Motor Coordination Behavior Research Articles

Active listening in a complex environment

Spatially guided behaviors in echolocating bats depend upon the dynamic interplay between auditory information processing and adaptive motor control. The bat produces ultrasonic signals and uses information contained in the returning echoes to determine the direction and distance of objects in space. With this acoustic information, the echolocating bat builds a 3-D auditory representation of the world, which it uses to guide a suite of coordinated motor behaviors, including head and pinna movements, as well as the timing, duration, frequency characteristics, and directionality of sonar signals. Adaptive echolocation behaviors shape the acoustic information available to the bat’s sonar imaging system and provide a window to its perception of complex scenes. In a complex environment, an echolocating bat encounters multiple reflecting surfaces that return a cascade of echoes from each sonar transmission. The work presented here will focus on adaptive echolocation behaviors of the big brown bat as it tracks a selected prey item in the presence of multiple objects, both obstacles and other prey. Data suggest that bats can successfully segregate streams of echoes from closely spaced objects through finely tuned adaptive sonar signal control.

Climbing Fiber Input Shapes Reciprocity of Purkinje Cell Firing

The cerebellum fine-tunes motor activity via its Purkinje cell output. Purkinje cells produce two different types of spikes, complex spikes and simple spikes, which often show reciprocal activity:a periodical increase in complex spikes is associated with a decrease in simple spikes, and vice versa. This reciprocal firing is thought to be essential for coordinated motor behavior, yet how it is accomplished is debated. Here, we show in Ptf1a::cre;Robo3(lox/lox) mice that selectively rerouting the climbing fibers from a contralateral to an ipsilateral projection reversed the complex-spike modulation during sensory stimulation. Strikingly, modulation of simple spikes, which is supposed to be controlled by mossy fibers, reversed as well. Climbing fibers enforce this reciprocity in part by influencing activity of inhibitory interneurons, because the phase of their activity was also converted. Ptf1a::cre;Robo3(lox/lox) mice showed severe ataxia highlighting that climbing fiber input and its impact on reciprocity of Purkinje cell firing play an important role in motor coordination.

Odor-induced crawling locomotion in the newborn rat: Effects of amniotic fluid and milk.

Early locomotion in the neonatal rat previously has been reported 3 days after birth during exposure to an odor of biological relevance (nest material). The current study explores if other ecologically relevant stimuli-amniotic fluid (AF) and milk-could evoke a similar locomotor response in the newborn rat and whether the endogenous opioid system mediates the response. Newborn rats tested 24 hr after birth were presented with the odors of AF or milk while placed in a runway. Pups expressed crawling and moved along the runway in response to direct exposure to the odors of AF and milk (Exp. 1). However, there was no evidence that this crawling response was altered after pretreatment with the opioid antagonist naloxone (Exp. 2). This study provides evidence of the capacity of AF and milk to evoke coordinated motor behavior, suggesting that they may play a role in the development of fundamental motor patterns.

In vivo optogenetic tracing of functional corticocortical connections between motor forelimb areas

Interactions between distinct motor cortical areas are essential for coordinated motor behaviors. In rodents, the motor cortical forelimb areas are divided into at least two distinct areas: the rostral forelimb area (RFA) and the caudal forelimb area (CFA). The RFA is thought to be an equivalent of the premotor cortex (PM) in primates, whereas the CFA is believed to be an equivalent of the primary motor cortex. Although reciprocal connections between the RFA and the CFA have been anatomically identified in rats, it is unknown whether there are functional connections between these areas that can induce postsynaptic spikes. In this study, we used an in vivo Channelrhodopsin-2 (ChR2) photostimulation method to trace the functional connections between the mouse RFA and CFA. Simultaneous electrical recordings were utilized to detect spiking activities induced by synaptic inputs originating from photostimulated areas. This method, in combination with anatomical tracing, demonstrated that the RFA receives strong functional projections from layer 2/3 and/or layer 5a, but not from layer 5b (L5b), of the CFA. Further, the CFA receives strong projections from L5b neurons of the RFA. The onset latency of electrical responses evoked in remote areas upon photostimulation of the other areas was approximately 10 ms, which is consistent with the synaptic connectivity between these areas. Our results suggest that neuronal activities in the RFA and the CFA during movements are formed through asymmetric reciprocal connections.

LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors

Mutations in the LRRK2 gene are the most common cause of genetic Parkinson’s disease. Although the mechanisms behind the pathogenic effects of LRRK2 mutations are still not clear, data emerging from in vitro and in vivo models suggests roles in regulating neuronal polarity, neurotransmission, membrane and cytoskeletal dynamics and protein degradation.We created mice lacking exon 41 that encodes the activation hinge of the kinase domain of LRRK2. We have performed a comprehensive analysis of these mice up to 20 months of age, including evaluation of dopamine storage, release, uptake and synthesis, behavioral testing, dendritic spine and proliferation/neurogenesis analysis.Our results show that the dopaminergic system was not functionally comprised in LRRK2 knockout mice. However, LRRK2 knockout mice displayed abnormal exploratory activity in the open-field test. Moreover, LRRK2 knockout mice stayed longer than their wild type littermates on the accelerated rod during rotarod testing. Finally, we confirm that loss of LRRK2 caused degeneration in the kidney, accompanied by a progressive enhancement of autophagic activity and accumulation of autofluorescent material, but without evidence of biphasic changes.

