Journal of Neurophysiology

Huguenard, J. R.; Hamill, O. P.; Prince, D. A.

doi: N/Apmid: 2452862

Abstract 1. Na+ conductances have been characterized in rat neocortical neurons from the sensorimotor area. Neurons were obtained by acute dissociation from animals at developmental stages from embryonic day 16 (E16) to postnatal day 50 (P50) to quantify any developmental changes in the kinetic properties of the Na+ conductance. 2. Neurons were divided into two classes, based on morphology, to determine whether there are any cell-type specific differences in Na+ conductances that contribute to the different action potential morphologies seen in current-clamp recordings in vitro. 3. Upon isolation, neurons were voltage clamped using the whole-cell variation of the patch-clamp technology. Both cell types, pyramidal and nonpyramidal, demonstrate large increases in Na+ current density during this developmental period (E16-P50). Normalized conductances were near 10 pS/micron2 in neurons from embryonic animals, and increased 6- to 10-fold during the first 2 wk postnatal. The final conductance reached in pyramidal neurons was higher than in non-pyramidal neurons. 4. We found no differences between the two cell types, pyramidal and nonpyramidal, in the voltage dependence of activation, inactivation kinetics, voltage dependence of steady-state inactivation, and recovery from inactivation. 5. The time course of Na+ current in immature neurons were fit with classical Hodgkin-Huxley kinetics. However, in more mature neurons the kinetics of inactivation became more complicated such that two decay components were required to obtain good fit. The slowly decaying component had a time course 5 to 10 times slower than the fast component. 6. Several procedures were used to reduce the magnitude of Na+ conductance in mature neurons to ensure graded, voltage-dependent inward currents. These included reduced extracellular Na+, submaximal tetrodotoxin concentrations, and reduced holding potential. Under each of these conditions we were able to verify the observation that Na+ current inactivation occurs with two exponentials. 7. Single-channel Na+ currents were obtained from cell-attached patches. The membrane density of active Na+ channels increases with development, and ensemble averages from mature neurons demonstrated two inactivation processes. The slow inactivation process was accounted for by long-latency single-channel openings of the same amplitude as the short-latency openings. 8. We conclude that there are no kinetic differences in the Na+ channels between cell types. Differences in action potentials are then not explained by differences in Na+ current kinetics, but might be partially explained by the different densities.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Fournier, M.; Sieck, G. C.

doi: N/Apmid: 3367195

Abstract 1. Muscle units in the right sternocostal region of the cat diaphragm (DIA) were isolated in situ by dissecting filaments of the C5 ventral root. Isometric contractile and fatigue properties of DIA units were then measured. Contractile properties included: twitch contraction time (CT), peak twitch tension (Pt), maximum tetanic tension (P0), and the frequency dependence of tension production. Muscle-unit fatigue resistance was estimated using a 2-min fatigue test. 2. DIA muscle units were classified as fast (F) or slow (S) based on the presence or absence of sag in their unfused tetanic force responses. Muscle-unit fatigue indices (FI) were used to further classify DIA units as slow-twitch fatigue-resistant (S), fast-twitch fatigue-resistant (FR) fast-twitch fatigue-intermediate (FInt), or fast-twitch fatigable (FF) types. 3. Based on a total of 47 completely characterized DIA muscle units, 21% were classified as S, 4% as FR, 28% as FInt, and 47% as FF. In contrast to the distribution of unit types in other mixed appendicular muscles, the DIA was composed of a very low proportion of FR units and a relatively high proportion of FInt units. An interval of FIs between 0.50 and 0.75 separated units into fatigue-resistant and fatigable groups. The distribution of FIs for FF and most FInt units was continuous, indicating that they formed a single fatigable group. Relatively few FF units in the DIA had FIs less than 0.10. 4. A wide range of contractile properties was observed for DIA muscle units. Type S units had longer CTs and lower Pt and P0 values than type F units. The mean Pt and P0 of FF and FInt units were comparable, whereas the mean Pt and P0 of the two FR units were lower. Type S units produced a greater proportion of their P0 at lower frequencies of activation than type F units. The lower P0S produced by type F units in the DIA indicated that they were smaller than similar units in appendicular muscles. It was concluded that in meeting most normal ventilatory requirements, adequate force could be generated by the recruitment of only type S and FR units. The recruitment of the more fatigable FF and FInt units may occur only during more forceful respiratory and nonrespiratory behaviors of the DIA. Copyright © 1988 the American Physiological Society

