bluuebunny/crossref_metadata_2025 huggingface dataset:
Excitatory But Not Inhibitory Synaptic Transmission Is Reduced in Lethargic (Cacnb4lh) and Tottering (Cacna1atg) Mouse Thalami
Authors: Caddick Sarah J. , Wang Chunsheng , Fletcher Colin F. , Jenkins Nancy A. , Copeland Neal G. , Hosford David A.
Published: December 2017

Excitatory but not inhibitory synaptic transmission is reduced in lethargic ( Cacnb4lh) and tottering ( Cacna1atg) mouse thalami. Recent studies of the homozygous tottering ( Cacna1atg) and lethargic mouse ( Cacnb4lh) models of absence seizures have identified mutations in the genes encoding the α1A and β4 subunits, respectively, of voltage-gated Ca2+channels (VGCCs). β subunits normally regulate Ca2+currents via a direct interaction with α1 (pore-forming) subunits of VGCCs, and VGCCs are known to play a significant role in controlling the release of transmitter from presynaptic nerve terminals in the CNS. Because the gene mutation in Cacnb4lhhomozygotes results in loss of the β4 subunit’s binding site for α1 subunits, we hypothesized that synaptic transmission would be altered in the CNS of Cacnb4lhhomozygotes. We tested this hypothesis by using whole cell recordings of single cells in an in vitro slice preparation to investigate synaptic transmission in one of the critical neuronal populations that generate seizure activity in this strain, the somatosensory thalamus. The primary finding reported here is the observation of a significant decrease in glutamatergic synaptic transmission mediated by both N-methyl-d-aspartate (NMDA) and non-NMDA receptors in somatosensory thalamic neurons of Cacnb4lhhomozygotes compared with matched, nonepileptic mice. In contrast, there was no significant decrease in GABAergic transmission in Cacnb4lhhomozygotes nor was there any difference in effects mediated by presynaptic GABABreceptors. We found a similar decrease in glutamatergic but not GABAergic responses in Cacna1atghomozygotes, suggesting that the independent mutations in the two strains each affected P/Q channel function by causing defective neurotransmitter release specific to glutamatergic synapses in the somatosensory thalamus. This may be an important factor underlying the generation of seizures in these models.
Modulation of Inhibitory Synaptic Potentials in the Piriform Cortex
Authors: Patil Madhvi M. , Hasselmo Michael E.
Published: December 2017

Modulation of inhibitory synaptic potentials in the piriform cortex. Intracellular recordings from pyramidal neurons in brain slice preparations of the piriform cortex were used to test results from a computational model about the effects of cholinergic agonists on inhibitory synaptic potentials induced by stimulation of afferent fibers in layer Ia and association/intrinsic fibers in layer Ib. A simple model of piriform cortex as an associative memory was used to analyze how suppression of inhibitory synaptic transmission influenced performance of the network. Levels of suppression of excitatory synaptic transmission were set at levels determined in previous experimental work. Levels of suppression of inhibitory synaptic transmission were then systematically varied within the model. This modeling work demonstrated that suppression of inhibitory synaptic transmission in layer Ib should be stronger than suppression of inhibitory synaptic transmission in layer Ia to keep activity levels high enough for effective storage. Experimental data showed that perfusion of the cholinergic agonist carbachol caused a significant suppression of inhibitory postsynaptic potentials (IPSPs) in the pyramidal neurons that were induced by stimulation of layer Ib, with a weaker effect on IPSPs induced by stimulation of layer Ia. As previously described, carbachol also selectively suppressed excitatory postsynaptic potentials (EPSPs) elicited by intrinsic but not afferent fiber stimulation. The decrease in amplitude of IPSPs induced by layer Ib stimulation did not appear to be directly related to the decrease in EPSP amplitude induced by layer Ib stimulation. The stimulation necessary to induce neuronal firing with layer Ia stimulation was reduced in the presence of carbachol, whereas that necessary to induce neuronal firing with layer Ib stimulation was increased, despite the depolarization of resting membrane potential. Thus physiological data on cholinergic modulation of inhibitory synaptic potentials in the piriform cortex is compatible with the functional requirements determined from computational models of piriform cortex associative memory function.
Short- and Long-Term Consequences of Canal Plugging on Gaze Shifts in the Rhesus Monkey. I. Effects on Gaze Stabilization
Authors: Newlands Shawn D. , Ling Leo , Phillips James O. , Siebold Christoph , Duckert Larry , Fuchs Albert F.
Published: December 2017

