Neuronal Correlates of Functional Coupling between Reach- and Grasp-Related Components of Muscle Activity.

Coordinated reach-to-grasp movements require precise spatiotemporal synchrony between proximal forelimb muscles (shoulder, elbow) that transport the hand toward a target during reach, and distal muscles (wrist, digit) that simultaneously preshape and orient the hand for grasp. The precise mechanisms through which the redundant neuromuscular circuitry coordinates reach with grasp, however, remain unclear. Recently, Geed and Van Kan (2016) demonstrated, using exploratory factor analysis (EFA), that limited numbers of global, template-like transport/preshape- and grasp-related muscle components underlie the complexity and variability of intramuscular electromyograms (EMGs) of up to 21 distal and proximal muscles recorded while monkeys performed reach-to-grasp tasks. Importantly, transport/preshape- and grasp-related muscle components showed invariant spatiotemporal coupling, which provides a potential mechanism for coordinating forelimb muscles during reach-to-grasp movements. In the present study, we tested whether ensemble discharges of forelimb neurons in the cerebellar nucleus interpositus (NI) and its target, the magnocellular red nucleus (RNm), a source of rubrospinal fibers, function as neuronal correlates of the transport/preshape- and grasp-related muscle components we identified. EFA applied to single-unit discharges of populations of NI and RNm neurons recorded while the same monkeys that were used previously performed the same reach-to-grasp tasks, revealed neuronal components in the ensemble discharges of both NI and RNm neuronal populations with characteristics broadly similar to muscle components. Subsets of NI and RNm neuronal components were strongly and significantly crosscorrelated with subsets of muscle components, suggesting that similar functional units of reach-to-grasp behavior are expressed by NI and RNm neuronal populations and forelimb muscles. Importantly, like transport/preshape- and grasp-related muscle components, their NI and RNm neuronal correlates showed invariant spatiotemporal coupling. Clinical and lesion studies have reported disruption of coupling between reach and grasp following cerebellar damage; the present results expand on those studies by identifying a neuronal mechanism that may underlie cerebellar contributions to spatiotemporal coordination of distal and proximal limb muscles during reaching to grasp. We conclude that finding similar functional units of behavior expressed at multiple levels of information processing along interposito-rubrospinal pathways and forelimb muscles supports the hypothesis that functionally related populations of NI and RNm neurons act synergistically in the control of complex coordinated motor behaviors.

Determination of the location and magnitude of synaptic conductance changes in spinal motoneurons by impedance measurements.

The relation between impedance change and the location and magnitude of a tonic synaptic conductance was examined in compartmental motoneuron models based on previously published data. The dependency of motoneuron impedance on system time constant (tau), electrotonic length (L), and dendritic-to-somatic conductance ratio (rho) was examined, showing that the relation between impedance phase and rho differed markedly between models with uniform and nonuniform membrane resistivity. Dendritic synaptic conductances decreased impedance magnitude at low frequencies; at higher frequencies, impedance magnitude increased. The frequency at which the change in impedance magnitude reversed from a decrease to an increase-the reversal frequency, F(r)-was a good estimator of electrotonic synaptic location. A measure of the average normalized impedance change at frequencies less than F(r), cuDeltaZ, estimated relative synaptic conductance. F(r) and cuDeltaZ provided useful estimates of synaptic location and conductance in models with nonuniform (step, sigmoidal) and uniform membrane resistivity. F(r) also provided good estimates of spatial synaptic location on the equivalent cable in both step and sigmoidal models. Variability in relations between F(r), cuDeltaZ, and conductance location and magnitude between neurons was reduced by normalization with rho and tau. The effects on F(r) and cuDeltaZ of noise in experimental recordings, different synaptic distributions, and voltage-dependent conductances were also assessed. This study indicates that location and conductance of tonic dendritic conductances can be estimated from F(r), cuDeltaZ, and basic electrotonic motoneuron parameters with the exercise of suitable precautions.

Location and magnitude of conductance changes produced by Renshaw recurrent inhibition in spinal motoneurons.