Aniss, A. M.; Gandevia, S. C.; Burke, D.

doi: N/Apmid: 2966852

Abstract 1. This study was undertaken to determine whether low-threshold cutaneous and muscle afferents from mechanoreceptors in the foot reflexly affect fusimotor neurons innervating the plantar and dorsiflexors of the ankle during voluntary contractions. 2. Recordings were made from 29 identified muscle spindle afferents innervating triceps surae and the pretibial flexors. Trains of electrical stimuli (5 stimuli, 300 impulses per second) were delivered to the sural nerve at the ankle (intensity: 2-4 times sensory threshold) and to the posterior tibial nerve at the ankle (intensity: 1.5-3 times motor threshold for the small muscles of the foot). The stimuli were delivered while the subject maintained an isometric voluntary contraction of the receptor-bearing muscle, sufficient to accelerate the discharge of each spindle ending. This ensured that the fusimotor neurons directed to the ending were active and influencing the spindle discharge. The effects of these stimuli on muscle spindle discharge were assessed using raster displays, frequencygrams, poststimulus time histograms (PSTHs) and cumulative sums ("CUSUMs") of the PSTHs. Reflex effects onto alpha-motoneurons were determined from poststimulus changes in the averaged rectified electromyogram (EMG). Reflex effects of these stimuli onto single-motor units were assessed in separate experiments using PSTHs and CUSUMs. 3. Electrical stimulation of the sural or posterior tibial nerves at nonnoxious levels had no significant effect on the discharge of the 14 spindle endings in the pretibial flexor muscles. The electrical stimuli also produced no significant change in discharge of 11 of 15 spindle endings in triceps surae. With the remaining four endings in triceps surae, the overall change in discharge appeared to be an increase for two endings (at latencies of 60 and 68 ms) and a decrease for two endings (at latencies of 110 and 150 ms). The difference in the incidence of the responses of spindle endings in tibialis anterior and in triceps surae was significant (P less than 0.05, chi 2 test). 4. For both triceps surae and pretibial flexor muscles the electrical stimuli to sural or posterior tibial nerves had clear effects on the alpha-motoneuron pool, whether assessed using surface EMG or the discharge of single-motor units. Based on EMG recordings using intramuscular wire electrodes, the reflex effects differed for the gastrocnemii and soleus. 5. In this study, reflex changes in the discharge of human spindle endings were more difficult to demonstrate than comparable changes in the discharge of alpha-motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Voigt, H. F.; Young, E. D.

doi: N/Apmid: 3367194

Abstract 1. Cross-correlation analysis of simultaneously recorded spike trains can be used to gain insight into functional interactions among neurons. In this paper, we report on cross-correlation analysis of neuron pairs in the dorsal cochlear nucleus (DCN) of the cat. Neuron pairs were isolated with two independent electrodes, which allow systematic study of the effects on correlation of distances between units and differences in their best frequencies (BFs). The data in this paper were obtained from 51 pairs consisting of two neurons of the same type. 2. Cross-correlograms were obtained for 35 pairs composed of type IV units, which are recorded from the principal cells of the DCN. Pairs of type IV units with correlated activities give cross-correlograms with increased correlation near zero delay. This feature is called a central mound (CM) and most likely results from shared excitatory or shared inhibitory inputs. 3. Records of spontaneous activity were obtained from 31 pairs of type IV units. Six of these pairs have correlated spontaneous activities. All six pairs have BFs that differ by less than 0.2 octaves. The shared input inducing these correlations must be a spontaneously active and tonotopically organized projection, like the auditory nerve. Type II units, thought to be DCN inhibitory interneurons that project to type IV units, are not spontaneously active, and thus cannot be the cause of correlated spontaneous activity. Similarly, cochlear granule cells, whose axons project orthogonally to the tonotopic sheets of DCN, cannot be the cause of correlated spontaneous activity because their projection is not confined tonotopically. 4. Stimulus-driven activities were studied for 12 type IV pairs that have uncorrelated spontaneous activities. Five of these pairs have correlated driven activities, with CMs whose sizes depend on the frequency and sound level of the acoustic stimulus. A frequency vs. sound level correlation response map shows the V-shaped tuning properties of the correlation-inducing mechanism. The properties of stimulus-driven correlation in these type IV pairs are consistent with the hypothesis that the correlation is induced by shared input from DCN type II units, although this is not the only possibility. 5. All six type IV pairs with correlated spontaneous activities have correlated driven activities. In five of these pairs, the degree of correlation decreases from its value with spontaneous activity when a low-level acoustic stimulus is applied. Three of these five pairs were tested at higher stimulus levels.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Moore, L. E.; Yoshii, K.; Christensen, B. N.

