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PubMed1986

Inhibition of ornithine decarboxylase alters neurological responsiveness to a tremorigen.

Difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC; 200-800 mg/kg, s.c.), to rats has no detectable behavioral effects using a battery of tests to assess sensorimotor function. In contrast, the induction of tremor by chlordecone, a neurotoxic agent that affects neuronal ionic processes, is significantly attenuated by pretreatment with DFMO. The effects of DFMO on chlordecone-induced tremor were reversed by pretreatment with putrescine. DFMO had no effects on p,p'-DDT, a tremorigen having a mechanism of action different from chlordecone. These findings imply that polyamines may play a role in select neuronal processes.

Animals↗

PubMed2003

Involvement of the nucleus accumbens in the formation of spatial selection reactions in rats in a radial maze.

Studies on rats demonstrated that lesioning of the medial shell of the nucleus accumbens led to impairment of the ability of experimental rats to perform error-free identification of the arm containing the largest amount of reinforcement in a radial maze. The behavioral deficit was not associated with impaired motivation or sensorimotor learning ability, as there was no such deficit in operated rats during sequential presentation of local discriminant stimuli identifying the location of the forthcoming reinforcement. These data suggest that the medial shell of the nucleus accumbens, which receives convergent projections from the ventral hippocampus, amygdala, and ventral tegmental area, plays an important role in organizing the spatial orientation of the animal in the direction of the preferred reinforcement in conditions of a sensory information deficit.

Animals↗

PubMed1990

A D2 dopamine receptor agonist disrupts sensorimotor gating in rats. Implications for dopaminergic abnormalities in schizophrenia.

Prepulse inhibition of acoustic startle is deficient in schizophrenic patients and in animals injected with either direct or indirect dopamine (DA) agonists. The present experiments confirmed the hypothesis that the dopaminergic blockade of prepulse inhibition is attributable to the activation of D2 DA receptors. After systemic administrations of the D1 agonist SK&F 38393, the D2 agonist quinpirole, or a combination of the two, rats were tested for prepulse inhibition of the startle response by presenting acoustic stimuli or acoustic stimuli preceded by weak prepulses that inhibit startle. Although the D1 agonist SK&F 38393 had no effect on prepulse inhibition [0.3 to 30.0 mg/kg (1.03 to 102.82 mumols/kg)], the D agonist, quinpirole, blocked prepulse inhibition at doses of 0.3 mg/kg (1.17 mumols/kg) and 0.9 mg/kg (3.51 mumols/kg). Lower doses of quinpirole, 0.03 mg/kg (0.12 mumols/kg) and 0.1 mg/kg (0.39 mumols/kg), were ineffective. When an ineffective dose of quinpirole (0.1 mg/kg) was coadministered with 10.0 mg/kg SKF 38393, prepulse inhibition was reduced relative to saline controls. This reduction of prepulse inhibition is consistent with the synergistic effect of D1 and D2 DA receptor stimulation noted in studies of dopaminergic influences on stereotyped behavior in rats. These findings confirm that a disruption of sensorimotor gating results from D2 dopaminergic stimulation in the rat and extend the applicability of this animal model for the similar behavioral deficits exhibited by schizophrenic patients.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1997

Regulation of prepulse inhibition by ventral pallidal projections.

The acoustic startle reflex is inhibited by the presentation of a weak auditory prestimulus 30-500 ma prior to the starting stimulus. Previous studies have demonstrated that prepulse inhibition (PPI) of acoustic startle is regulated by GABAergic activity in the ventral pallidum. Ventral pallidal efferents include major projections to the pedunculopontine tegmental nucleus (PPTg), subthalamic nucleus (STN), and mediodorsal thalamus (MD). We used lesion and intracerebral infusion techniques to determine the relevance of these projections to the ventral pallidal regulation of PPI. Consistent with previous results, PPTg lesions significantly reduced PPI in all startle sessions, while MD lesions significantly reduced PPI only under certain experimental conditions. STN lesions failed to alter PPI, but they did significantly disrupt amphetamine-induced locomotion, verifying the behavioral effectiveness of these lesions. Infusion of the GABA-A agonist muscimol into either the PPTg or the MD significantly reduced PPI. Ventral pallidal projections to the PPTg and to the MD thus appear to regulate PPI, possibly via a GABAergic mechanism. Pallidal projections to the STN may regulate other behavioral processes such as locomotor activity, but they do not appear to regulate sensorimotor gating of the acoustic startle reflex.

