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A D McClellan

Publications and source records attributed to A D McClellan.

At least 37 records · Page 2Linked to original sources
PubMed1994

Coupling of spinal locomotor networks in larval lamprey revealed by receptor blockers for inhibitory amino acids: neurophysiology and computer modeling.

1. Receptor blockers for inhibitory amino acids were applied to part or all of the spinal cord of larval lamprey during brain stem-initiated locomotor activity. Blocking glycinergic inhibition with strychnine applied to the entire spinal cord converted the locomotor pattern from left-right alternation to synchronous left-right bursting. The results suggest that left and right oscillators are connected by relatively strong reciprocal inhibitory (glycinergic) connections in parallel with weaker reciprocal excitatory connections. This possible organization was supported by results from a computer model consisting of left and right oscillators connected by reciprocal inhibition and excitation in parallel. In addition, the results suggest that reciprocal inhibition is not required for left-right rhythmicity but rather is involved primarily with phasing of left-right activity. 2. Locally blocking glycinergic inhibition with strychnine in the rostral spinal cord resulted in synchronous left-right burst activity in that region of the cord as well as in more caudal areas of the cord in which reciprocal inhibition should still be functional. 3. Blocking glycinergic inhibition in the caudal spinal cord converted the pattern in that region of the cord to left-right synchronous activity. The effects in the ascending direction on the burst patterns in more rostral areas of the spinal cord were less than those mentioned above in the descending direction with application of strychnine to the rostral spinal cord. 4. With glycinergic inhibition or GABAergic inhibition blocked in the entire spinal cord, stable longitudinal coupling along the spinal cord persisted. This and the neurophysiology results mentioned above suggest that the main mechanism for longitudinal coupling between locomotor networks in adjacent regions of the spinal cord is ipsilateral excitatory connections and not crossed inhibitory connections. This possible organization was supported by results from a computer model, which consisted of a pair of oscillators in the more rostral and more caudal spinal cord that could be connected by various types of coupling schemes. 5. The neurophysiological data above suggest that ipsilateral, excitatory coupling is stronger in the descending direction than in the ascending direction. In the computer model, a dominant descending coupling is a necessary requirement to produce positive longitudinal phase lags.

Animals↗
PubMed1993

Time course of anatomical regeneration of descending brainstem neurons and behavioral recovery in spinal-transected lamprey.

In larval lamprey 4 weeks after a spinal transection locomotor patterns were usually complete along the body in whole animals. In in vitro preparations locomotor activity was restricted to a few millimeters below the transection. Retrograde labeling indicated that descending axons from a few brainstem neurons had grown through the transection site and probably directly activate the rostral spinal locomotor networks, but no direct descending projections were found to the caudal spinal cord. Thirty-two weeks after spinal transection locomotor activity was recorded at long distances below the transection in both whole animals and in vitro preparations. The number of brainstem neurons projecting to the rostral spinal cord below the transection appeared near normal while there was a reduced but significant projection to the caudal spinal cord. Thus, at long recovery times it appears that regenerated descending axons can directly activate the motor networks in both the rostral and caudal spinal cord and initiate locomotor activity, as is the case in normal animals.

Animals↗
PubMed1993

Time course of locomotor recovery and functional regeneration in spinal-transected lamprey: kinematics and electromyography.

The time course of recovery of locomotor function was examined with kinematic analysis and muscle recordings in larval lampreys 2-32 weeks after rostral spinal cord transection at the level of the third gill (approximately 10% of body length, BL). Animals began to recover locomotor movements within 2-4 weeks of spinal cord transection, but the amplitude of locomotor movements in the tail region was less than in normal animals. At 2 weeks post-transection, locomotor activity was limited to 20% BL, and at 3 weeks after spinal transection activity could be recorded at least as far as 40% BL. At 4 weeks after spinal transection, well-coordinated locomotor muscle activity was often present as far as 60% BL. At 8 weeks of recovery and longer, well-coordinated locomotor activity was present consistently at least as far as 60% BL, and the amplitudes of locomotor movements were restored to normal values. At each recovery time examined the ranges of locomotor parameters (cycle time, burst proportion, and intersegmental phase lag) overlapped with those in normal animals. Thus, the gradual recovery of the amplitude of locomotor movements in the caudal body is associated with the gradual return of coordinated muscle activity at progressively more caudal levels along the body. The mechanisms responsible for this gradual recovery of locomotor function are discussed in relation to our recent anatomical and in vitro studies.

