ concentration increase appear to be essential for LTP induction by 2-DG. One is Ca2+ influx after the 2-DG application; the other is Ca2+ release from a dantrolene-sensitive internal store. The opposite effects of thapsigargin and dantrolene on 2-DG-LTP and tetanic LTP suggest that distinct internal sources of Ca2+ may be needed for the induction of these two forms of LTP.
Transmitter packaging at frog neuromuscular junctions exposed to anticholinesterases; the role of second-stage acetylcholine loading
Authors: Naves L. A. , Van der Kloot W.
Published: December 2017

1. This investigation was undertaken to explore an unexpected effect of vesamicol, an agent that inhibits active acetylcholine (ACh) uptake into isolated synaptic vesicles. Previous studies at the neuromuscular junction showed that vesamicol makes miniature end-plate currents (MEPCs) smaller only after tens of thousands of quanta have been released. Inhibiting acetylcholinesterase (AChE) makes the MEPCs larger than normal. Our unexpected finding was that with the AChE inhibitor present, adding 2 microM (-)-vesamicol decreases the size of the MEPCs by approximately 30%. The decrease was apparent within 15-30 min, during which only a few thousand quanta had been released. 2. Experimental tests showed that the (-)-vesamicol treatment is unlikely to be acting postsynaptically. For example, it did not slow the rise of MEPCs, which would occur if the endplate receptors were blocked. 3. When AChE was inhibited, three treatments expected to block active choline (Ch) uptake into the presynaptic terminals decreased MEPC size: 1) elevating extracellular K+ to diminish the Na+ electrochemical gradient required for Ch uptake; 2) replacing extracellular Na+ with methylamine+; and 3) adding hemicholinium-3 (HC-3), an inhibitor of the Ch transporter. These treatments did not act by reactivating AChE, blocking the endplate ACh receptor, or by enhancing the desensitization of the ACh receptor. 4. Previous evidence suggests that synaptic vesicles are formed and partially filled with ACh in the cytoplasm and then receive additional ACh when they attach to the active zones, a process that is called second-stage loading. We conclude that the MEPCs are becoming smaller when second-stage loading is blocked by (-)-vesamicol or when the supply of ACh in the cytoplasm of the motor nerve terminal is depleted. 5. To follow the time course of second-stage loading, we used the false transmitter precursor monoethylcholine (MECh). It enters the terminal and is transformed into acetylmonoethylcholine (AMECh). When 200 microM MECh was placed in the extracellular solution and the AChE was inhibited, MEPC size was significantly smaller after 10 min. MEPC size increased once again over a period of time when MECh was removed from the extracellular solution and replaced with Ch. 6. We conclude that at the neuromuscular junction second-stage loading is responsible for loading a significant fraction of the ACh into the quanta.
Medial Superior Olive in the Free-Tailed Bat: Response to Pure Tones and Amplitude-Modulated Tones
Authors: Grothe Benedikt , Park Thomas J. , Schuller Gerd
Published: December 2017

Grothe, Benedikt, Thomas J. Park, and Gerd Schuller. Medial superior olive in the free-tailed bat: response to pure tones and amplitude-modulated tones. J. Neurophysiol. 77: 1553–1565, 1997. In mammals with good low-frequency hearing and a moderate to large interear distance, neurons in the medial superior olive (MSO) are sensitive to interaural time differences (ITDs). Most small mammals, however, do not hear low frequencies and do not experience significant ITDs, suggesting that their MSOs participate in functions other than ITD coding. In one bat species, the mustached bat, the MSO is a functionally monaural nucleus, acting as a low-pass filter for the rate of sinusoidally amplitude-modulated (SAM) stimuli. We investigated whether the more typical binaural MSO of the Mexican free-tailed bat also acts as an SAM filter. We recorded from 60 MSO neurons with their best frequencies covering the entire audiogram of this bat. The majority revealed bilateral excitation and indirect evidence for inhibition (EI/EI; 55%). The remaining neurons exhibited reduced inputs, mostly lacking ipsilateral inputs (28% I/EI; 12% O/EI; 5% EI/O). Most neurons (64%) responded with a phasic discharge to pure tones; the remaining neurons exhibited an additional sustained component. For stimulation with pure tones, two thirds of the cells exhibited monotonic rate-level functions for ipsilateral, contralateral, or binaural stimulation. In contrast, nearly all neurons exhibited nonmonotonic rate-level functions when tested with SAM stimuli. Eighty-eight percent of the neurons responded with a phase-locked discharge to SAM stimuli at low modulation rates and exhibited low-pass filter characteristics in the modulation transfer function (MTF) for ipsilateral, contralateral, and binaural stimulation. The MTF for ipsilateral stimulation usually did not match that for contralateral stimulation. Introducing interaural intensity differences (IIDs) changed the MTF in unpredictable ways. We also found that responses to SAMs depended on the carrier frequency. In some neurons we measured the time course of the ipsilaterally and contralaterally evoked inhibition by presenting brief frequency-modulated sweeps at different ITDs. The duration and timing of inhibition could be related to the SAM cutoff for binaural stimulation. We conclude that the response of the MSO in the free-tailed bat is created by a complex interaction of inhibition and excitation. The different time constants of inputs create a low-pass filter for SAM stimuli. However, the MSO output is an integrated response to the temporal structure of a stimulus as well as its azimuthal position, i.e., IIDs. There are no in vivo results concerning filter characteristics in a “classical” MSO, but our data confirm an earlier speculation about this interdependence based on data accessed from a gerbil brain slice preparation.
Visualization of the Information Flow Through Human Oculomotor Cortical Regions by Transcranial Magnetic Stimulation
Authors: Terao Yasuo , Fukuda Hideki , Ugawa Yoshikazu , Hikosaka Okihide , Hanajima Ritsuko , Furubayashi Toshiaki , Sakai Katsuyuki , Miyauchi Satoru , Sasaki Yuka , Kanazawa Ichiro
Published: December 2017