Short- and long-term consequences of canal plugging on gaze shifts in the rhesus monkey. I. Effects on gaze stabilization. To study the contribution of the vestibular system to the coordinated eye and head movements of a gaze shift, we plugged the lumens of just the horizontal ( n = 2) or all six semicircular canals ( n = 1) in monkeys trained to make horizontal head-unrestrained gaze shifts to visual targets. After the initial eye saccade of a gaze shift, normal monkeys exhibit a compensatory eye counterrotation that stabilizes gaze as the head movement continues. This counterrotation, which has a gain (eye velocity/head velocity) near one has been attributed to the vestibuloocular reflex (VOR). One day after horizontal canal plugging, the gain of the passive horizontal VOR at frequencies between 0.1 and 1.0 Hz was <0.10 in the horizontal-canal-plugged animals and zero in the all-canal-plugged animal. One day after surgery, counterrotation gain was ∼0.3 in the animals with horizontal canals plugged and absent in the animal with all canals plugged. As the time after plugging increased, so too did counterrotation gain. In all three animals, counterrotation gain recovered to between 0.56 and 0.75 within 80–100 days. The initial loss of compensatory counterrotation after plugging resulted in a gaze shift that ended long after the eye saccade and just before the end of the head movement. With recovery, the length of time between the end of the eye saccade and the end of the gaze movement decreased. This shortening of the duration of reduced gain counterrotation occurred both because head movements ended sooner and counterrotation gain returned to 1.0 more rapidly relative to the end of the eye saccade. Eye counterrotation was not due to activation of pursuit eye movements as it persisted when gaze shifts were executed to extinguished targets. Also counterrotation was not due simply to activation of neck receptors because counterrotation persisted after head movements were arrested in midflight. We suggest that the neural signal that is used to cause counterrotation in the absence of vestibular input is an internal copy of the intended head movement.
Effects of Tilt of the Gravito-Inertial Acceleration Vector on the Angular Vestibuloocular Reflex During Centrifugation
Authors: Wearne Susan , Raphan Theodore , Cohen Bernard
Published: December 2017

Effects of tilt of the gravito-inertial acceleration vector on the angular vestibuloocular reflex during centrifugation. Interaction of the horizontal linear and angular vestibuloocular reflexes (lVOR and aVOR) was studied in rhesus and cynomolgus monkeys during centered rotation and off-center rotation at a constant velocity (centrifugation). During centered rotation, the eye velocity vector was aligned with the axis of rotation, which was coincident with the direction of gravity. Facing and back to motion centrifugation tilted the resultant of gravity and linear acceleration, gravito-inertial acceleration (GIA), inducing cross-coupled vertical components of eye velocity. These components were upward when facing motion and downward when back to motion and caused the axis of eye velocity to reorient from alignment with the body yaw axis toward the tilted GIA. A major finding was that horizontal time constants were asymmetric in each monkey, generally being longer when associated with downward than upward cross coupling. Because of these asymmetries, accurate estimates of the contribution of the horizontal lVOR could not be obtained by simply subtracting horizontal eye velocity profiles during facing and back to motion centrifugation. Instead, it was necessary to consider the effects of GIA tilts on velocity storage before attempting to estimate the horizontal lVOR. In each monkey, the horizontal time constant of optokinetic after-nystagmus (OKAN) was reduced as a function of increasing head tilt with respect to gravity. When variations in horizontal time constant as a function of GIA tilt were included in the aVOR model, the rising and falling phases of horizontal eye velocity during facing and back to motion centrifugation were closely predicted, and the estimated contribution of the compensatory lVOR was negligible. Beating fields of horizontal eye position were unaffected by the presence or magnitude of linear acceleration during centrifugation. These conclusions were evaluated in animals in which the low-frequency aVOR was abolished by canal plugging, isolating the contribution of the lVOR. Postoperatively, the animals had normal ocular counterrolling and horizontal eye velocity modulation during off-vertical axis rotation (OVAR), suggesting that the otoliths were intact. No measurable horizontal eye velocity was elicited by centrifugation with angular accelerations ≤40°/s2and angular velocities ≤400°/s. We conclude that in rhesus and cynomolgus monkeys, differences between horizontal eye velocities recorded during facing and back to motion constant velocity centrifugation can be explained by orienting effects of the GIA tilt on the time constants of the horizontal aVOR and not by a superposed lVOR.
Effects of Red Nucleus Microstimulation on the Locomotor Pattern and Timing in the Intact Cat: A Comparison With the Motor Cortex
Authors: Rho Marie-Josée , Lavoie Sylvain , Drew Trevor
Published: December 2017

Effects of red nucleus microstimulation on the locomotor pattern and timing in the intact cat: a comparison with the motor cortex. To determine the extent to which the rubrospinal tract is capable of modifying locomotion in the intact cat, we applied microstimulation (cathodal current, 330 Hz; pulse duration 0.2 ms; maximal current, 25 μA) to the red nucleus during locomotion. The stimuli were applied either as short trains (33 ms) of impulses to determine the capacity of the rubrospinal tract to modify the level of electromyographic (EMG) activity in different flexors and extensors at different phases of the step cycle or as long trains (200 ms) of pulses to determine the effect of the red nucleus on cycle timing. Stimuli were also applied with the cat at rest (33-ms train). This latter stimulation evoked short-latency (average = 11.8–19.0 ms) facilitatory responses in all of the physiological flexor muscles of the forelimb that were recorded; facilitatory responses were also common in the elbow extensor, lateral head of triceps but were rare in the physiological wrist and digit extensor, palmaris longus. Responses were still evoked in most muscles when the current was decreased to near threshold (3–10 μA). Stimulation during locomotion with the short trains of stimuli evoked shorter-latency (average = 6.0–12.5 ms) facilitatory responses in flexor muscles during the swing phase of locomotion and, except in the case of the extensor digitorum communis, evoked substantially smaller responses in stance. The same stimuli also evoked facilitatory responses in the extensor muscles during swing and produced more complex effects involving both facilitation and suppression in stance. Increasing the duration of the train to 200 ms modified the amplitude and duration of the EMG activity of both flexors and extensors but had little significant effect on the cycle duration. In contrast, whereas stimulation of the motor cortex with short trains of stimuli during locomotion had very similar effects to that of the red nucleus, increasing the train duration to 200 ms frequently produced a marked reset of the step cycle by curtailing stance and initiating a new period of swing. The results suggest that whereas both the motor cortex and the red nucleus have access to the interneuronal circuits responsible for controlling the structure of the EMG activity in the step cycle, only the motor cortex has access to the circuits responsible for controlling cycle timing.
Current Clamp and Modeling Studies of Low-Threshold Calcium Spikes in Cells of the Cat’s Lateral Geniculate Nucleus
Authors: Zhan X. J. , Cox C. L. , Rinzel J. , Sherman S. Murray
Published: December 2017

