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Biomedical subjects

R E Poppele

Publications and source records attributed to R E Poppele.

At least 19 recordsLinked to original sources

On the form of the internal model for reaching.

We investigated, by using simulations, possible mechanisms responsible for the errors in the direction of arm movements exhibited by deafferented patients. Two aspects of altered feedforward control were evaluated: the inability to sense initial conditions and the degradation of an internal model. A simulation which assumed no compensation for variations in initial arm configuration failed to reproduce the characteristic pattern of errors. In contrast, a simulation that assumed random variability in the generation of joint torque resulted in a distribution of handpaths which resembled some aspects of the pattern of errors exhibited by deafferented patients.

Arm

Sensory integration by the dorsal spinocerebellar tract circuitry.

Monosynaptic connections from sensory receptors to the dorsal spinocerebellar tract are believed to have a significant role in the transmission of sensory information to the cerebellum. However, predominant polysynaptic connections with highly convergent afferent input suggest a functional organization based on integrated sensory representations. We explored this possibility by examining the responses of dorsal spinocerebellar tract neurons to inputs from muscle receptors. We compared results from two sets of experiments designed to activate receptors in the gastrocnemius-soleus muscles. In one set (135 cells) we stimulated muscle receptors by stretching the isolated muscles and in the other set (194 cells) the muscle receptors were activated by passive foot flexion, which concurrently activated cutaneous and joint receptors as well. Population responses of the spinocerebellar neurons were quite different for the two types of stimuli. Foot flexion elicited long-latency excitatory responses in a majority (53%) of the cells, while muscle stretch elicited a large fraction of early peaking excitatory responses (28%) and inhibitory responses (38%). The long-latency responses to flexion could not be accounted for by specific cutaneous inputs or by possible delayed reflex contractions. We concluded that both types of population response resulted from the muscle stretch and therefore the responses of dorsal spinocerebellar tract cells to these stimuli do not simply reflect the activity in specific classes of sensory receptors.

Animals

Broad directional tuning in spinal projections to the cerebellum.

1. Spinocerebellar neurons that project in the dorsal spinocerebellar tract (DSCT) receive mono- and polysynaptic inputs from specific sensory receptors in the hindlimb, and they project mossy fiber terminals to the cerebellar vermis. We examined the functional organization of these neurons and found that it relates to whole-limb parameters like limb posture and direction of limb movement. 2. We recorded the activity of 444 DSCT units during passive perturbations of the hind foot in anesthetized cats. The movements were either confined a single joint (the ankle; 234 cells) or involved the entire hindlimb (210 cells). The cells exhibited opposite responses for opposite directions of whole-limb movement, but a variety of response patterns for opposite directions of movement at one joint. We interpret the result to imply that the population encodes information about the whole limb rather than single joints. 3. Most of the 78 neurons recorded during passive limb placements (63%) responded to changes in limb length and also changes in limb orientation. In fact, the activity of most of the cells was broadly tuned with respect to the direction of passive limb movements generated by moving the hind foot in the sagittal plane. Changes in unit activity could be described by a cosine tuning function with respect to foot positions (72% of responses) and directions of foot movement (50%). 4. The similarity of this behavior to that of neurons in the motor cortex and cerebellar nuclei recorded during voluntary movements is consistent with a common neural code to represent the sensorimotor parameters of limb movement.

Animals

Parallel distributed network characteristics of the DSCT.

1. We examined the functional organization of the dorsal spinocerebellar tract (DSCT) and found that it is similar to that of a parallel distributed network having widespread connectivity among parallel elements. The prevailing view is that the DSCT provides receptor-specific information to the cerebellum regarding muscle and cutaneous inputs from the hindlimbs, but that view does not consider the convergent inputs to DSCT neurons from multimodal polysynaptic pathways. 2. Spontaneously active DSCT neurons respond to peripheral stimulation with changes in their firing probability. We characterized the temporal patterns of poststimulus excitability changes for a large number of neurons using principal component analysis. The response of each neuron was represented by a response vector in three-dimensional principal component space, in which similar vectors represent responses having a similar waveform for their poststimulus activity patterns. 3. We compared the responses of large populations of DSCT units to two types of stimuli: small (3-8 deg) passive rotations of the foot at the ankle of an intact limb (234 cells) and stretch or contraction of an isolated muscle group (gastrocnemius-soleus, 168 cells). Most of the cells tested had significant responses (P < 0.05) to both types of stimuli (40-78% responded to muscle stimulation and 88% to foot rotation), and they exhibited similar patterns of poststimulus activity. Long-lasting inhibitory responses and excitatory responses with a range of peak times (< 10- > 60 ms) were prevalent in all cases. The population response to each stimulus was characterized by the relative incidence of response types among the units in a representative sample of the population. 4. The time course of excitability changes induced in DSCT cells by the stimuli could have been determined primarily by the presynaptic circuitry or by postsynaptic factors intrinsic to the DSCT cells. The evidence presented suggests that the selection of response waveforms and their distribution among the DSCT cells was determined presynaptically. We found that individual cells were capable of diverse responses to different stimuli. 5. Sample groups of 7-30 cells were selected at random and also on the basis of the similarity of their responses to one type of stimulus. The distributions of response types among the cells of the sample groups were compared to the distributions for the entire population recorded for each stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Origin of cuneate projections to the anterior and posterior lobes of the rat cerebellum.