Terao, Yasuo, Hideki Fukuda, Yoshikazu Ugawa, Okihide Hikosaka, Ritsuko Hanajima, Toshiaki Furubayashi, Katsuyuki Sakai, Satoru Miyauchi, Yuka Sasaki, and Ichiro Kanazawa. Visualization of the information flow through human oculomotor cortical regions by transcranial magnetic stimulation. J. Neurophysiol. 80: 936–946, 1998. We investigated the topography of human cortical activation during an antisaccade task by focal transcranial magnetic stimulation (TMS). We used a figure-eight shaped coil, with the stimulus intensity set just above the threshold for activation of the hand motor areas but weak enough not to elicit blinks. TMS was delivered at various time intervals (80, 100, and 120 ms) after target presentation over various sites on the scalp while the subjects performed the antisaccade task. It was possible to elicit a mild but significant delay in saccade onset over 1) the frontal regions (a region 2–4 cm anterior and 2–4 cm lateral to hand motor area) and 2) posterior parietal regions (6–8 cm posterior and 0–4 cm lateral to hand motor area) regardless of which hemisphere was stimulated. The frontal regions were assumed to correspond to a cortical region including the frontal eye fields (FEFs), whereas the parietal regions were assumed to represent a wide region that includes the posterior parietal cortices (PPCs). The regions inducing the delay shifted from the posterior parietal regions at an earlier interval (80 ms) to the frontal regions at a later interval (100 ms), which suggested an information flow from posterior to anterior cortical regions during the presaccadic period. At 120 ms, the effect of TMS over the frontal regions still persisted but was greatly diminished. Erroneous prosaccades to the presented target were elicited over a wide cortical region including the frontal and posterior parietal regions, which again showed a forward shift with time. However, the distribution of effective regions exhibited a clear contralateral predominance in terms of saccade direction. Our technique provides a useful method not only for detecting the topography of cortical regions active during saccadic eye movement, but also for constructing a physiological map to visualize the temporal evolution of functional activities in the relevant cortical regions.
Injection of MK-801 Affects Ocular Dominance Shifts More Than Visual Activity
Authors: Daw N. W. , Gordon B. , Fox K. D. , Flavin H. J. , Kirsch J. D. , Beaver C. J. , Ji Q.-H. , Reid S.N.M. , Czepita D.
Published: December 2017

Daw, N. W., B. Gordon, K. D. Fox, H. J. Flavin, J. D. Kirsch, C. J. Beaver, Q.-H. Ji, S.N.M. Reid, and D. Czepita. Injection of MK-801 affects ocular dominance shifts more than visual activity. J. Neurophysiol. 81: 204–215, 1999. Kittens were given intramuscular injections of the N-methyl-d-aspartate (NMDA) antagonist MK-801 twice daily (morning and midday) during the peak of the period of susceptibility for ocular dominance changes. They were then exposed to light with one eye closed for 4 h after each injection. The ocular dominance of these kittens was shifted significantly less than that of kittens injected with saline and exposed to light over the same period at the same age. After recording a sample of cells for an ocular dominance histogram, the kittens were injected with the same dose of MK-801 that was used during rearing to observe its effect on the activity of single cells in the visual cortex. In the majority of cells (7/13) there was no significant change in activity. Positive evidence for a reduction in activity was seen in only a minority (3/13) of cells. In a separate series of experiments, dose-response curves were measured for cells in the visual cortex in response to iontophoresis of NMDA or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and the effect of an injection of MK-801 on these curves was measured. MK-801, at doses similar to those used in the ocular dominance experiments, had a significant effect on the dose-response curves for NMDA, but little effect on the dose-response curves for AMPA, or the visual responses of the cells. We conclude that ocular dominance shifts can be reduced significantly by a treatment that has little effect on the level of activity of cells in the visual cortex but does specifically affect the responses of the cells to NMDA as opposed to the responses to AMPA.
Desynchronizing Responses to Correlated Noise: A Mechanism for Binaural Masking Level Differences at the Inferior Colliculus
Authors: Palmer Alan R. , Jiang Dan , McAlpine David
Published: December 2017