Animals↗
PubMed1993

Mechanosensory inputs to the central pattern generators for locomotion in the lamprey spinal cord: resetting, entrainment, and computer modeling.

1. Mechanoreceptors in the lamprey spinal cord have inputs to the central pattern generator (CPG) for locomotion. In the present study, imposed sinusoidal and pulsed movements were applied to the end of the in vitro lamprey spinal cord to excite the mechanoreceptors so that the relationship between entrainment and resetting of the locomotor rhythm could be examined. 2. The range over which the locomotor rhythm could be entrained by sinusoidal movements was asymmetric and occurred mostly at movement cycle times below the resting cycle time. During entrainment at the shortest cycle times, the movement phases were relatively small. 3. The phase response curves (PRCs) displayed the greatest shortening of cycle times (phase advance) for movement pulses applied during the first half of the locomotor cycle, whereas movement pulses applied during the second half of the cycle were largely ineffective. The amplitude of phase shifts in the PRC correlated with the ranges of cycle times over which entrainment occurred. 4. During resetting from movement pulses applied early in the cycle, the burst and interburst parts of the cycle shortened by about the same percentage. In addition, resetting effects occurred simultaneously along the spinal cord, suggesting a rapid distribution of timing information. 5. A computer model of the CPGs, consisting of left and right oscillators and inputs from mechanosensory elements, produced entrainment ranges that were symmetric around the resting cycle time. The PRCs from the model showed phase advance for movement pulses applied during the first half of the cycle and phase delay for pulses applied during the second half of the cycle. 6. Because of the asymmetric experimental PRCs for the lamprey spinal cord, gating was incorporated into the cooffter model such that oscillators on one side of the model gated inputs from mechanosensory elements on the same side. With gating, the model produced entrainment ranges that were asymmetric and confined to cycle times below the resting cycle time. The PRCs still showed phase advance for pulses applied at the beginning of the cycle, and the amount of phase delay produced during the second half of the cycle was substantially reduced compared with the simulations without gating.

Animals↗
PubMed1992

Functional regeneration and recovery of locomotor activity in spinally transected lamprey.

Spinally transected lamprey recovery locomotor function within 3-6 weeks, and recovery is due, in part, to functional regeneration of neural pathways in the central nervous system (CNS). Our data demonstrate for the first time in the lamprey that descending axons arising from brainstem command neurons can functionally regenerate and restore locomotor initiation below a healed spinal transection site. Immediately after behavioral recovery (3-6 weeks) the locomotor pattern was incomplete but returned to normal during the remainder of the recovery period (6-40 weeks). Initially, the extent of regeneration of descending axons was limited but increased to at least 30-50 mm at recovery times of 24-40 weeks. Regenerated giant Muller axons do not contribute significantly to recovery of locomotor function; rather, regenerated axons of smaller reticulospinal neurons appear to restore locomotor initiation. The restoration of locomotor coordination across a spinal lesion is dependent on two mechanisms: regeneration of spinal coordinating neurons and mechanosensory inputs. Comparisons are made to spinal cord regeneration in other lower vertebrates and to the relative lack of CNS regeneration and behavioral recovery in higher vertebrates.

Animals↗
PubMed1990

Locomotor recovery in spinal-transected lamprey: role of functional regeneration of descending axons from brainstem locomotor command neurons.

In spinal-transected lampreys, locomotor function is restored within a few weeks, and a number of mechanisms could potentially contribute to behavioral recovery. The present study examines the contribution of functional regeneration of descending axons from brainstem locomotor "command" centers to behavioral recovery using both whole animal and in vitro preparations. Under in vitro conditions activation of brainstem locomotor centers could elicit locomotor patterns below a healed transection of the rostral spinal cord. Additional experiments indicated that spinal locomotor networks below a spinal transection could be directly activated by descending axons arising from brainstem neurons. In contrast, mechanosensory inputs and regenerated spinal neurons did not contribute significantly to the initiation of locomotor activity below a spinal lesion. Regenerated descending axons from large reticulospinal Muller neurons did not contribute significantly to the recovery of locomotor function. These results suggest that functional regeneration of descending axons from neurons in brainstem locomotor command centers contribute significantly to the recovery of locomotion following spinal cord transection. This is the first demonstration in a vertebrate of functional regeneration of descending command axons which can initiate locomotion.