doi: N/Apmid: 2835446

Abstract 1. The excitable properties of branched cells were measured using a combination of voltage-clamp and frequency-domain techniques. Point impedance functions from either the soma or growth cone of NG-108 cells were curve fitted with a reduced cable model at different membrane potentials to establish kinetic parameters. 2. Transfer impedance functions between the soma and growth cone were measured and simulated with a morphologically determined model. In these experiments the membrane potential was controlled by a single-electrode voltage clamp thus allowing an estimate of transfer functions for any arbitrary input, such as a single synaptic current for differing degrees of tonic synaptic drive. Furthermore, the integration of different regional inputs was evaluated based on the transfer functions between different locations on an individual cell. 3. The activation of an outward steady-state current leads to resonating impedance functions that were used to evaluate the kinetic properties of ionic channels in different regions of branched excitable cells. For simple branching patterns the point and transfer impedances show lower resonant frequencies for active growth cones compared with active somas. 4. More complex branching patterns showed the unexpected result that the voltage-dependent resonant frequency was higher for the growth cone recording than the soma. The presence of a higher resonant frequency when the growth cone is activated does not require more rapid kinetics of the active potassium conductance, since the time constant of the active conductance can be the same in the growth cone and the soma membrane. 5. In conclusion, the resonant frequencies, as well as all other aspects of the impedance functions, are complicated interactions of the detailed branching patterns and active conductances. In general, these interactions are not predictable from a passive electrotonic analysis, especially when the voltage-dependent conductances are distributed throughout the dendritic tree. Copyright © 1988 the American Physiological Society

Yoshii, K.; Moore, L. E.; Christensen, B. N.

doi: N/Apmid: 2835447

Abstract 1. Impulse response functions were determined from complex point impedance and transfer functions from cultured NG-108 cells to simulate the propagation of a synaptic potential in response to the release of transmitter. In general, the flow of synaptic current has a much shorter duration than the normal membrane time constant, thereby making the use of impulse response functions useful approximations to synaptic events. 2. The resonance observed during the activation of the potassium conductance was reflected in the impulse response function as a pronounced damped oscillation. A comparison of the impulse response functions calculated from point impedance and transfer functions showed similar results for current injections in the growth cone. 3. In addition to the resonance effects of the voltage-dependent conductances on transfer and impulse response functions due principally to the activation of conductances for outward currents, transfer functions were measured during the activation of a steady-state negative conductance. Under these conditions the phase function approaches 180 degrees, indicating that the voltage response is out of phase with the current. 4. In the steady state, the effect of a negative conductance is to algebraically add to the positive conductances and generally decrease the absolute conductance unless there is a net negative current. The decreased conductance enhances the impulse response and the DC space constant, thus leading to a better propagation of slow potentials. This effect can be seen as a decrease in the electrotonic length, L, with intermediate depolarizations. At large depolarizations the steady-state activation of the K conductance generally dominates and leads to a greatly increased electrotonic length. 5. Both the net conductances and the associated kinetics play a role in shaping the potential changes during a synaptic current. This is especially critical if there is a net negative steady-state conductance. Under these conditions there is a surprising reduction in the impulse response function. 6. Thus, during a subthreshold activation of the voltage-dependent negative conductances, the observable synaptic potentials would be either large potential responses due to an apparent increase in the impedance (algebraic summation of positive and negative conductances with a net positive conductance) or a minimal response because of the phasic cancellation due to a net negative conductance. The latter condition could exist near the synaptic reversal potential due to a large synaptic drive and would appear experimentally as a form of inhibition.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Huang, C. S.; Sirisko, M. A.; Hiraba, H.; Murray, G. M.; Sessle, B. J.