Desynchronizing responses to correlated noise: a mechanism for binaural masking level differences at the inferior colliculus. We examined the adequacy of decorrelation of the responses to dichotic noise as an explanation for the binaural masking level difference (BMLD). The responses of 48 low-frequency neurons in the inferior colliculus of anesthetized guinea pigs were recorded to binaurally presented noise with various degrees of interaural correlation and to interaurally correlated noise in the presence of 500-Hz tones in either zero or π interaural phase. In response to fully correlated noise, neurons’ responses were modulated with interaural delay, showing quasiperiodic noise delay functions (NDFs) with a central peak and side peaks, separated by intervals roughly equivalent to the period of the neuron’s best frequency. For noise with zero interaural correlation (independent noises presented to each ear), neurons were insensitive to the interaural delay. Their NDFs were unmodulated, with the majority showing a level of activity approximately equal to the mean of the peaks and troughs of the NDF obtained with fully correlated noise. Partial decorrelation of the noise resulted in NDFs that were, in general, intermediate between the fully correlated and fully decorrelated noise. Presenting 500-Hz tones simultaneously with fully correlated noise also had the effect of demodulating the NDFs. In the case of tones with zero interaural phase, this demodulation appeared to be a saturation process, raising the discharge at all noise delays to that at the largest peak in the NDF. In the majority of neurons, presenting the tones in π phase had a similar effect on the NDFs to decorrelating the noise; the response was demodulated toward the mean of the peaks and troughs of the NDF. Thus the effect of added tones on the responses of delay-sensitive inferior colliculus neurons to noise could be accounted for by a desynchronizing effect. This result is entirely consistent with cross-correlation models of the BMLD. However, in some neurons, the effects of an added tone on the NDF appeared more extreme than the effect of decorrelating the noise, suggesting the possibility of additional inhibitory influences.
Localization of a blood pressure QTL on rat chromosome 1 using Dahl rat congenic strains
Authors: SAAD YASSER , GARRETT MICHAEL R. , LEE SOON JIN , DENE HOWARD , RAPP JOHN P.
Published: December 2017

Saad, Yasser, Michael R. Garrett, Soon Jin Lee, Howard Dene, and John P. Rapp. Localization of a blood pressure QTL on rat chromosome 1 using Dahl rat congenic strains. Physiol. Genomics 1: 119–125, 1999.—We previously reported that markers on rat chromosome 1 are genetically linked to blood pressure in an F2 population derived from Dahl salt hypertension-sensitive (S) and Lewis (LEW) rats. Because there was evidence for more than one blood pressure quantitative trait locus (QTL) on chromosome 1, an initial congenic strain introgressing a large 118-centimorgan (cM) segment of LEW chromosome 1 into the S background had been constructed. This initial congenic strain had a reduced blood pressure compared with S rats, proving the existence of a blood pressure QTL, but not giving a good localization of the QTL. In the present work a series of five overlapping congenic substrains were produced from the original congenic strain in order to localize a blood pressure QTL to a 25-cM region near the center of chromosome 1. The congenic substrains also ruled out the Sa locus as a blood pressure QTL in the S vs. LEW comparison because the Sa locus was contained in a congenic substrain that did not alter blood pressure.
Keeping a Cool Head
Authors: Cabanac M
Published: December 2017

The mammalian brain has poor tolerance to increased temperature. However, when body core temperature rises during exercise or heat stress, the temperature of the brain can remain at a lower level, somewhat independent of the rest of the body. In several mammals the cooling of the brain is related to anatomically well-defined countercurrent heat exchangers. Humans lack these distinct anatomic structures, but significant cooling of the brain can nevertheless occur. Such selective cooling of the brain may have important medical implicantions.
Glucocorticoid Hormones in Stress: Physiological and Pharmacological Actions
Authors: Munck A , Guyre PM
Published: December 2017