Current clamp and modeling studies of low-threshold calcium spikes in cells of the cat’s lateral geniculate nucleus. All thalamic relay cells display a voltage-dependent low-threshold Ca2+ spike that plays an important role in relay of information to cortex. We investigated activation properties of this spike in relay cells of the cat’s lateral geniculate nucleus using the combined approach of current-clamp intracellular recording from thalamic slices and simulations with a reduced model based on voltage-clamp data. Our experimental data from 42 relay cells showed that the actual Ca2+ spike activates in a nearly all-or-none manner and in this regard is similar to the conventional Na+/K+ action potential except that its voltage dependency is more hyperpolarized and its kinetics are slower. When the cell’s membrane potential was hyperpolarized sufficiently to deinactivate much of the low-threshold Ca2+ current ( I T) underlying the Ca2+ spike, depolarizing current injections typically produced a purely ohmic response when subthreshold and a full-blown Ca2+ spike of nearly invariant amplitude when suprathreshold. The transition between the ohmic response and activated Ca2+ spikes was abrupt and reflected a difference in depolarizing inputs of <1 mV. However, activation of a full-blown Ca2+ spike was preceded by a slower period of depolarization that was graded with the amplitude of current injection, and the full-blown Ca2+ spike activated when this slower depolarization reached a sufficient membrane potential, a quasithreshold. As a result, the latency of the evoked Ca2+ spike became less with stronger activating inputs because a stronger input produced a stronger depolarization that reached the critical membrane potential earlier. Although Ca2+ spikes were activated in a nearly all-or-none manner from a given holding potential, their actual amplitudes were related to these holding potentials, which, in turn, determined the level of I T deinactivation. Our simulations could reproduce all of the main experimental observations. They further suggest that the voltage-dependent K+ conductance underlying I A, which is known to delay firing in many cells, does not seem to contribute to the variable latency seen in activation of Ca2+ spikes. Instead the simulations indicate that the activation of I T starts initially with a slow and graded depolarization until enough of the underling transient (or T) Ca2+ channels are recruited to produce a fast, “autocatalytic” depolarization seen as the Ca2+spike. This can produce variable latency dependent on the strength of the initial activation of T channels. The nearly all-or-none nature of Ca2+ spike activation suggests that when a burst of action potentials normally is evoked as a result of a Ca2+ spike and transmitted to cortex, this signal is largely invariant with the amplitude of the input activating the relay cell.
Dynamic Representation of Eye Position in the Parieto-Occipital Sulcus
Authors: Nakamura K. , Chung H. H. , Graziano M.S.A. , Gross C. G.
Published: December 2017

Dynamic representation of eye position in the parieto-occipital sulcus. Area V6A, on the anterior bank of the parieto-occipital sulcus of the monkey brain, contains neurons sensitive both to visual stimulation and to the position and movement of the eyes. We examined the effects of eye position and eye movement on the activity of V6A neurons in monkeys trained to saccade to and fixate on target locations. Forty-eight percent of the neurons responded during these tasks. The responses were not caused by the visual stimulation of the fixation light because extinguishing the fixation light had no effect. Instead the neurons responded in relation to the position of the eye during fixation. Some neurons preferred a restricted range of eye positions, whereas others had more complex and distributed eye-position fields. None of these eye-related neurons responded before or during saccades. They all responded postsaccadically during fixation on the target location. However, the neurons did not simply encode the static position of the eyes. Instead most (88%) responded best after the eye saccaded into the eye-position field and responded significantly less well when the eye made a saccade that was entirely contained within the eye-position field. Furthermore, for many eye-position cells (45%), the response was greatest immediately after the eye reached the preferred position and was significantly reduced after 500 ms of fixation. Thus these neurons preferentially encoded the initial arrival of the eye into the eye-position field rather than the continued presence or the movement of the eye within the eye-position field. Area V6A therefore contains a representation of the position of the eye in the orbit, but this representation appears to be dynamic, emphasizing the arrival of the eye at a new position.
Effects of BDNF and NT-3 on Development of Ia/Motoneuron Functional Connectivity in Neonatal Rats
Authors: Seebach Bradley S. , Arvanov Viktor , Mendell Lorne M.
Published: December 2017