Acoustic Stimulation↗

PubMed1991

The role of the inferior collicular cortex in the neonatal rat: sensorimotor modulation.

A tail pinch in rats up to 10 days of age produces a spectrum of motor behaviors characterized by forelimb paddling, hindlimb treading and occasional curling and rolling of the torso, a behavioral pattern similar to the seizure behaviors electrically-elicited from the inferior collicular cortex of 5- or 10-day-old rats. In 5-day-old rats, these tail pinch-induced paddling and treading behaviors coincided with afterdischarge-like EEG activity recorded from the seizure-sensitive site in the inferior collicular cortex. In contrast, no change in the EEG activity occurred in an adjacent seizure-insensitive site during these tail pinch-induced behaviors. Similar electrographic-behavioral synchrony was found in 10-day-old rats, but by 16 days of age, as in the adult rat, a tail pinch stimulus did not induce post-stimulus behavioral changes or afterdischarge-like EEG activity. Since auditory function does not develop until 12-14 days of age in the rat, we propose that the inferior collicular cortex modulates sensorimotor integration in the neonatal rat, prior to assumption of this function by the cerebral cortex.

Animals↗

PubMed1978

A behavioral analysis of complete unilateral section of the pyramidal tract at the medullary level in Macaca mulatta.

Ten Macaca mulatta monkeys were operantly conditioned to perform three motor paradigms designed to evaluate single and combination finger movements. Eight of these monkeys were retested after left medullary pyramidotomy; 2 monkeys underwent left medullary pyramidotomy prior to conditioning. All animals were tested for three years after operation. Monkeys with a completely sectioned medullary pyramid could, with time, perform difficult motor paradigms that required: (1) both individual and combination finger movements; (2) proximal upper extremity motor control; (3) thumb and index finger pincer grasp; and (4) the ability to preprogram and then execute a precision hand movement. The greater the extent of pyramidal tract destruction, the longer the time necessary for recovery of both discrete finger movement and pincer grasp, the greater the effort needed to attain recovery of hand function, and the weaker the affected musculature. The 2 animals in which pyramidotomy of at least 70% of the tract preceded efforts at operant conditioning learned and performed difficult motor paradigms. In all animals, neurological examination revealed that the most enduring and functionally most important deficit that interferes with hand function following pyramidotomy is loss of contactual hand orienting responses and failure of reflex sensorimotor adjustments.

Animals↗

PubMed2006

Restricted and repetitive behaviors in young children with autism spectrum disorders.

Restricted and repetitive behaviors (RRBs) on the Autism Diagnostic Interview- Revised (ADI-R: Lord, Rutter, & Le Couteur (1994) were examined in 165 children with Autism Spectrum Disorders (ASD), 49 children with non-spectrum developmental disorders (DD), and 65 children with typical development (TD) at approximately 2 years of age. A factor analysis found evidence for a repetitive sensorimotor (RSM) factor and an insistence on sameness (IS) factor. Behaviors that loaded on the RSM factor were prevalent in children with ASD and significantly more common and severe than in children with DD or TD. On average, children with ASD had more RSM behaviors. Behaviors that loaded on the IS factor were relatively uncommon and did not differ in prevalence or severity across groups.

Autistic Disorder↗

PubMedDate not supplied

Changes in power and coherence of brain activity in human sensorimotor cortex during performance of visuomotor tasks.

