Journal of Neurophysiology

Llinás, Rodolfo R.; Steriade, Mircea

doi: 10.1152/jn.00166.2006pmid: 16554502

This article addresses the functional significance of the electrophysiological properties of thalamic neurons. We propose that thalamocortical activity, is the product of the intrinsic electrical properties of the thalamocortical (TC) neurons and the connectivity their axons weave. We begin with an overview of the electrophysiological properties of single neurons in different functional states, followed by a review of the phylogeny of the electrical properties of thalamic neurons, in several vertebrate species. The similarity in electrophysiological properties unambiguously indicates that the thalamocortical system must be as ancient as the vertebrate branch itself. We address the view that rather than simply relays, thalamic neurons have sui generis intrinsic electrical properties that govern their specific functional dynamics and regulate natural functional states such as sleep and vigilance. In addition, thalamocortical activity has been shown to be involved in the genesis of several neuropsychiatric conditions collectively described as thalamocortical dysrhythmia syndrome. Address for reprint requests and other correspondence; R. R. Llinás, 550 First Ave, NYC 10016 (E-mail: [email protected] )

Ferrera, Vincent P.; Grinband, Jack

doi: 10.1152/jn.00163.2006pmid: 16510779

Sekirnjak, Chris; Hottowy, Pawel; Sher, Alexander; Dabrowski, Wladyslaw; Litke, A. M.; Chichilnisky, E. J.

doi: 10.1152/jn.01168.2005pmid: 16436479

Existing epiretinal implants for the blind are designed to electrically stimulate large groups of surviving retinal neurons using a small number of electrodes with diameters of several hundred micrometers. To increase the spatial resolution of artificial sight, electrodes much smaller than those currently in use are desirable. In this study, we stimulated and recorded ganglion cells in isolated pieces of rat, guinea pig, and monkey retina. We used microfabricated hexagonal arrays of 61 platinum disk electrodes with diameters between 6 and 25 µm, spaced 60 µm apart. Charge-balanced current pulses evoked one or two spikes at latencies as short as 0.2 ms, and typically only one or a few recorded ganglion cells were stimulated. Application of several synaptic blockers did not abolish the evoked responses, implying direct activation of ganglion cells. Threshold charge densities were typically <0.1 mC/cm 2 for a pulse duration of 100 µs, corresponding to charge thresholds of <100 pC. Stimulation remained effective after several hours and at high frequencies. To show that closely spaced electrodes can elicit independent ganglion cell responses, we used the multielectrode array to stimulate several nearby ganglion cells simultaneously. From these data, we conclude that electrical stimulation of mammalian retina with small-diameter electrode arrays is achievable and can provide high temporal and spatial precision at low charge densities. We review previous epiretinal stimulation studies and discuss our results in the context of 32 other publications, comparing threshold parameters and safety limits. Address for reprint requests and other correspondence: E. J. Chichilnisky, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037 (E-mail: [email protected] )

Gondin, Julien; Duclay, Julien; Martin, Alain

doi: 10.1152/jn.01002.2005pmid: 16481458

The aim of the study was to use combined longitudinal measurements of soleus (SOL) and gastrocnemii evoked V-wave and H-reflex responses to determine the site of adaptations within the central nervous system induced by 5 wk of neuromuscular electrical stimulation (NMES) training of the plantar flexor muscles. Nineteen healthy males subjects were divided into a neuromuscular electrostimulated group ( n = 12) and a control group ( n = 7). The training program consisted of 15 sessions of isometric NMES over a 5-wk period. All subjects were tested before and after the 5-wk period. SOL, lateral gastrocnemius (LG), and medial gastrocnemius (MG) maximal H-reflex and M-wave potentials were evoked at rest (i.e., H max and M max , respectively) and during maximal voluntary contraction (MVC) (i.e., H sup and M sup , respectively). During MVC, a supramaximal stimulus was delivered that allowed us to record the V-wave peak-to-peak amplitudes from all three muscles. The SOL, LG, and MG electromyographic (EMG) activity as well as muscle activation (twitch interpolation technique) were also quantified during MVC. After training, plantar flexor MVC increased significantly by 22% ( P < 0.001). Torque gains were accompanied by an increase in muscle activation (+11%, P < 0.05), SOL, LG, and MG normalized EMG activity (+51, +54, and +60%, respectively, P < 0.05) and V/M sup ratios (+81, +76, and +97%, respectively, P < 0.05). H max /M max and H sup /M sup ratios for all three muscles were unchanged after training. In conclusion, the increase in voluntary torque after 5 wk of NMES training could be ascribed to an increased volitional drive from the supraspinal centers and/or adaptations occurring at the spinal level. Address for reprint requests and other correspondence: J. Gondin, INSERM ERM 207, Faculté des Sciences du Sport, BP 27877, 21078 Dijon Cedex, France (E-mail: [email protected] )