Effects of BDNF and NT-3 on development of Ia/motoneuron functional connectivity in neonatal rats. The effects of neurotrophin administration and neurotrophin removal via administration of tyrosine kinase (trk) immunoadhesins (trk receptor extracellular domains fused with IgG heavy chain) on the development of segmental reflexes were studied in neonatal rats. Brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), trkB-IgG, and trkC-IgG were delivered via subcutaneous injection on days 0, 2, 4, and 6 of postnatal life. Electrophysiological analysis of EPSPs recorded intracellularly in L5 motoneurons in response to stimulation of dorsal root L5 was carried out on postnatal day 8 in the in vitro hemisected spinal cord. Treatment with BDNF resulted in smaller monosynaptic EPSPs with longer latency than those in controls. EPSP amplitude became significantly larger when BDNF was sequestered with trkB-IgG, suggesting that BDNF has a tonic action on the development of this synapse in neonates. Treatment with NT-3 resulted in larger EPSPs, but the decrease noted after administration of trkC-IgG was not significant. Neurotrophins had little effect on the response to high-frequency dorsal root stimulation or on motoneuron properties. Polysynaptic components were exaggerated in BDNF-treated rats and reduced after NT-3 compared with controls. As in control neonates the largest monosynaptic EPSPs in NT-3 and trkB-IgG-treated preparations were observed in motoneurons with relatively large values of rheobase, probably those that are growing the most rapidly. We conclude that supplementary NT-3 and BDNF administered to neonates can influence developing Ia/motoneuron synapses in the spinal cord but with opposite net effects.
Acute Repair of Crushed Guinea Pig Spinal Cord by Polyethylene Glycol
Authors: Shi Riyi , Borgens Richard B.
Published: December 2017

Acute repair of crushed guinea pig spinal cord by polyethylene glycol. We have studied the responses of adult guinea pig spinal cord white matter to a standardized compression within a sucrose gap recording chamber. This injury eliminated compound action potential (CAP) conduction through the lesion, followed by little or no recovery of conduction by 1 h postinjury. We tested the ability of polyethylene glycol (PEG) to repair the injured axons and restore physiological function. Local application of PEG (1,800 MW, 50% by weight in water) for ∼2 min restored CAP conduction through the injury as early as 1 min post PEG application. The recovery of the CAP ≤1 h was significantly greater in treated compared with control spinal cords (controls = 3.6% of the preinjury amplitude; PEG treated = 19%; P < 0.0001, unpaired Student’s t-test). Stimulus-response analysis indicated that the susceptibility for recovery was similar for all calibers of axons after PEG application. The enhanced recovery of conduction after PEG treatment was associated with an early alteration in conduction properties relative to control spinal cords. This included increased refractoriness and sensitivity to potassium channel blockade using 4-aminopyridine (4-AP). Normally 4-AP enhanced the amplitude of the recovering CAPs by ∼40% in control spinal cords; however this effect was nearly doubled to ∼72% in PEG treated spinal cords. Because severe clinical injuries to the spinal cord (and some peripheral nerves) are both resistant to medical treatment and usually produced by compression, we discuss the possible clinical benefits of PEG application.
Effects of Spaceflight on Rhesus Quadrupedal Locomotion After Return to 1G
Authors: Recktenwald Matthew R. , Hodgson John A. , Roy Roland R. , Riazanski Sergey , McCall Gary E. , Kozlovskaya Inessa , Washburn David A. , Fanton John W. , Edgerton V. Reggie
Published: December 2017

Effects of spaceflight on Rhesus quadrupedal locomotion after return to 1G. Locomotor performance, activation patterns of the soleus (Sol), medial gastrocnemius (MG), vastus lateralis (VL), and tibialis anterior (TA) and MG tendon force during quadrupedal stepping were studied in adult Rhesus before and after 14 days of either spaceflight (n = 2) or flight simulation at 1G ( n = 3). Flight simulation involved duplication of the spaceflight conditions and experimental protocol in a 1G environment. Postflight, but not postsimulation, electromyographic (EMG) recordings revealed clonus-like activity in all muscles. Compared with preflight, the cycle period and burst durations of the primary extensors (Sol, MG, and VL) tended to decrease postflight. These decreases were associated with shorter steps. The flexor (TA) EMG burst duration postflight was similar to preflight, whereas the burst amplitude was elevated. Consequently, the Sol:TA and MG:TA EMG amplitude ratios were lower following flight, reflecting a “flexor bias.” Together, these alterations in mean EMG amplitudes reflect differential adaptations in motor-unit recruitment patterns of flexors and extensors as well as fast and slow motor pools. Shorter cycle period and burst durations persisted throughout the 20-day postflight testing period, whereas mean EMG returned to preflight levels by 17 days postflight. Compared with presimulation, the simulation group showed slight increases in the cycle period and burst durations of all muscles. Mean EMG amplitude decreased in the Sol, increased in the MG and VL, and was unchanged in the TA. Thus adaptations observed postsimulation were different from those observed postflight, indicating that there was a response unique to the microgravity environment, i.e., the modulations in the nervous system controlling locomotion cannot merely be attributed to restriction of movement but appear to be the result of changes in the interpretation of load-related proprioceptive feedback to the nervous system. Peak MG tendon force amplitudes were approximately two times greater post- compared with preflight or presimulation. Adaptations in tendon force and EMG amplitude ratios indicate that the nervous system undergoes a reorganization of the recruitment patterns biased toward an increased recruitment of fast versus slow motor units and flexor versus extensor muscles. Combined, these data indicate that some details of the control of motor pools during locomotion are dependent on the persistence of Earth’s gravitational environment.
Recruitment Order Among Motoneurons From Different Motor Nuclei
Authors: Sokoloff Alan J. , Siegel Sondra G. , Cope Timothy C.
Published: December 2017