The present study was carried out to analyze the topography of projections from external cuneate nucleus to the anterior and posterior lobes of the cerebellum and to investigate whether projections to the two lobes come from different cuneocerebellar neurons or from branching axons of the same cells. We used retrograde double-labeling techniques to estimate the incidence of cuneocerebellar neurons projecting to both anterior and posterior lobes via axon collaterals. Cells sending their axons to the lobus anterior were about twice the number of those projecting to the posterior lobe. The double-labeled cells were about 1/7 of all labeled neurons and were located mainly in the more lateral half of the nucleus. Therefore, the two lobes of the cerebellum are likely to receive common information from these cells, but different information from the separate populations of cuneocerebellar neurons that project only to one lobe or the other.

Animals

Origin of spinal projections to the anterior and posterior lobes of the rat cerebellum.

The present study was carried out to analyze the topography of spinal projections to the anterior and posterior lobes of the cerebellum and to investigate whether projections to the two lobes come from different spinocerebellar neurons or from branching axons of the same cells. We used orthograde transport of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) to identify the cerebellar areas where spinocerebellar axons terminate and retrograde double-labeling techniques to estimate the incidence of spinocerebellar neurons projecting to both anterior and posterior lobes via axon collaterals. Orthograde labeling confirmed that the rat, like other mammalian species, has spinocerebellar projections to two different regions of cerebellar cortex, i.e., lobules I-V of the anterior lobe and lobule VIII of the posterior lobe, with the highest incidence in lobules II, III, and VIII. We did not observe a clear difference in the distribution of afferents coming from different spinal segments to either of the two lobes. The double-labeled cells were located primarily in the lower thoracic and upper lumbar segments, almost exclusively in Clarke's column and in the dorso-lateral part of lamina 7 (in the region of the spinal border cells). It is likely that most or all of the spinocerebellar neurons in these structures project to both anterior and posterior lobes. Therefore, the two lobes of the cerebellum are likely to receive common information from these cells, but different information from the separate populations of spinocerebellar neurons that project only to one lobe or the other.

Afferent Pathways

Parallel processing of multisensory information concerning self-motion.

Cats trained to stand on a platform exhibit postural responses to dynamic tilting that appear to be based on an internal reference model of body geometry and the environment rather than directly on sensory inputs, as in a classical reflex chain. The data presented show an independent control of global variables of limb geometry, the length and the orientation, resulting from a parallel processing of multisensory inputs into separate central representations of body tilt. Limb length and orientation changes have completely different response dynamics and can be decoupled by appropriate manipulation of sensory information about self-motion.

Animals

Components of the dynamic response of mammalian muscle spindles that originate in the sensory terminals.

One component of the dynamic response of muscle spindles is characterized by a phase lead and frequency dependent sensitivity in response to sinusoidal stretches at frequencies around 1 Hz. Possible mechanisms producing this component, designated the "mid-frequency" dynamics, were investigated by testing the hypotheses that they arise from the mechanical behavior of the intrafusal muscle and alternatively from within the sensory terminals. Destruction of the myofibrillar structure of the intrafusal muscle fibers did not alter the mid-frequency dynamics, indicating that they do not arise from viscoelastic properties of the intrafusal muscle. An Arrhenius plot of the temperature dependence of the mid-frequency dynamics yielded an equivalent activation energy of 6.5 Kcal/M in the temperature range 23-42 degrees C and a 3-fold higher activation energy at lower temperatures. These observations are consistent with a dynamic process associated with a membrane-bound biochemical process. The addition of Ca++ and Ca(++)-activated-K+ (K(Ca] channel blockers (ZnCl2, Apamin and TEA) to the bathing solution altered the response dynamics by reducing the mid-frequency phase lead. The results suggest a negative feedback on the membrane potential generated by K+ efflux following a Ca++ influx that opens K(Ca) channels. A quantitative model fit to the experimental data yields a time constant of about 80 ms representing the limiting process associated with activation of the K(Ca) channels in this system. The results indicate that the mechanism underlying the mid-frequency dynamics includes at least two processes: one, not identified in this study, generates the phase lead and another, involving Ca++ and K(Ca) channels, provides a negative feedback that modifies the phase lead.