Animals↗
PubMed1990

Locomotor recovery in spinal-transected lamprey: regenerated spinal coordinating neurons and mechanosensory inputs couple locomotor activity across a spinal lesion.

Larval lampreys recover locomotor function several weeks after receiving complete spinal transections. In behaviorally recovered whole-animals, the phase-coupling of locomotor activity across a lesion was similar to that observed along the body in normal, unlesioned lampreys. Two factors were found to contribute to recovery of locomotor coupling above and below a spinal transection. Firstly, under in vitro conditions regenerated spinal coordinating neurons could couple brainstem-evoked locomotor activity above and below a lesion in the absence of mechanosensory inputs. Secondly, in whole-animals mechanosensory inputs were capable of coupling locomotor activity across an acute, mid-body spinal transection in the absence of direct neural coupling through spinal coordinating neurons. Since neither regenerated coordinating neurons nor mechanosensory inputs resulted in phase-lags that were as stable as those observed in recovered whole-animals, presumably both mechanisms contribute significantly to the restoration of locomotor coupling across a healed spinal lesion.

Animals↗
PubMed1988

Brainstem command systems for locomotion in the lamprey: localization of descending pathways in the spinal cord.

The lamprey brainstem contains a 'command system' which descends into the spinal cord to activate motor networks and initiate locomotion. In the present study, partial lesions were made in the rostral spinal cord in order to spare various tracts and determine which tracts carry the descending command signal to the spinal cord. Sparing the medial areas of the rostral spinal cord usually blocked both sensory-evoked and spontaneous locomotion, while sparing the lateral regions of the rostral spinal cord did not abolish voluntary locomotor activity. Either the ventrolateral or dorsolateral spinal tracts could support the initiation of locomotion. Brainstem structures rostral to the mesencephalon were not necessary for the initiation of locomotor behavior. The data indicate that the lateral spinal tracts contain a significant part of the descending command pathway for locomotion. In contrast, the medial spinal tracts were neither necessary nor usually sufficient to support locomotor behavior, suggesting that the larger reticulospinal Muller cells, which project in these tracts, do not contribute significantly to the initiation of locomotion.

Animals↗
PubMed1988

Functional regeneration of descending brainstem command pathways for locomotion demonstrated in the in vitro lamprey CNS.

Lower vertebrates can recover locomotor function after spinal transections, and several classes of neurons in these animals can regenerate. However, no studies have directly tested for functional regeneration of descending command pathways for the initiation of locomotion in the absence of complications from sensory feedback. In the present study, the contribution of regeneration of descending command pathways to the reacquisition of locomotion was examined in behaviorally recovered, spinal-transected larval lampreys using in vitro brain/spinal cord preparations, in which mechanosensory feedback was eliminated. Activation of brainstem command centers produced locomotor activity below a healed transection site and this burst activity was coupled 1:1 with locomotor activity above the transection site. Furthermore, the parameters characterizing locomotor patterns in in vitro preparations were similar to those recorded during locomotion in normal, whole-animals. Additional experiments indicated that descending pathways from the brainstem had regenerated across the healed transection site and could directly activate spinal locomotor networks below the lesion area. These data appear to be the first direct demonstration in a vertebrate of functional regeneration of descending command pathways for the initiation of locomotion.

Action Potentials↗
PubMed1988

Features of entrainment of spinal pattern generators for locomotor activity in the lamprey spinal cord.