Recruitment order among motoneurons from different motor nuclei. The principles by which motoneurons (MNs) innervating different multiple muscles are organized into activity are not known. Here we test the hypothesis that coactivated MNs belonging to different muscles in the decerebrate cat are recruited in accordance with the size principle, i.e., that MNs with slow conduction velocity (CV) are recruited before MNs with higher CV. We studied MN recruitment in two muscle pairs, the lateral gastrocnemius (LG) and medial gastrocnemius (MG) muscles, and the MG and posterior biceps femoris (PBF) muscles because these pairs are coactivated reliably in stretch and cutaneous reflexes, respectively. For 29/34 MG-LG pairs of MNs, the MN with lower CV was recruited first either in all trials (548/548 trials for 22 pairs) or in most trials (225/246 trials for 7 pairs), whether the MG or the LG MN in a pair was recruited first. Intertrial variability in the force thresholds of MG and LG MNs recruited by stretch was relatively low (coefficient of variation = 18% on average). Finally, punctate stimulation of the skin over the heel recruited 4/4 pairs of MG-LG MNs in order by CV. By all of these measures, recruitment order is as consistent among MNs from these two ankle muscles as it is for MNs supplying the MG muscle alone. For MG-PBF pairings, the MN with lower CV was recruited first in the majority of trials for 13/24 pairs and in reverse order for 9/24 pairs. The recruitment sequence of coactive MNs supplying the MG and PBF muscles was, therefore, random with respect to axonal conduction velocity and not organized as predicted by the size principle. Taken together, these findings demonstrate for the first time, that the size principle can extend beyond the boundaries of a single muscle but does not coordinate all coactive muscles in a limb.
Effects of Osmotic Stress on Dextran Diffusion in Rat Neocortex Studied With Integrative Optical Imaging
Authors: Tao Lian
Published: December 2017

Effects of osmotic stress on dextran diffusion in rat neocortex studied with integrative optical imaging. This study investigated how dextran ( M r = 3,000) diffused in rat cortical slices when the osmolarity of the bathing artificial cerebrospinal fluid was altered by varying the NaCl content. The apparent diffusion coefficient, D*, was measured in the neocortex region using fluorescent molecules and the integrative optical imaging (IOI) method. The main results were: 1) the value of D* in rat neocortex in the isotonic (300 mOsm) artificial cerebrospinal fluid at 34°C was D* = 0.68 ± 0.01 × 10−6cm2 s−1 (mean ± SE, n = 78) and it could be changed within minutes by varying the extracellular osmolarity. 2) Hypotonic stresses up to −100 mOsm decreased D* by 35% and were fully reversible when the slices were returned to the isotonic medium. Further hypotonic stress to −150 mOsm caused further decrease in D* but after removal of the stress, D* overshot its control value. 3) Hypertonic stress of +50 mOsm increased D*, but the maximum reversible increase in D* was only 15%. Further hypertonic stress (to +200 mOsm) did not cause any further increase in D* and, after removal of the stress, D* undershot the control value. The changes in D* are thought to be related to volume changes of cells in tissue: hypotonic solutions caused cell swelling, resulting in reduced extracellular space and compressed extracellular matrix so that the dextran diffusion was more hindered. Hypertonic solutions had the opposite effect. Recordings of extracellular field potentials in the hippocampal CA1 region demonstrated that, on return to the isotonic solution after exposure to an extreme hypotonic or hypertonic stress, the neurons retained their ability to generate synaptic responses.
Do Arm Postures Vary With the Speed of Reaching?
Authors: Nishikawa Kiisa C. , Murray Sara T. , Flanders Martha
Published: December 2017

Do arm postures vary with the speed of reaching? For reaching movements in one plane, the hand has been observed to follow a similar path regardless of speed. Recent work on the control of more complex reaching movements raises the question of whether a similar “speed invariance” also holds for the additional degrees of freedom. Therefore we examined human arm movements involving initial and final hand locations distributed throughout the three-dimensional (3D) workspace of the arm. Despite this added complexity, arm kinematics (summarized by the spatial orientation of the “plane of the arm” and the 3D curvature of the hand path) changed very little for movements performed over a wide range of speeds. If the total force (dynamic + quasistatic) had been optimized by the control system (e.g., as in a minimization of the change in joint torques or the change in muscular forces), the optimal solution would change with speed; slow movements would reflect the minimal antigravity torques, whereas fast movements would be more strongly influenced by dynamic factors. The speed-invariant postures observed in this study are instead consistent with a hypothesized optimization of only the dynamic forces.
Enhanced NR2A Subunit Expression and Decreased NMDA Receptor Decay Time at the Onset of Ocular Dominance Plasticity in the Ferret
Authors: Roberts Elizabeth B. , Ramoa Ary S.
Published: December 2017