A channelopathy contributes to cerebellar dysfunction in a model of multiple sclerosis

Cerebellar dysfunction in multiple sclerosis (MS) contributes significantly to disability, is relatively refractory to symptomatic therapy, and often progresses despite treatment with disease-modifying agents. We previously observed that sodium channel Nav1.8, whose expression is normally restricted to the peripheral nervous system, is present in cerebellar Purkinje neurons in a mouse model of MS (experimental autoimmune encephalomyelitis [EAE]) and in humans with MS. Here, we tested the hypothesis that upregulation of Nav1.8 in cerebellum in MS and EAE has functional consequences contributing to symptom burden. Electrophysiology and behavioral assessment were performed in a new transgenic mouse model overexpressing Nav1.8 in Purkinje neurons. We also measured EAE symptom progression in mice lacking Nav1.8 compared to wild-type littermates. Finally, we administered the Nav1.8-selective blocker A803467 in the context of previously established EAE to determine reversibility of MS-like deficits. We report that, in the context of an otherwise healthy nervous system, ectopic expression of Nav1.8 in Purkinje neurons alters their electrophysiological properties, and disrupts coordinated motor behaviors. Additionally, we show that Nav1.8 expression contributes to symptom development in EAE. Finally, we demonstrate that abnormal patterns of Purkinje neuron firing and MS-like deficits in EAE can be partially reversed by pharmacotherapy using a Nav1.8-selective blocker. Our results add to the evidence that a channelopathy contributes to cerebellar dysfunction in MS. Our data suggest that Nav1.8-specific blockers, when available for humans, merit study in MS.

Intraoperative Applications Of The H-Reflex And F-Response: A Tutorial

Traditional intraoperative monitoring of spinal cord function involves the use of three techniques: 1. Orthodromic ascending somatosensory evoked potentials (SSEPs) and 2. antIDromic descending neurogenic somatosensory evoked potentials (DNSSEPs) monitor long-tract sensory function. SSEPs and DNSSEPs do not monitor interneuronal gray matter function. 3. Transcranial motor evoked potentials (TMEPs) monitor descending long-tract motor function and measure interneuronal gray matter function by activating motor neurons. TMEPs activate from 4-5% of the motor neuron pool. When using TMEPs 95-96% of the motor spinal cord systems activating the motor neurons are not monitored. Our ability to interact with our environment involves not only intact sensation and strength, but also complex coordinated motor behavior. Complex coordinated motor behavior is controlled by groups of electrically-coupled spinal cord central pattern generators (CPGs). The components of CPGs are: descending and propriospinal systems, peripheral input, and segmental interneurons. The point-of-control is the level of excitation of interneurons, which is determined by the integrated activity of the other components. Spinal cord injury (SCI) changes segmental reflex gain by uncoupling these components. Changes in gain are detected by recordings from muscles. SSEPs, DNSSEPs and TMEPs provIDe limited information about the status of CPGs. H-reflexes measure the function of from 20-100% of the motor neuron pool. F-responses measure the function of from 1-5% of the motor neuron pool. H-reflexes and F-responses provIDe information about the degree of coupling between CPG components. Recording H-reflexes and F-responses together with SSEPs and TMEPs not only monitors spinal cord long-tract function, but also provIDes a multiple-systems approach that monitors those spinal cord systems that are responsible for the control of complex coordinated motor behavior. The objective of this paper is to describe how H-reflexes and F-responses can be used to monitor complex coordinated motor behavior.

Preserved implicit form perception and orientation adaptation in visual form agnosia

Visual form agnosia is mainly characterized by profound deficits in visual form and shape discrimination. Previous studies have shown that patients retain the capacity for coordinated motor behaviors, color naming and implicit letter perception. However, it is unknown to what extent other visual functions, such as implicit form and orientation perception, are preserved. To address these questions, we investigated a single visual form agnosic patient, X.F., in two distinct experiments. X.F.'s visual lesions were mainly localized in the bilateral occipitotemporal cortex, with the dorsal visual stream and early visual cortex largely spared. In Experiment 1, X.F. named the color of different forms across 12 blocks of trials. After the first six blocks, the combinations of a form with its color were changed and the new combination was presented for the remaining six blocks. X.F.'s reaction time increased during the switch block and was significantly greater than the overall RT changes between adjacent, non-switch blocks. This indicates that X.F. retained the ability to perceive changes in form despite her inability to discriminate the forms. In Experiment 2, X.F. showed selective orientation adaptation effects to different spatial frequencies; that is, her contrast threshold was significantly higher when the adapting and test orientations were the same than when they were orthogonal, although her orientation discrimination performance was severely impaired. These data provide evidence of a functional dissociation between explicit and implicit visual abilities, and suggest that the residual early visual cortex mediates form and orientation processing in the absence of awareness.