What are the normal functions of the adrenal glucocorticoid hormones? This seemingly simple question has not yet any simple agreed-on answer. In the half-century since the glucocorticoids were distinguished from other cortical steroids, the question of their physiological functions has generated much inconclusive debate. Likewise, questions of their role in disease and therapy lack definitive answers. The authors propose that there is no fundamental distinction between the physiological and pharmacological effects of glucocorticoids and that their inhibitory actions on inflammatory and immune responses are concerned with modulating the body's defense mechanisms.
How Is the Respiratory Rhythm Generated? A Model
Authors: Richter DW , Ballantyne D , Remmers JE
Published: December 2017

This article presents a model of the neuronal network that generates the rhythm for respiratory movements. It incorporates new data on the synaptic activity and discharge properties of respiratory neurons in the brain stem and on the modulation of their excitability by nonsynaptic intrinsic membrane properties. The model allows a description of the control sequence that generates the rhythm.
Mechanical Transduction: Unification?
Authors: Sachs F
Published: December 2017

The transduction of mechanical stimuli into electrical responses is essential for audition, kinesthesis, proprioception, and autonomic sensation of pressure and volume. The primary event in transduction is the opening of an ion channel whose linkage to the cytoskeleton provides high sensitivity. When linked to adapting mechanical structures, this scheme can account for the presently known properties of various mechanical transducers.
Tubular Reabsorption of Amino Acids in the Kidney
Authors: Silbernagl S
Published: December 2017

Any news about renal reabsorption of amino acids? Today we understand tubular amino acid reabsorption much better than we did 10 years ago. The news about amino acids reported here includes the reabsorption of dipeptides and also the digestion of oligopeptides within the tubular lumen and subsequent absorption of the free constituent amino acids.
The Crystalline Lens of the Eye: An Organismal Microcosm
Authors: Bentley PJ
Published: December 2017

The lens of the eye is transparent due to several special characteristics, including the lack of a blood supply, a tight geometric arrangement of its cells, and high concentrations of special proteins called crystallins, which in solution provide a transparent medium. Opacities of the lens (cataracts), which are especially prevalent in old age, appear to result from damage to lens proteins and cell membranes. Causes of such damage include radiation, sunlight toxic chemicals and drugs, and, of special current interest, naturally occurring oxidants.
Control of Sodium Excretion: The Kidney Produces Under Pressure
Authors: Knox FG , Granger JP
Published: December 2017

Sodium excretion is controlled by an integration of physical, neural, and hormonal regulatory systems. The major systems involved in retention of sodium include the renin-angiotensin-aldosterone system and the sympathetic nervous system. In response to increased sodium intake, the sodium-retaining systems are inhibited and natriuretic hormones are activated. Pressures and flows within the microcirculation of the kidney, in concert with neural and hormonal systems, are important effector mechanisms that work to regulate sodium excretion.
Symbiotic Exploitation of Hydrogen Sulfide
Authors: Somero GN
Published: December 2017

It has long been axiomatic knowledge that all organic life on earth, animal as well as plant, is ultimately based on energy from the sun. Not so any more. Recent discoveries at the bottom of the ocean have revealed rich communities of animals that use entirely novel physiological mechanisms to obtain energy. These communities surround hot springs where emerging water contains high concentrations of hydrogen sulfide. This highly toxic compound provides the energy that makes the animals largely if not completely independent of the photosynthetic food chain.
On the Concept of Resting Muscle
Authors: Mommaerts Wilfried F. H. M.
Published: December 2017

It may appear a simple matter to define what a resting muscle is, but it is not as simple as it may initially appear. Professor Mommaerts in this essay discusses the complications of defining and achieving a truly resting state, perhaps an unreachable goal
The Remarkable Vestibuloocular Reflex
Authors: Jones GM
Published: December 2017

The amazing ability of the eye to remain fixed on a target during rapid movements of the head depends on the familiar automatic control mechanism known as the vestibuloocular reflex. This article presents new information about this reflex in the control of eye movement and the stabilization of eye position. The reflex is found to be highly adaptive, including the curious recent finding that imaginary visual information can initiate plastic changes.
How Plasma Macromolecules Cross the Endothelium
Authors: Simionescu M , Ghitescu L , Fixman A , Simionescu N
Published: December 2017

Plasma macromolecules can, in some tissues, cross the capillary wall and enter the interstitial space by a specific mechanism of transcytosis in which a macromolecule is first recognized by its receptor on the luminal surface of endothelial cells. A cluster of receptors bearing their cargo is confined to a vesicle that crosses the cells and discharges the macromolecules on the abluminal surface. The process may be especially important for transport of large molecules, such as albumin, transferrin, insulin, and low-density-lipoprotein, to the cells where they are needed.
Glucose Sensors in Viscera and Control of Blood Glucose Level
Authors: Niijima A , Mei N
Published: December 2017