Enhanced NR2A subunit expression and decreased NMDA receptor decay time at the onset of ocular dominance plasticity in the ferret. The NMDA subtype of glutamate receptor is known to exhibit marked changes in subunit composition and functional properties during neural development. The prevailing idea is that NMDA receptor–mediated synaptic responses decrease in duration after the peak of cortical plasticity in rodents. Accordingly, it is believed that shortening of the NMDA receptor–mediated current underlies the developmental reduction of ocular dominance plasticity. However, some previous evidence actually suggests that the duration of NMDA receptor currents decreases before the peak of plasticity. In the present study, we have examined the time course of NMDA receptor changes and how they correlate with the critical period of ocular dominance plasticity in the visual cortex of a highly binocular animal, the ferret. The expression of NMDA receptor subunits NR1, NR2A, and NR2B was examined in animals ranging in age from postnatal day 16 to adult using Western blotting. Functional properties of NMDA receptors in layer IV cortical neurons were studied using whole cell patch-clamp techniques in an in vitro slice preparation of ferret primary visual cortex. We observed a remarkable increase in NR1 and NR2A, but not NR2B, expression after eye opening. The NMDA receptor–mediated synaptic currents showed an abrupt decrease in decay time concurrent with the increase in NR2A subunit expression. Importantly, these changes occurred in parallel with increased ocular dominance plasticity reported in the ferret. In conclusion, molecular changes leading to decreased duration of the NMDA receptor excitatory postsynaptic current may be a requirement for the onset, rather than the end, of the critical period of ocular dominance plasticity.
Rostrocaudal Progression in the Development of Periodic Spontaneous Activity in Fetal Rat Spinal Motor Circuits In Vitro
Authors: Nakayama Kiyomi , Nishimaru Hiroshi , Iizuka Makito , Ozaki Shigeru , Kudo Norio
Published: December 2017

Rostrocaudal progression in the development of periodic spontaneous activity in fetal rat spinal motor circuits in vitro. Developmental changes in the periodic spontaneous bursts in cervical and lumbar ventral roots (VRs) were investigated using isolated spinal cord preparations obtained from rat fetuses at embryonic days ( E) 13.5–18.5. Spontaneous bursts were observed in the cervical VR at E13.5–17.5, and in the lumbar VR at E14.5–17.5. Bursts occurrence in the cervical and lumbar VRs was correlated in a 1:1 fashion at E14.5–16.5. The bursts in the cervical VR preceded those in the lumbar VR at E14.5, but the latter came to precede the former by E16.5. The interval between spontaneous bursts in the lumbar VR was greatly prolonged after spinal cord transection at the midthoracic level at E14.5, whereas that in the cervical VR became significantly longer at E14.5–16.5. These results suggest that the dominant neuronal circuit initiating the spontaneous bursts shifts from cervical to lumbar region during this period. Bath application of a glutamate receptor antagonist, kynurenate (4 mM), had little effect on the spontaneous bursts in either cervical or lumbar VRs at E14.5–15.5. At E16.5, kynurenate abolished the spontaneous bursts in the cervical VR. Concomitant application of kynurenate and strychnine (5 μM), a glycine receptor antagonist, abolished all spontaneous bursts, suggesting that the major transmitter mediating the spontaneous bursts changes from glycine to glutamate in the cervical region by E16.5, but not in the lumbar region during this period.
Neural Organization From the Superior Colliculus to Motoneurons in the Horizontal Oculomotor System of the Cat
Authors: Izawa Y. , Sugiuchi Y. , Shinoda Y.
Published: December 2017

Neural organization from the superior colliculus to motoneurons in the horizontal oculomotor system of the cat. The neural organization of the superior colliculus (SC) projection to horizontal ocular motoneurons was analyzed in anesthetized cats using intracellular recording and transneuronal labeling. Intracellular responses to SC stimulation were analyzed in lateral rectus (LR) and medial rectus (MR) motoneurons and internuclear neurons in the abducens nucleus (AINs). LR motoneurons and AINs received excitation from the contralateral SC and inhibition from the ipsilateral SC. The shortest excitation (0.9–1.9 ms) and inhibition (1.4–2.4 ms) were mainly disynaptic from the SC and were followed by tri- and polysynaptic responses evoked with increasing stimuli or intensity. All MR motoneurons received excitation from the ipsilateral SC, whereas none of them received any short-latency inhibition from the contralateral SC, but some received excitation. The latency of the ipsilateral excitation in MR motoneurons (1.7–2.8 ms) suggested that this excitation was trisynaptic via contralateral AINs, because conditioning SC stimulation spatially facilitated trisynaptic excitation from the ipsilateral vestibular nerve. To locate interneurons mediating the disynaptic SC inputs to LR motoneurons, last-order premotor neurons were labeled transneuronally after injecting wheat germ agglutinin–conjugated horseradish peroxidase into the abducens nerve, and tectoreticular axon terminals were labeled after injecting dextran-biotin into the ipsilateral or contralateral SC in the same preparations. Transneuronally labeled neurons were mainly distributed ipsilaterally in the paramedian pontine reticular formation (PPRF) rostral to retrogradely labeled LR motoneurons and the vestibular nuclei, and contralaterally in the paramedian pontomedullary reticular formation (PPMRF) caudomedial to the abducens nucleus and the vestibular nuclei. Among the last-order premotor neuron areas, orthogradely labeled tectoreticular axon terminals were observed only in the PPRF and the PPMRF contralateral to the injected SC and seemed to make direct contacts with many of the labeled last-order premotor neurons in the PPRF and the PPMRF. These morphological results confirmed that the main excitatory and inhibitory connections from the SC to LR motoneurons are disynaptic and that the PPRF neurons that receive tectoreticular axon terminals from the contralateral SC terminate on ipsilateral LR motoneurons, whereas the PPMRF neurons that receive tectoreticular axon terminals from the contralateral SC terminate on contralateral LR motoneurons.
Effects of ω-Agatoxin IVA, a P-Type Calcium Channel Antagonist, on the Development of Spinal Neuronal Hyperexcitability Caused by Knee Inflammation in Rats
Authors: Nebe Johannes , Ebersberger Andrea , Vanegas Horacio , Schaible Hans-Georg
Published: December 2017