The in vitro lamprey spinal cord contains a "central pattern generator" (CPG) that can generate locomotor activity with excitatory amino acids added to the bath. The motor pattern can be entrained by imposed rhythmic bending of either the caudal or rostral end of the notochord/spinal cord. In the present study, the quantitative and mechanistic features of entrainment were investigated. Increasing the amplitude of the imposed movement increased the range of frequencies over which entrainment occurred. Brief, pulsed, imposed movements could reset the locomotor rhythm. During entrainment at different imposed movement frequencies, the burst duration was a constant proportion of about 35% of the cycle time. The intersegmental phase lag, which is usually constant at about 0.01 during locomotion, decreased significantly with caudal imposed movements. A small increase in the phase lags was observed with rostral imposed movements. In low-calcium Ringer's, briefly bending the notochord/spinal cord activated intraspinal mechanoreceptors and elicited ascending and descending unit activity in lateral spinal fascicles many segments from the point of bending. However, this ascending or descending movement-related activity was insufficient to fully entrain the locomotor rhythm, since blocking the pattern in the region of bending abolished 1:1 entrainment. The mechanoreceptors appear to act locally on the CPG networks, since interrupting the ascending or descending movement-related activity with lesions of the lateral fascicles did not abolish entrainment. In contrast, stripping the very lateral margins of the spinal cord in the region of bending did abolish entrainment, presumably by destroying the transduction region of the mechanoreceptors. The data, taken together, suggest that the mechanoreceptors entrain the local CPG networks, and this timing information is then distributed to the other parts of the spinal motor networks through the coordinating system.

Afferent Pathways↗
PubMed1987

In vitro CNS preparations: unique approaches to the study of command and pattern generation systems in motor control.

In vitro preparations of the nervous system, which were originally developed for investigations of invertebrate neural networks, have recently gained popularity for studying locomotor networks in the vertebrate nervous system. The nervous system is removed from the animal and maintained in a physiological bathing solution. These preparations can be induced to generate locomotor patterns in a number of ways and offer several unique advantages. The function of the motor networks can be manipulated by alterating the composition of the bath, and immobilization of the preparations, either by cutting ventral roots or bath application of curare, greatly facilitates intracellular recordings. In vitro preparations offer the opportunity to acquire the detailed information necessary for understanding vertebrate motor networks at the cellular level. This article reviews some of the many applications of in vitro preparations for studying vertebrate locomotor control using examples derived mainly from work on the lamprey.

Action Potentials↗
PubMed1985

Pharmacological activation of locomotor patterns in larval and adult frog spinal cords.

The effects of amino acids, catecholamines, and their agonists shown to elicit locomotor activity in several vertebrate species were examined in spinal animals and isolated nervous systems of developing tadpoles (Rana catesbiana) and adult frogs (R. catesbiana and pipiens). Elicited activity was correlated in spinal animals by video and electromyographic analysis, and in in vitro spinal cords by recordings of tail and hindlimb motor activity. Of the agents tested, only N-methyl-DL-aspartate (NMA), an amino acid agonist, was effective in eliciting motor activity in spinal animals. In isolated nervous systems, both NMA and D-glutamate added to the bath activated locomotor activity. NMA injected i.p. into tadpoles with high spinal cord transections elicited coordinated swimming motor activity in axial and hindlimb muscles that was roughly typical for the stage of development of the animal. In late stage tadpoles (st. XX), NMA also elicited wiping and alternating or synchronous (i.e. kicking or jumping) hindlimb movements. Addition of NMA or glutamate to a bath containing an in vitro tadpole spinal cord preparation elicited ventral root motor activity characteristic of swimming, but without a rostrocaudal phase lag. Rhythmic activity thought to underlie stepping and kicking was seen in lateral ventral rootlets innervating the hindlimbs. In adult frogs with high spinal cord transections, injection of NMA elicited a general sequence of spontaneous hindlimb motor functions: reflex wiping, stepping, and kicking or jumping. Isolated frog spinal cords were not responsive to bath applied NMA, under the present conditions. The activation by amino acids or their agonists of different motor functions in both larval and adult frogs, as well as in higher and lower vertebrates, suggests a general significance of amino acid-activated receptors in the neural networks controlling locomotor function.

2-Aminoadipic Acid↗
PubMed1984

Descending control and sensory gating of 'fictive' swimming and turning responses elicited in an in vitro preparation of the lamprey brainstem/spinal cord.

An in vitro lamprey nervous system preparation has been developed which consists of the head and exposed brainstem attached to the isolated spinal cord (resting on the notochord). Mechanical or electrical stimulation of the snout elicits motor activity in ventral roots which underlies a turning response (head withdrawal) away from the stimulus followed by escape swimming. Direct stimulation of the sensory division of the trigeminal nerve activates these patterns, and cutting this nerve abolishes ventral root activity elicited by stimulation of the snout. These patterns of ventral root activity are correlated with muscle activity and escape movements in intact animals. Sensory input activated by passive bending of the notochord/spinal cord gates the first burst in ipsilateral ventral roots during turning motor activity, and this response can thus be considered as a position dependent 'enhancement' reflex. Descending pathways activated by stimulation of the snout consist of axons which project for at least 20 segments, and are not significantly dependent on propagation through local circuits in the gray matter. The in vitro brainstem/spinal cord preparation survives for several days and will permit studies of the descending systems which normally initiate two types of motor acts, swimming and turning responses.