Animals

Twitch relaxation of the cat soleus muscle at different lengths and temperatures.

We recorded isometric and isotonic twitches, in situ, from the cat soleus at various muscle lengths and temperatures. At a given temperature the duration of isometric twitches increased approximately 60% for each 10% increase in muscle length, which was primarily owing to decreases in the rate of relaxation. For the relaxation of isometric twitches recorded at different muscle lengths, the equivalent activation energies determined were the same (13.2 +/- 0.3 kcal/M). The duration of isotonic twitch contractions increased only 20% for each 10% increase in muscle length. Even a small amount of shortening (3%) diminished the dependence of twitch duration on muscle length. In this case, twitch duration increased approximately 30% for every 10% increase in muscle length. Hence, even small changes in internal and/or external compliance (eg, changes in the tendon-fiber continuity) can greatly influence twitch duration. Our findings are consistent with the hypotheses that in the cat soleus, Ca2+ sequestration is primarily governed by a single energy dependent process and that the Ca2+ sensitivity of the contractile apparatus increases with increasing sarcomere length.

Animals

Electrical 'tuning' in muscle spindle receptors.

A variety of mechanical and electrical mechanisms have been shown to tune sensory receptors to selected stimuli. This study demonstrates the presence of electrical tuning in the mammalian muscle spindle. Apamin and tetraethyl ammonium ions (TEA), blockers of Ca2+-activated K+ channels, and ZnCl2, a Ca2+ channel blocker, were shown to change the dynamic behavior of the muscle spindle. We conclude that a Ca2+-activated K+ channel in the sensory nerve of the spindle provides negative feedback which alters its dynamic behavior tending to compensate for muscle dynamics. This mechanism is similar to that found in sensory hair cells in the cochlea and vestibule and may represent a general strategy for tuning in sensory receptors.

Action Potentials

Components of the responses of a population of DSCT neurons determined from single-unit recordings.

1. Impulse activity of single units belonging to the dorsal spinocerebella tract (DSCT) was recorded in response to electrical stimulation of peripheral muscle nerves at group I intensities. The responses for 187 units were determined using a spike train analysis technique that facilitates the comparison of poststimulus response time course across units (response probability function, RPF; 16). 2. The poststimulus changes in impulse activity were represented in the waveform of the RPF. Principal component analysis was used to determine the component waveforms that were common to the responses across units. The analysis showed that there were a few waveforms that dominated the majority of the responses (85% of the total variability was accounted for by five principal component waveforms). 3. A cluster analysis based on three principal component waveforms revealed seven major groups of responses according to the patterns of their poststimulus activity. These response types were composed of different combinations of short- or long-latency excitation and inhibition. The same clusters were formed regardless of response amplitude or the source of the stimulus. 4. The responses were characterized by three general features, revealed by the first three principal components. The primary feature was the sign of the response, either mostly excitatory or inhibitory. The second feature was a distinction between a short- (up to 15 ms) and long- (approximately 30 ms) latency to peak response, and the third feature was the appearance of two separate phases of opposite sign in some of the responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Components of responses of a population of DSCT neurons to muscle stretch and contraction.

1. Impulse activity of 264 units of the dorsal spinocerebellar tract (DSCT) was recorded during random contraction or stretch in hindlimb muscles. Contractions were evoked in either the isolated gastrocnemius-soleus (GS) muscles or the intact limb during crossed-extensor reflexes; stretches were applied to the isolated GS. 2. The time course of poststimulus changes in spike activity of DSCT neurons was determined from the response probability function (RPF; Ref. 15). These data were analyzed using principal component and cluster analysis to group the responses according to the RPF waveforms. 3. The responses to each type of stimulus displayed a remarkable similarity in time course, regardless of the type of stimulus used. The responses were also similar to those observed previously during single shock nerve stimulation (14). 4. The most reasonable explanation for these results is that the time course of excitability changes in DSCT neurons is determined less by particular types of receptors or patterns of afferent fiber activity than by the circuitry and afferent pathways impinging on the neurons of the DSCT. 5. The functional organization of DSCT suggested by these results includes a wide divergence from sensory receptors along polysynaptic pathways to DSCT neurons and considerable convergence onto each neuron from a diversity of receptors. Individual DSCT cells may respond to stimuli with one of a few stereo-typical response patterns yet the distribution of those patterns among the units of the DSCT population may be unique for each stimulus.

Animals

A method for determining the primary effect of a stimulus in tonically firing neurons using spike train analysis.