In addition to the well-known glucose-responsive neurons in the hypothalamus, recent studies of sensory signals from the visceral area have brought us a new understanding of the mechanisms that control the blood glucose level. The activity of efferent fibres to the pancreas and the liver is precisely modulated, not only by central hypothalamic glucoreceptors but also by peripheral (hepatic and intestinal) glucoreceptors.
Membrane Transport and Hydrolytic Enzymes Under Physiological Vs. Acute Experimental Conditions
Authors: Ugolev AM
Published: December 2017

When examined in chronic preparations of healthy animals that have fully recovered from experimental surgery, the integrated functions of intestinal hydrolytic enzymes coupled to transport systems for the uptake of nutrients have very different properties from those observed in acute experiments or in isolated preparations.
Billfish Brain and Eye Heater: A New Look at Nonshivering Heat Production
Authors: Block BA
Published: December 2017

Several large oceanic fish have a heat-producing tissue that warms their brain and eyes. This tissue is derived from an eye muscle and consists of cells that are specialized for heat production and not for contraction. Heat production in this unusual muscle tissue may be associated with the ATP-dependent cycling of Ca2+ at the sarcoplasmic reticulum. This type of heat production is probably prevalent in many animals and is associated with malignant hyperthermia in humans.
Is the Epididymis a Kidney Analogue?
Authors: Hinton BT , Turner TT
Published: December 2017

The epithelia of the epididymis and kidney have physiological and structural similarities that may relate to their similar embryological origin. Both epithelia control their intraluminal microenvironment via secretory and absorptive processes. Considering the epididymis in the light of what is known about renal physiology may help us grain fresh insight into its functions.
The Nonpregnant Uterus as an Endocrine Organ
Authors: Freeman ME
Published: December 2017

The mammalian uterus is well known as an endocrine organ whose secretions are responsible for the maintenance of pregnancy and the preparation of the mammary gland for lactation. There is now evidence that the nonpregnant uterus secretes a hormone that regulates pituitary function in the nonpregnant mammal. It secretes a protein that enters the bloodstream and is transported to the pituitary gland where it acts to inhibit prolactin secretion.
Immobilized Antibodies - A Newer Approach to Measurement of Released Neuropeptides
Authors: Duggan AW , Hendry I
Published: December 2017

Measurement of transmitter release the central nervous system has been difficult because the collection device often is many times larger than the releasing neurones and hence produces considerable trauma. By immobilizing binding proteins for released compounds to the outer surface of glass microelectrodes, we can now measure release of neuropeptides in the absence of significant trauma.
How Muscle Spindels Signal Changes of Muscle Length
Authors: Emonet-Denand F , Hunt CC , Laporte Y
Published: December 2017

Information on muscle length is essential for the regulation of posture and movements. This informationis provided to the central nervous system by the sensory endings of the muscle spindles. The primary endings possess a dynamic sensitivity that is much greater jkfor small than for large amplitude changes. This sensitivity is due to the properties of certain intrafusal muscles fibres, the nuclear bag fibres, and their sensory terminals.
Eggs, Sperm, and Sugar. A Recipe for Fertilization
Authors: Wassarman PM
Published: December 2017

The extracellular coat surrounding unfertilized mammalian eggs contains receptors that sperm recognize and bind in a species-specific manner during fertilization. These sperm receptors are glycoproteins that regulate interactions between eggs and sperm both before and after fertilization. Recent evidence suggests that it is certain of the sperm receptor's oligosaccharides that mediate gamete recognition and binding during mammalian fertilization.
Suckling-Induced Rise in Prolactin: Mediation by Prolactin-Releasing Factor From Posterior Pituitary
Authors: Ben-Jonathan N , Hyde JF , Murai I
Published: December 2017

The suckling-induced rise in prolactin, an anterior pituitary hormone that is essential for the maintenance of lactation, is mediated by the posterior pituitary. The posterior pituitary contains prolactin-releasing factor (PRF), a small peptide that is distinct from known prolactin secretagogues. The hypothalamus, the site of all known releasing hormones, has only little PRF activity. Pituitary stalk secretion abolishes the PRF activity in the posterior pituitary, indicating that it originates in the hypothalamus, perhaps as a biologically inactive precursor. The chemical identity of PRF is unknown but it appears to play an important role during lactation and might also be involved in the pathology of hyperprolactinea.