Wong, Adrian Y. C.; Billups, Brian; Johnston, Jamie; Evans, Richard J.; Forsythe, Ian D.

doi: 10.1152/jn.00694.2005pmid: 16481462

Activation of presynaptic receptors plays an important role in modulation of transmission at many synapses, particularly during high-frequency trains of stimulation. Adenosine-triphosphate (ATP) is coreleased with several neurotransmitters and acts at presynaptic sites to reduce transmitter release; such presynaptic P2X receptors occur at inhibitory and excitatory terminals in the medial nucleus of the trapezoid body (MNTB). We have investigated the mechanism of purinergic modulation during high-frequency repetitive stimulation at the calyx of Held synapse. Suppression of calyceal excitatory postsynaptic currents (EPSCs) by ATP and ATPγS (100 µM) was mimicked by adenosine application and was blocked by DPCPX (10 µM), indicating mediation by adenosine A1 receptors. DPCPX enhanced EPSC amplitudes during high-frequency synaptic stimulation, suggesting that adenosine has a physiological role in modulating transmission at the calyx. The Luciferin-Luciferase method was used to probe for endogenous ATP release (at 37°C), but no release was detected. Blockers of ectonucleotidases also had no effect on endogenous synaptic depression, suggesting that it is adenosine acting on A1 receptors, rather than degradation of released ATP, which accounts for presynaptic purinergic suppression of synaptic transmission during physiological stimulus trains at this glutamatergic synapse. Address for reprint requests and other correspondence: Professor Ian D. Forsythe, MRC Toxicology Unit, University of Leicester, Leicester, LE1 9HN. United Kingdom. (E-mail: [email protected] )

Hains, Bryan C.; Saab, Carl Y.; Waxman, Stephen G.

doi: 10.1152/jn.01009.2005pmid: 16481457

We recently showed that spinal cord contusion injury (SCI) at the thoracic level induces pain-related behaviors and increased spontaneous discharges, hyperresponsiveness to innocuous and noxious peripheral stimuli, and enlarged receptive fields in neurons in the ventral posterolateral (VPL) nucleus of the thalamus. These changes are linked to the abnormal expression of Na v 1.3, a rapidly repriming voltage-gated sodium channel. In this study, we examined the burst firing properties of VPL neurons after SCI. Adult male Sprague–Dawley rats underwent contusion SCI at the T9 level. Four weeks later, when Na v 1.3 protein was upregulated within VPL neurons, extracellular unit recordings were made from VPL neurons in intact animals, those with SCI, and in SCI animals after receiving lumbar intrathecal injections of Na v 1.3 antisense or mismatch oligodeoxynucleotides for 4 days. After SCI, VPL neurons with identifiable peripheral receptive fields showed rhythmic oscillatory burst firing with changes in discrete burst properties, and alternated among single-spike, burst, silent, and spindle wave firing modes. Na v 1.3 antisense, but not mismatch, partially reversed alterations in burst firing after SCI. These results demonstrate several newly characterized changes in spontaneous burst firing properties of VPL neurons after SCI and suggest that abnormal expression of Na v 1.3 contributes to these phenomena. Address for reprint requests and other correspondence: S. G. Waxman, Department of Neurology, LCI-707, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510 (E-mail: [email protected] )

Hamel-Pâquet, Catherine; Sergio, Lauren E.; Kalaska, John F.

doi: 10.1152/jn.00789.2005pmid: 16481461

Many single-neuron recording studies have examined the degree to which the activity of primary motor cortex (M1) neurons is related to the kinematics and kinetics of various motor tasks. This has not been explored as extensively for arm movement-related neurons in posterior parietal cortex area 5. We recorded the activity of 78 proximal arm–related neurons in area 5 of two monkeys while they used their whole arm to make reaching movements toward eight targets on a horizontal plane against an inertial load or to generate isometric forces at the hand in the same eight horizontal directions. The overall range of measured output forces was similar in the two tasks. The forces increased monotonically in the desired direction in the isometric task. In the movement task, in contrast, they showed a rapid initial increase in the direction of movement, followed by a transient reversal of forces as the hand approached the target. Many task-related area 5 neurons were tuned for the direction of motor output in the tasks, but most area 5 neurons were more strongly active or exclusively active in the movement task than in the isometric task. Furthermore, their activity at either the single cell or population level did not reflect the transient reversal of output forces during movement. In contrast, M1 neuronal activity was typically strong in both tasks and showed task-related changes that reflected the differences in the time course and directionality of force outputs between both tasks, including the transient reversal of forces in the movement task. These results show that area 5 neurons are less strongly related to the time-course of task kinetics than M1 during isometric and arm-movement tasks. Address for reprint requests and other correspondence: J. F. Kalaska, Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Faculté de Médecine, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, Québec H3C 3J7, Canada (E-mail: [email protected] )