The mean location of Renshaw synapses on spinal motoneurons and their synaptic conductance were estimated from changes in impedance magnitude produced by sustained recurrent inhibition. Motoneuron impedance was determined by injecting quasi-white noise current into lumbosacral motoneurons of pentobarbital-anesthetized cats. Synaptic location and conductance were estimated by comparing observed impedance changes to simulation results obtained using standard motoneuron models and compartmental models fit to each impedance function. Estimated synaptic locations ranged from 0.10 to 0.41lambda, with a mean of 0.19 or 0.24lambda, depending on the estimation method. Average dendritic path length was 262 microm. Average synaptic conductance was 23 to 27 nS (range: 6.7 to 57.9 nS), corresponding to conductance changes of 78 to 88% of resting membrane conductance. Estimated accuracy was supported by consistency using different estimation methods, agreement with Fyffe's 1991 morphological data, and comparisons of observed and simulated recurrent IPSP amplitudes. Synaptic location, but not synaptic conductance, was correlated with rheobase, a measure of motoneuron excitability. Synaptic conductance did not depend on synaptic location. A regression analysis demonstrated that synaptic conductance and cell impedance were the principal factors determining recurrent IPSP amplitude. Simulations using the observed values and locations of Renshaw conductance demonstrate that recurrent inhibition can require as much as an additional 14 to 18% sustained excitatory synaptic conductance to depolarize motoneurons sufficiently to activate somatic or dendritic inward currents and recruit motoneurons or amplify excitatory synaptic currents.

Contribution of primate magnocellular red nucleus to timing of hand preshaping during reaching to grasp.

Magnocellular red nucleus (RNm) is involved in controlling goal-directed limb movements such as reaching to grasp. We tested two hypotheses related to RNm's role in controlling reach-to-grasp movements. One hypothesis is that forelimb RNm neurons are grasp specific, and the other is that they specify the timing of metacarpi-phalangeal (MCP) extension to preshape the hand during the appropriate phase of the reach. We recorded single-unit discharge while monkeys performed two behavioral tasks that elicited similar reaches but differed in grasp. One task consisted of a reach with a precision grasp that elicited independent use of thumb and forefinger; the other included a whole-hand grasp that elicited concerted use of the four fingers. Most RNm neurons tested were engaged strongly during both the whole-hand and precision tasks, and the magnitude of discharge modulation did not differ between tasks. Thus most RNm neurons are not grasp specific but, instead, may contribute to behavioral features common to the two tasks. Two methods were used to investigate relations between single-unit discharge and kinematic data from the same individual trials of the whole-hand and precision tasks for a subset of forelimb RNm neurons. One method focused on correlations between parameters of RNm discharge and the duration, amplitude, and velocity of rotation of forelimb joints for each of the tasks. The second method compared between-task differences in times of peak neuronal discharge to between-task differences in times of rotations of forelimb joints. Parameters of reach-related RNm discharge were more frequently correlated with parameters of MCP extension than with parameters of rotation of wrist, elbow, and shoulder joints. Analyses of temporal relations between discharge and kinematic data during both the whole-hand and precision tasks indicate that discharge was time locked most frequently to MCP extension and, to a lesser extent, elbow extension during both tasks. We conclude that RNm may command muscle synergies that provide a basic preshape of the hand at the appropriate phase of limb transport. In addition, the timing of RNm's contribution to hand preshaping varies with the behavioral requirements of the task.

Discharge of primate magnocellular red nucleus neurons during reaching to grasp in different spatial locations.

Reaching to grasp is of fundamental importance to primate motor behavior. One descending motor pathway that contributes to the control of this behavior is the rubrospinal tract. An important source of origin of the rubrospinal tract is the magnocellular red nucleus (RNm). Forelimb RNm neurons discharge vigorously during reach-to-grasp movements. RNm discharge is important for hand use, as coordinated whole-limb movements without hand use are not associated with strong discharge. Because RNm is functionally linked to muscles of the entire forelimb, RNm discharge may also contribute to use of the proximal limb that accompanies hand use. If RNm contributes to proximal limb use, we predict discharge to differ for reaches that differ in proximal limb involvement but require the same grasp. We tested this prediction by measuring discharge of individual RNm neurons while monkeys reached to grasp objects in four spatial locations in front of them. The animals reached from the waist to locations to the left, right, above, and below the shoulder of the "reaching" limb. RNm neurons of our sample were activated strongly during reach-to-grasp, and discharge of a third of the neurons tested depended on the spatial location of the object grasped. Discharge of RNm neurons and EMG activity of many of the distal and proximal forelimb muscles we tested were larger for reaching to grasp in the upper and/or right than lower and left target locations. Based on comparisons of each individual neuron's discharge patterns during reaches with and without preshaping the hand, we conclude that target location-dependent modulations in discharge rate of the majority of RNm neurons whose discharge differed for reaching to grasp in the four target locations contributed to aspects of hand preshaping that covaried with reach direction.