Effects of ω-agatoxin IVA, a P-type calcium channel antagonist, on the development of spinal neuronal hyperexcitability caused by knee inflammation in rats. Both N- and P-type high-threshold calcium channels are located presynaptically in the CNS and are involved in the release of transmitters. To investigate the importance of P-type calcium channels in the generation of inflammation-evoked hyperexcitability of spinal cord neurons, electrophysiological recordings were made from wide-dynamic-range neurons with input from the knee joint in the anesthetized rat. The responses of each neuron to innocuous and noxious pressure onto the knee and the ankle were continuously assessed before and during the development of an inflammation in the knee joint induced by the injections of K/C into the joint cavity. The specific antagonist at P-type calcium channels ω-agatoxin was administered into a 30-μl trough on the spinal cord surface above the recorded neuron. In most neurons the application of ω-agatoxin before induction of inflammation slightly enhanced the responses to pressure onto the knee and ankle or left them unchanged. Two different protocols were then followed. In the control group (13 rats) only Tyrode was administered to the spinal cord during and after induction of inflammation. In these neurons the responses to mechanical stimuli applied to both the inflamed knee and to the noninflamed ankle showed a significant increase over 4 h. In the experimental group (12 rats) ω-agatoxin was applied during knee injection and in five 15-min periods up to 180 min after kaolin. This prevented the increase of the neuronal responses to innocuous pressure onto the knee and to innocuous and noxious pressure onto the ankle; only the responses to noxious pressure onto the knee were significantly enhanced during development of inflammation. Thus the development of inflammation-evoked hyperexcitability was attenuated by ω-agatoxin, and this suggests that P-type calcium channels in the spinal cord are involved in the generation of inflammation-evoked hyperexcitability of spinal cord neurons. Finally, when ω-agatoxin was administered to the spinal cord 4 h after the kaolin injection, i.e., when inflammation-evoked hyperexcitability was fully established, the responses to innocuous and noxious pressure onto the knee were reduced by 20–30% on average. The shift in the effect of ω-agatoxin, from slight facilitation or no change of the responses before inflammation to inhibition in the state of hyperexcitability, indicates that P-type calcium channels are important for excitatory synaptic transmission involved in the maintenance of inflammation-evoked hyperexcitability.
Serotonergic Modulation of Synapses in the Developing Gerbil Lateral Superior Olive
Authors: Fitzgerald Kent K. , Sanes Dan H.
Published: December 2017

Serotonergic modulation of synapses in the developing gerbil lateral superior olive. The lateral superior olive (LSO) is a primary site of binaural convergence that responds selectively to changes in interaural level difference (ILD) by integrating ipsilateral excitatory and contralateral inhibitory inputs. The circuit matures during the first three postnatal weeks, undergoing several structural and functional changes that are influenced by afferent activity. Therefore modulation of synaptic activity by neuromodulators may participate in the maturation of this circuit. The present study describes robust effects of serotonin (5-HT) on LSO synaptic function. Using whole cell voltage-clamp recording from gerbil LSO neurons (postnatal days 6–13) in an in vitro slice preparation, we have identified several distinct forms of serotonergic modulation of spontaneous and evoked synaptic transmission. First, 1–2 min application of 5-HT (100 μM) activated prolonged bursts of spontaneous inhibitory postsynaptic currents (IPSCs). However, there was an age-dependent decline, such that this effect rarely was observed beyond postnatal day 8. 5-HT apparently increased the excitability of inhibitory afferents, because 5-HT-induced IPSCs were blocked by tetrodotoxin. A second effect of 5-HT was to depress rapidly and profoundly the amplitude of electrically evoked excitatory postsynaptic currents (EPSCs). In contrast, 5-HT also depressed evoked IPSCs but to a significantly lesser degree. The receptor subtypes mediating these effects were examined using specific 5-HT agonists and antagonists. A 5-HT1 agonist, 5-carboxamidotryptamine, produced EPSC depression but did not induce spontaneous IPSCs. A 5-HT2agonist, α-Me-5-HT, reproduced all the observed effects of 5-HT (PSC depression as well as induction of spontaneous IPSCs), whereas a 5-HT2 antagonist, ketanserin, blocked the induction of spontaneous IPSCs. Therefore induction of spontaneous IPSCs is mediated by 5-HT2 receptors, whereas both 5-HT1 and 5-HT2 receptor types contribute to PSC depression. Serotonergic modulation of LSO synapses may have consequences for both developmental plasticity and auditory function. Serotonergic induction of IPSCs was observed primarily in young animals and thus may represent a mechanism for amplifying the activity of inhibitory synapses in LSO during a period of use-dependent plasticity in postnatal development. PSC depression, which preferentially affects excitation, is a potential mechanism for modulation of ILD tuning.
Unmyelinated Afferents Constitute a Second System Coding Tactile Stimuli of the Human Hairy Skin
Authors: Vallbo Å. B. , Olausson H. , Wessberg J.
Published: December 2017