We present a novel method for measuring changes in the timing of spikes evoked by a stimulus in single neurons. The result provides an unambiguous separation of the stimulus effect from effects due to intrinsic spike train patterns. This separation facilitates the comparison of responses in different neurons. The analysis is based only on the spike train and requires no models of the underlying cell behavior.

Action Potentials

The extent of polysynaptic responses in the dorsal spinocerebellar tract to stimulation of group I afferent fibers in gastrocnemius-soleus.

We investigated the extent of the distribution of polysynaptic connections to the dorsal spinocerebellar tract (DSCT). Recording from a randomly selected population of DSCT units, we found that over 60% responded to maximal stimulation of group I afferent fibers in the gastrocnemius-soleus muscle nerve. Most of the responses had a time course or latency consistent with polysynaptic activation. The extensive distribution of this input into the pool of DSCT neurons suggests that input from muscle nerves in general is widely distributed to these neurons. The results further imply that the DSCT plays a more integrative role in the transmission of information from the hindlimb to the cerebellum than has been previously supposed.

Afferent Pathways

Effect of intrafusal muscle mechanics on mammalian muscle spindle sensitivity.

Sensitivity differences between primary and secondary endings of mammalian muscle spindles under various conditions of stretch and fusimotor activation may be due to differences in their respective mechanoelectric transducers or to mechanical properties of the intrafusal muscle supporting those endings. This study of isolated cat muscle spindles examines the strain in individual intrafusal muscle fibers resulting from stretch and fusimotor stimulation. The degree of local stretch occurring at the sensory endings under these conditions was measured. The results support the hypothesis that the sensitivities of primary and secondary endings are quite similar. They are directly related to the local stretch of the underlying muscle which may be altered by changes in muscle stress and stiffness.

Animals

Post-tetanic hyperpolarization evoked by depolarizing pulses in crayfish stretch receptor neurones in tetrodotoxin.

A post-tetanic hyperpolarization (p.t.h.) that is quantitatively identical to that evoked by a train of action potentials in stretch receptor neurones of crayfish Procambarus clarki and Pacifastacus leniculus is evoked when the normal Na+ influx is blocked with tetrodotoxin (TTX) and a train of depolarizing pulses is used to simulate a train of action potentials. The p.t.h. evoked by depolarizing pulses in the presence of TTX is attributable to an electrogenic Na-K pump, because it (a) is abolished by strophanthidin, (b) is abolished by removal of external K+, (c) depends in magnitude on internal Na+ concentration, (d) is not associated with a change in membrane conductance and (e) does not exhibit a reversal potential. When each action potential in the stimulus train is followed by a hyperpolarizing pulse, generation of the p.t.h. is prevented even though the action potentials are unchanged. The time constant for build-up of the p.t.h. is longer than the time constant of decay. Increasing the magnitude of depolarizing pulses increases the magnitude of the p.t.h. response in the presence of TTX and also increases the time constant for its build-up. The suppression of the p.t.h. occurring in low external Na+ appears to represent a response to a change in internal Na+ concentration, characterized by a time constant much longer than the decay of the p.t.h. The activity of the pump appears to be regulated by two mechanisms: a Na+-sensitive mechanism with a time constant of the order of a minute and an apparently voltage-sensitive mechanism with a time constant of about 5 s. The hypothesis is proposed that changes in the transmembrane electric field influence the enzymatic systems of the pump and disrupt the steady-state distribution of conformation states. The decay of the p.t.h. represents a relaxation back to the resting distribution.

Action Potentials

Cross-correlation analysis of the response of units in the dorsal spinocerebellar tract (DSCT) to muscle stretch and contraction.

Activity of DSCT units was cross-correlated with stimuli evoking gastrocnemius-soleus muscle stretch or contraction in order to investigate the muscle receptor input to DSCT. The most potent stimulus was generally muscle contraction, and the most common response one of inhibition. The similarity in response of many units to stretch, contraction and nerve simulation suggests that Golgi tendon organs are prominent source of input to DSCT, and that much of this input is inhibitory.

Action Potentials

On the application of systems analysis to neurophysiological problems.

In this essay we have presented some personal viewpoints on the application of Systems. Analysis to suitable neurophysiological problems and provided reasoned reviews on selected topics (receptor and nerve cell physiology, motor control, vestibular and visual systems) in which new data and ideas were brought about in the past several years by the use of Systems Analysis. Since the nature of the paper precludes the possibility of writing a summary, we simply thank those readers who have endured up to this point. As for those prudent persons who are beginning from this summary, before deciding as to the advisability of taking-up the task, we have a simple advice which runs contrary to the rule stated by the King to Alice in Wonderland (and accepted by one of us; see p. 60): begin from the topic that you like most and eventually go on, using the same criteria, till you are tired: then stop.

Animals