doi: N/Apmid: 2835448

Abstract 1. The technique of intracortical microstimulation (ICMS), supplemented by single-neuron recording, was used to carry out an extensive mapping of the face primary motor cortex. The ICMS study involved a total of 969 microelectrode penetrations carried out in 10 unanesthetized monkeys (Macaca fascicularis). 2. Monitoring of ICMS-evoked movements and associated electromyographic (EMG) activity revealed a general pattern of motor cortical organization. This was characterized by a representation of the facial musculature, which partially enclosed and overlapped the rostral, medial, and caudal borders of the more laterally located cortical regions representing the jaw and tongue musculatures. Responses were evoked at ICMS thresholds as low as 1 microA, and the latency of the suprathreshold EMG responses ranged from 10 to 45 ms. 3. Although contralateral movements predominated, a representation of ipsilateral movements was found, which was much more extensive than previously reported and which was intermingled with the contralateral representations in the anterior face motor cortex. 4. In examining the fine organizational pattern of the representations, we found clear evidence for multiple representation of a particular muscle, thus supporting other investigations of the motor cortex, which indicate that multiple, yet discrete, efferent microzones represent an essential organizational principle of the motor cortex. 5. The close interrelationship of the representations of all three muscle groups, as well as the presence of a considerable ipsilateral representation, may allow for the necessary integration of unilateral or bilateral activities of the numerous face, jaw, and tongue muscles, which is a feature of many of the movement patterns in which these various muscles participate. 6. In six of these same animals, plus an additional two animals, single-neuron recordings were made in the motor and adjacent sensory cortices in the anesthetized state. These neurons were electrophysiologically identified as corticobulbar projection neurons or as nonprojection neurons responsive to superficial or deep orofacial afferent inputs. The rostral, medial, lateral, and caudal borders of the face motor cortex were delineated with greater definition by ICMS and these electrophysiological procedures than by cytoarchitectonic features alone. We noted that there was an approximate fit in area 4 between the extent of projection neurons and field potentials anti-dromically evoked from the brain stem and the extent of positive ICMS sites.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Surmeier, D. J.; Honda, C. N.; Willis, W. D.

doi: N/Apmid: 3367200

Abstract 1. Two hundred and twenty-one spinothalamic tract (STT) neurons in the lumbar spinal cord of anesthetized monkeys were studied. The majority of the recordings were in laminae IV-VI. Thirteen of these neurons were intracellularly injected with horseradish peroxidase and histologically reconstructed. 2. A standard series of four mechanical cutaneous stimuli, which ranged in intensity from innocuous brushing to tissue-damaging pinching, were used to test the mechanical responsiveness of STT neurons. The mean alterations in discharge rate produced by these test stimuli when delivered to a neuron's excitatory receptive field were used as response measures. 3. Univariate and bivariate analyses of these response measures failed to reveal natural groupings of STT neurons. To assess whether natural groupings dependent upon shared multivariate response patterns were present, a k-means cluster analysis of the responses was performed. 4. Because an assumption about the type of coding used by the STT system had to be made prior to clustering, two independent analyses were performed. One approach assumed a labeled line coding model; response magnitudes were determined within the context of the neuron under study (within-neuron analysis). The other approach assumed a population coding model; response magnitudes were determined within the context of the STT population (across-neuron analysis). 5. The within-neuron analysis suggested that the STT sample could be partitioned into four groups. The smallest group (n = 18, 8%) responded primarily to brushing but often had a convergent nociceptive input; this group was referred to as type I. A second group (n = 31, 14%) had strong responses to low-intensity stimuli, particularly pressure, and modestly larger responses to noxious stimuli; this group was referred to as type II. The clustering in these two groups was relatively weak, reflecting some heterogeneity in response pattern. 6. The largest within-neuron group (n = 108, 49%) was most responsive to noxious stimuli but had a saturating response function; because of their apparent role in coding intermediate intensity stimuli, this group was referred to as type III. The fourth group (n = 64, 29%) responded best to the most intense stimulus used; this group was referred to as type IV. 7. The across-neuron analysis also suggested that the STT sample could be partitioned into four groups. The largest group (n = 122, 55%) had relatively weak responses to all the cutaneous stimuli; this group was referred to as type A. 8. All of the remaining across-neuron groups had mean responses at or above the mean for all cutaneous stimuli.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

May, J. G.; Keller, E. L.; Suzuki, D. A.