Unmyelinated afferents constitute a second system coding tactile stimuli of the human hairy skin. Impulses were recorded from unmyelinated afferents innervating the forearm skin of human subjects using the technique of microneurography. Units responding to innocuous skin deformation were selected. The sample ( n = 38) was split into low-threshold units ( n = 27) and high-threshold units ( n = 11) on the basis of three distinctive features, i.e., thresholds to skin deformation, size of response to innocuous skin deformation, and differential response to sharp and blunt stimuli. The low-threshold units provisionally were denoted tactile afferents on the basis of their response properties, which strongly suggest that they are coding some feature of tactile stimuli. They exhibited, in many respects, similar functional properties as described for low-threshold C-mechanoreceptive units in other mammals. However, a delayed acceleration, not previously demonstrated, was observed in response to long-lasting innocuous indentations. It was concluded that human hairy skin is innervated by a system of highly sensitive mechanoreceptive units with unmyelinated afferents akin to the system previously described in other mammals. The confirmation that the system is present in the forearm skin and not only in the face area where it first was identified suggests a largely general distribution although there are indications that the tactile C afferents may be lacking in the very distal parts of the limbs. The functional role of the system remains to be assessed although physiological properties of the sense organs invite to speculations that the slow tactile system might have closer relations to limbic functions than to cognitive and motor functions.
Turning Strategies During Human Walking
Authors: Hase K. , Stein R. B.
Published: December 2017

Turning strategies during human walking. The mechanisms involved in rapidly turning during human walking were studied. Subjects were asked to walk at a comfortable speed and to turn toward the instructed direction as soon as they felt an electrical stimulus to the superficial peroneal nerve. Stimuli were presented repeatedly at random over 10- to 15-min periods of walking for turning in both directions. Electromyograms (EMGs), joint angular movements of the right leg, and forces under both feet were recorded. The step cycle was divided into 16 parts, and the responses to stimuli in each part were analyzed separately. Two turning strategies were used, depending on which leg was placed in front for braking. For example, to turn to the right when the right foot was placed in front, subjects generally altered direction by spinning the body around the right foot (spin turn). To turn left when the right foot was in front, subjects shifted weight to the right leg, externally rotated the left hip, stepped onto the left leg, and continued turning until the right leg stepped in the new direction (step turn). The step turn is easy and stable because the base of support during the turn is much wider than in the spin turn, so some subjects used it in all parts of the cycle. Initially, the deceleration of walking is similar to a rapid stopping task, which has been previously examined. The deceleration mechanism involves a sequence of distal-to-proximal activation of muscles on one side of the body (soleus, biceps femoris, and erector spinae). This pattern is similar to the “ankle strategy” used in postural control during forward sway. The control of foot placement in the swing leg and muscle activities for rotating the trunk in the stance leg occurred within a step after the cue. The action of ankle inverters and elevation of the pelvis by activity of gluteus medius may contribute to the control of trunk rotation. This activity was closely related to the timing of the opposite foot strike, independent of the part of the step cycle when the stimulus was applied. In most subjects, the turn was completed without resetting the underlying walking rhythm. This first EMG analysis of rapid turning shows how common strategies for postural sway and stopping can be combined with one of two turning strategies. This simplifies the complex task of turning at a random time in the step cycle.
Long-Range Inhibition Within the Zebra Finch Song Nucleus RA Can Coordinate the Firing of Multiple Projection Neurons
Authors: Spiro John E. , Dalva Matthew B. , Mooney Richard
Published: December 2017

Long-range inhibition within the zebra finch song nucleus RA can coordinate the firing of multiple projection neurons. The zebra finch forebrain song control nucleus RA (robust nucleus of the archistriatum) generates a phasic and temporally precise neural signal that drives vocal and respiratory motoneurons during singing. RA’s output during singing predicts individual notes, even though afferent drive to RA from the song nucleus HVc is more tonic, and predicts song syllables, independent of the particular notes that comprise the syllable. Therefore RA’s intrinsic circuitry transforms neural activity from HVc into a highly precise premotor output. To understand how RA’s intrinsic circuitry effects this transformation, we characterized RA interneurons and projection neurons using intracellular recordings in brain slices. RA interneurons fired fast action potentials with steep current-frequency relationships and had small somata with thin aspinous processes that extended throughout large portions of the nucleus; the similarity of their fine processes to those labeled with a glutamic acid decarboxylase (GAD) antibody strongly suggests that these interneurons are GABAergic. Electrical stimulation revealed that RA interneurons receive excitatory inputs from RA’s afferents, the lateral magnocellular nucleus of the anterior neostriatum (LMAN) and HVc, and from local axon collaterals of RA projection neurons. To map the functional connections that RA interneurons make onto RA projection neurons, we focally uncaged glutamate, revealing long-range inhibitory connections in RA. Thus these interneurons provide fast feed-forward and feedback inhibition to RA projection neurons and could help create the phasic pattern of bursts and pauses that characterizes RA output during singing. Furthermore, selectively activating the inhibitory network phase locks the firing of otherwise unconnected pairs of projection neurons, suggesting that local inhibition could coordinate RA output during singing.