Animals↗
PubMed1984

Activation of 'fictive swimming' by electrical microstimulation of brainstem locomotor regions in an in vitro preparation of the lamprey central nervous system.

Electrical microstimulation of specific areas of the brainstem in an in vitro preparation of the lamprey CNS elicits coordinated swimming motor activity recorded in spinal ventral roots. Swimming motor activity could be graded in intensity by variations in stimulus current. This 'brainstem locomotor region' extends from the mesencephalon, near the torus semicircularis, caudally through the rhombencephalon in parallel strips about 200-300 micron lateral to the midline.

Adaptation, Physiological↗
PubMed1983

Initiation and sensory gating of 'fictive' swimming and withdrawal responses in an in vitro preparation of the lamprey spinal cord.

An in vitro preparation has been developed in which the caudal part of the lamprey spinal cord (resting on the notochord) is still innervating the tail fin. Mechanical stimulation of the tail fin elicits ventral root activity that would normally lead to an initial body flexure (tail fin withdrawal) followed by escape swimming. These patterns of ventral root activity are correlated with motor activity and movements elicited by a similar tail fin stimulus in intact and spinal lampreys. The ascending control systems activated by tail fin stimulation consists of long axons which project for at least 20 segments, and are not dependent on propagation through local circuits in the gray matter. Sensory input activated by passive bending of the notochord/spinal cord in the in vitro preparation gates the tail fin withdrawal motor activity, such that tail fin stimulation elicits ventral root bursts on the same side as the direction of bending. This new in vitro preparation survives for several days and will provide new opportunities to study the normal initiation and coordination of two different patterns of behavior, swimming and withdrawal.

Animals↗
PubMed1983

Higher order neurons in buccal ganglia of Pleurobranchaea elicit vomiting motor activity.

The buccal mass of the gastropod Pleurobranchaea is used during a regurgitation response that consists of a writhing phase interrupted by brief periodic bouts of a vomiting phase (17, 20). During transitions from writhing to vomiting, specific changes occur in the motor pattern (19, 20). Evidence is presented suggesting that at least some of the initiation or "command" neurons for vomiting reside in the buccal ganglia. The present paper examines the role of two candidate vomiting-initiation cells, the ventral white cells (VWC) and midganglionic cells (MC), in the buccal ganglia of isolated nervous systems. Stimulation of single VWCs activates a vomiting motor pattern, consisting in part of alternating buccal root activity. Furthermore, the VWCs fire in high-frequency bursts during episodes (i.e., bouts) of this same vomiting pattern. Mutual reexcitation between the VWCs and motor pattern generator (MPG) appears to produce the accelerated buildup and maintenance of vomiting rhythms. Brief stimulation of single MCs "triggers" bouts of a vomiting motor pattern, but the membrane potential of this cell is only modulated during this same pattern, at least in the isolated nervous system. It is proposed that in intact animals the MCs are activated by sensory inputs and briefly excite the VWC-MPG network, thereby turning on the mutual reexcitatory mechanism mentioned above and switching the output pattern. A general implication for gastropod research is that higher order neurons that activate buccal root activity cannot automatically be given the function of "feeding command neuron," as some cells clearly control other responses, such as vomiting.

Animals↗
PubMed1982

A differential displacement transducer for measuring relative movement in biological systems.

This article describes a modified and improved version of the displacement transducer design originally presented by Sandeman (1968). The present design generates a high frequency electric field in the bathing solution. Relative displacement is detected within this field by measuring the differential voltage between two small diameter wire-sensing electrodes, which can be attached to different biological structures. By placing one of the sensing electrodes at a fixed point within the bath, absolute displacement can also be measured. A brief theoretical discussion and complete design are presented for the differential displacement transducer. The method presented here is more sensitive and versatile than the original approach.

Animals↗