Coxon, James P.; Stinear, Cathy M.; Byblow, Winston D.

doi: 10.1152/jn.01334.2005pmid: 16495356

Volitional inhibition is the voluntary prevention of a prepared movement. Here we ask whether primary motor cortex (M1) is a site of convergence of cortical activity associated with movement preparation and volitional inhibition. Volitional inhibition was studied by presenting a stop signal before execution of an anticipated response that requires a key lift to intercept a revolving dial. Motor evoked potentials (MEPs) were elicited in intrinsic hand muscles by transcranial magnetic stimulation (TMS) to assess corticomotor excitability and short interval intracortical inhibition (sICI) during task performance. The closer the stop cue was presented to the anticipated response, the harder it was for subjects to inhibit their response. Corticomotor pathway excitability was temporally modulated during volitional inhibition. Using subthreshold TMS, corticomotor excitability was reduced for Stop trials relative to Go trials from 140 ms after the cue. sICI was significantly greater for Stop trials compared with Go trials at a time that preceded the onset of muscle activity associated with the anticipated response. These results provide evidence that volitional inhibition is exerted at a cortical level and that inhibitory networks within M1 contribute to volitional inhibition of prepared action. Address for reprint requests and other correspondence: W. Byblow, Human Motor Control Laboratory, Tamaki Campus, University of Auckland, Private Bag 92019, Auckland, New Zealand (E-mail: [email protected] )

Shi, Riyi; Whitebone, Jim

doi: 10.1152/jn.00350.2005pmid: 16510778

White matter strips extracted from adult guinea pig spinal cords were subjected to tensile strain (stretch) injury ex vivo. Strain was carried out at three magnitudes (25, 50, and 100%) and two strain rate regimens: slow (0.006–0.008 s –1 ) and fast (355–519 s –1 ). The cord samples were monitored physiologically using a double sucrose-gap technique and anatomically using a horseradish peroxidase assay. It seems that a higher magnitude of strain inflicted significantly more functional and structural damage within each strain rate group. Likewise, a higher strain rate inflicted more damage when the strain magnitude was maintained. It is evident that axons have remarkable tolerance to strain injury at a slow strain rate. Even a 100% strain at the slow rate only eliminated two-thirds of the compound action potential amplitude and resulted in almost no membrane damage when examined 30 min after strain. It is also clear that the spontaneous recovery is evident yet not complete compared with preinjury levels at the fast strain rate. To examine the factors that might influence the vulnerability of axons to strain, we have shown that the axonal diameters did not play a significant role in dictating the susceptibility of axons to strain. Rather, it is speculated that the location of axons might be a more important factor in this regard. The knowledge gained from this study is likely to be informative in elucidating the spinal cord biomechanical response to strain and strain rate. Address for reprint requests and other correspondence: R. Shi, Center for Paralysis Research, Dept. of Medical Sciences, School of Veterinary Medicine, Purdue Univ., West Lafayette, IN 47907 (E-mail: [email protected] )

Santer, Roger D.; Rind, F. Claire; Stafford, Richard; Simmons, Peter J.

doi: 10.1152/jn.00024.2006pmid: 16452263

Flying locusts perform a characteristic gliding dive in response to predator-sized stimuli looming from one side. These visual looming stimuli trigger trains of spikes in the descending contralateral movement detector (DCMD) neuron that increase in frequency as the stimulus gets nearer. Here we provide evidence that high-frequency (>150 Hz) DCMD spikes are involved in triggering the glide: the DCMD is the only excitatory input to a key gliding motor neuron during a loom; DCMD-mediated EPSPs only summate significantly in this motor neuron when they occur at >150 Hz; when a looming stimulus ceases approach prematurely, high-frequency DCMD spikes are removed from its response and the occurrence of gliding is reduced; and an axon important for glide triggering descends in the nerve cord contralateral to the eye detecting a looming stimulus, as the DCMD does. DCMD recordings from tethered flying locusts showed that glides follow high-frequency spikes in a DCMD, but analyses could not identify a feature of the DCMD response alone that was reliably associated with glides in all trials. This was because, for a glide to be triggered, the high-frequency spikes must be timed appropriately within the wingbeat cycle to coincide with wing elevation. We interpret this as flight-gating of the DCMD response resulting from rhythmic modulation of the flight motor neuron's membrane potential during flight. This means that the locust's escape behavior can vary in response to the same looming stimulus, meaning that a predator cannot exploit predictability in the locust's collision avoidance behavior. Address for reprint requests and other correspondence: R. D. Santer, School of Biology and Psychology, Ridley Building, University of Newcastle upon Tyne, Newcastle upon Tyne, NE1 7RU, UK (E-mail: [email protected] ).