Conjugate limb coordination after experience with an interlimb yoke: evidence for motor learning in the rat fetus.

This study investigated the capacity of the E20 rat fetus to adaptively alter patterns of interlimb coordination in a prenatal model of motor learning. Fetal limb movement was manipulated with an interlimb yoke, consisting of a fine thread attached at the ankles, which created a physical linkage between two limbs. Exposure to the yoke resulted in a gradual increase in conjugate movements of the yoked limbs during a 30-min training period, which persisted after removal of the yoke. Training effects were evident when the yoke was applied to two hindlimbs, two forelimbs, or a homolateral forelimb-hindlimb pair. A savings in the rate of acquisition also was observed when fetuses experienced yoke training in a second session. These data argue that the rat fetus can respond to kinesthetic feedback resulting from variation in motor performance, which suggests that experience contributes to the development of coordinated motor behavior before birth.

Behavioral test systems in marmoset monkeys.

A number of neurobehavioral methods have been developed to test behavior in marmoset monkeys. These test systems are (1) the bungalow test, which quantifies spontaneous explorative behavior, (2) the hand-eye coordination test, which tests a learned task of coordinated motor behavior, and (3) the fear-potentiated startle response, which tests and quantifies pathological anxiety manifested by a response of fright. The test systems are extensively discussed, and the value of these test systems is exemplified by applying them to neurological disorders to register disease activity and drug efficacy.

Cortical neurons require Otx1 for the refinement of exuberant axonal projections to subcortical targets.

Information processing in the nervous system depends on the creation of specific synaptic connections between neurons and targets during development. The homeodomain transcription factor Otx1 is expressed in early-generated neurons of the developing cerebral cortex. Within layer 5, Otx1 is expressed by neurons with subcortical axonal projections to the midbrain and spinal cord. Otx1 is also expressed in the precursors of these neurons, but is localized to the cytoplasm. Nuclear translocation of Otx1 occurs when layer 5 neurons enter a period of axonal refinement and eliminate a subset of their long-distance projections. Otx1 mutant mice are defective in the refinement of these exuberant projections, suggesting that Otx1 is required for the development of normal axonal connectivity and the generation of coordinated motor behavior.

Systemic injections of alpha-1 adrenergic agonists produce antinociception in the formalin test

The role of α 1 receptors in antinociception was investigated in the formalin test, a well established test of tonic pain. The effect of systemic injections of selective α 1-adrenergic agonists (phenylephrine and methoxamine), a mixed α agonist selective for α 2 receptors (ST-91), and 2 adrenergic antagonists (prazosin and idazoxan) was measured in groups of Long-Evans rats. All agonists tested produced significant antinociception in this test. Dose-response curves for each agonist were statistically parallel and equally efficacious (100% antinociception). Prior injection of 0.15 mg/kg prazosin (an α 1 antagonist) completely antagonized the antinociception produced by either an ED 50 or a maximally effective dose of each agonist tested. Idazoxan (0.5 mg/kg), an α 2 antagonist, was without effect on the antinociception produced by phenylephrine or methoxamine. ST-91 produced significant antinociception in the presence of idazoxan although the response was different from that obtained with ST-91 alone. The observed antinociception in the formalin test was not due to drug-induced changes in peripheral inflammation as measured using plethysmometry. Moreover, none of the drugs tested produced significant changes in coordinated motor behavior (accelerated rotarod test) at doses that produced significant analgesia (ED 50). We conclude that α 1 receptors contribute significantly to adrenergic analgesia in the formalin test by an undefined action on sensory processing mechanisms.

An Inexpensive Rotarod for Behavioral Studies

Yearly there are increased objections to using physiological and surgical procedures on vertebrate animals, yet student interest remains high for these types of animals. The instrument described in this article allows students to perform a carefully planned, humane project and still get results which can be quantified. This approach utilizes the measurement of the effects of reversible physiological changes on the motor coordination of laboratory animals. The term is rather selfexplanatory, as it implies a rotating rod. The rotarod is used to measure coordinated motor activity. Laboratory mice, gerbils, rats, other rodents are placed on a rotating rod. In order to stay on the rod, the rodent must walk in a direction against the direction of rotation. Coordinated motor behavior, not fatigue, is measured by determining the length of time correct behavior is maintained. The main components of the apparatus (fig. 1) are 1) 7.5 cm diameter X 10 cm long dowels with centrally drilled holes; 2) a 90 cm threaded rod; 3) several plastic disks or old phonograph records; 4) a multispeed motor or motor with a rheostat speed control; and 5) a supporting frame. Using these components, this apparatus can easily and inexpensively be constructed by the instructor and/or students. (fig. 2). Several of the components can alter the time spent on the rod. The FIGURE 1. This rotarod, with locally purchased components, was constructed for under $25.00.