doi: N/Apmid: 3367205

Abstract 1. Anatomical and single-unit recording studies suggest that the dorsolateral pontine nucleus (DLPN) in monkey is a major link in the projection of descending visual motion information to the cerebellum. Such studies coupled with cortical and cerebellar lesion results suggest a major role for this basilar pontine region in the mediation of smooth-pursuit eye movements. 2. To provide more direct evidence that this pontine region is involved in the control of smooth-pursuit eye movements, focal chemical lesions were made in DLPN in the vicinity of previously recorded visual motion and pursuit-related neurons. Eye movement responses were subsequently recorded in these lesioned animals under several behavioral paradigms. 3. A major deficit in smooth-pursuit performance was produced after unilateral DLPN lesions generated either reversibly with lidocaine or more permanently with ibotenic acid. Pursuit impairments were observed during steady-state tracking of sinusoidal target motion as well as during the initiation of pursuit tracking to sudden ramp target motion. Through the use of the latter technique, initial eye acceleration was reduced to less than one-half of normal for animals with large lesions of the dorsolateral and lateral pontine nuclei. 4. The pursuit deficit in all animals was directional in nature and was not dependent on the visual hemifield in which the motion stimulus occurred. The largest effect for horizontal tracking occurred in all animals for pursuit directed ipsilateral to the lesion. Animals also showed major deficits in one or both directions of vertical pursuit, although the primary direction of the vertical impairment was variable from animal to animal. 5. Chemical lesions in the DLPN also produced comparable deficits in the initiation of optokinetic-induced smooth eye movements in the ipsilateral direction. In contrast to this effect on the initial optokinetic response, in the one lesioned animal studied during prolonged constant velocity optokinetic drum rotation, smooth eye speed increased slowly over a 10- to 15-s period to reach a level that closely matched drum speed. These results suggest that pathways outside the DLPN can generate the steady-state optokinetic response. 6. Saccades to stationary targets were normal after DLPN lesions, but corrective saccades made to targets moving in the direction ipsilateral to the lesion were much more hypometric than similar prelesion control saccades. 7. The pursuit deficits produced by lidocaine injections recovered within 30 min. The ibotenic acid deficits were maximal approximately 1 day after the injection and recovered rapidly thereafter over a time period of 3-7 days.(ABSTRACT TRUNCATED AT 400 WORDS) Copyright © 1988 the American Physiological Society

Gottlieb, G. L.; Agarwal, G. C.

doi: N/Apmid: 3367204

Abstract 1. Step changes in torque were applied to the elbow or ankle joint of normal human subjects who exerted constant levels of effort. They were instructed to not react to the torque but to allow their limbs to move to a new equilibrium position. In this experimental paradigm, the joint may be characterized by a nonlinear compliant element. The aim of this study was to characterize the elastic properties of the compliant element. 2. Joint elasticity is described by an S-shaped relation between torque and angle (a "compliant characteristic curve"). The stiffness of a joint is greatest for small perturbations and decreases as the size of the perturbation is increased whether the limb is loaded or unloaded from its initial equilibrium. 3. The S shape of the compliant characteristic curve is relatively constant when measured at different initial joint angles from the same initial joint torque. 4. Higher levels of initial muscle torque increase the steepness of the compliant characteristic curve. 5. All changes in initial joint torque and angle preserve the S shape. The inflection point of the characteristic curve is always at the initial equilibrium angle and torque. This shifting of the inflection point of the torque-angle relation implies a fundamental plasticity in joint compliance. The elastic component is not invariant but changes with the joint's initial equilibrium state. 6. Changes in muscle tension and length that result from a perturbation are accompanied by changes in muscle activation. The relationship between perturbation torque and mean equilibrium EMG is similar to that found for voluntary isometric contraction. It is not possible to conclude what proportion of the late EMG response to perturbation is mediated by segmental reflex mechanisms. 7. At the levels of torque used here, changes in joint stiffness are highly correlated with changes in tonic contraction of the muscle opposing the load. This change in stiffness is not the result of antagonist coactivation, which was minimal. 8. The compliant characteristic curves of elbow and ankle are qualitatively similar. The principal difference is due to the greater passive stiffness of the ankle. 9. Our findings are inconsistent with aspects of the theory of invariant characteristics or with models of movement and load compensation that postulate a control scheme based only on the setting of muscle and reflex equilibrium points. The data are also incompatible with models that only control the elastic stiffness of the muscle. Copyright © 1988 the American Physiological Society