Electrocorticograms (ECoG) were recorded using subdural grid electrodes in forearm sensorimotor cortex of six human subjects. The subjects performed three visuomotor tasks, tracking a moving visual target with a joystick-controlled cursor; threading pieces of tubing; and pinching the fingers sequentially against the thumb. Control conditions were resting and active wrist extension. ECoGs were recorded at 14 sites in hand- and arm-sensorimotor area, functionally identified with electrical stimulation. For each behavior we computed spectral power of ECoG in each site and coherence in all pair-wise sites. In three out of six subjects, gamma-oscillations were observed when the subjects started the tasks. All subjects showed widespread power decrease in the range of 11-20 Hz and power increase in the 31-60 Hz ranges during performance of the visuomotor tasks. The changes in gamma-range power were more vigorous during the tracking and threading tasks compared with the wrist extension. Coherence analysis also showed similar task-related changes in coherence estimates. In contrast to the power changes, coherence estimates increased not only in gamma-range but also at lower frequencies during the manipulative visuomotor tasks. Paired sites with significant increases in coherence estimates were located within and between sensory and motor areas. These results support the hypothesis that coherent cortical activity may play a role in sensorimotor integration or attention.

Epilepsy↗

PubMed2004

Adaptive behavior of cortical neurons during a perturbed arm-reaching movement in a nonhuman primate.

This chapter provides evidence of spatial and temporal changes in the behavior of neurons within Areas 5 and 4 of the sensorimotor cortex of a nonhuman primate while it was executing a perturbed arm-reaching task. Chronically implanted electrode arrays were used to record simultaneously from 37 to 58 neurons. Also measured were the trajectory of arm movement, EMG activity in selected arm muscles and the perturbation force applied to the arm. The adaptation in Area 4 neurons' behavior usually involved a reduction in the latency from the onset of the perturbation to the peak-firing rate of the cell. In contrast, Area 5 neurons exhibited no such adaptive change in this latency. In each cortical area, the adaptation was not uniform across all neurons, and the spatial pattern of neuronal population behavior changed over the period of behavioral adaptation. We also found that the direction of arm movement and its configuration were important in determining which control strategy (predictive trajectory compensation or stiffness control) the animal used to overcome the externally applied perturbation for an improved performance of the reaching task.

Adaptation, Physiological↗

PubMed1989

Continued administration of GM1 ganglioside is required to maintain recovery from neuroleptic-induced sensorimotor deficits in MPTP-treated mice.

Injection of a dose of haloperidol that has no obvious behavioral effects in normal mice, produces akinesia, catalepsy, and sensory neglect in MPTP-treated mice. Chronic GM1 ganglioside administration improves the behavioral impairments, partially restores striatal dopamine (DA) content and prevents DA D-2 receptor up-regulation. Discontinuation of GM1 ganglioside treatment results in a time-dependent decline of striatal DA content to pretreatment pathological levels, return of haloperidol-induced sensorimotor deficits and a rise of DA D-2 receptor density in the striatum. Apparently, continuous administration of GM1 ganglioside is necessary to maintain the biochemical and behavioral recovery in the MPTP-treated mouse. These observations may provide useful cues for understanding the mechanism of action of GM1 ganglioside.

Animals↗

PubMed2003

Functional connectivity between the superficial and deeper layers of the superior colliculus: an anatomical substrate for sensorimotor integration.

The superior colliculus (SC) transforms both visual and nonvisual sensory signals into motor commands that control orienting behavior. Although the afferent and efferent connections of this midbrain nucleus have been well characterized, little is know about the intrinsic circuitry involved in sensorimotor integration. Transmission of visual signals from the superficial (sSC) to the deeper layers (dSC) of the SC has been implicated in both the triggering of orienting movements and the activity-dependent processes that align maps of different sensory modalities during development. However, evidence for the synaptic connectivity appropriate for these functions is lacking. In this study, we used a variety of anatomical and physiological methods to examine the functional organization of the sSC-dSC pathway in juvenile and adult ferrets. Axonal tracing in adult ferrets showed that, as in other species, sSC neurons project topographically to the dSC, providing a route for the transmission of visual signals to the multisensory output layers of the SC. We found that sSC axons terminate on dSC neurons that stain prominently for the NR1 subunit of the NMDA receptor, a subpopulation of which were identified as tectoreticulospinal projection neurons. We also show that the sSC-dSC pathway is topographically organized and mediated by monosynaptic excitatory synapses even before eye opening in young ferrets, suggesting that visual signals routed via the sSC may influence the activity of dSC neurons before the emergence of their multisensory response properties. These findings indicate that superficial- to deep-layer projections provide spatially ordered visual signals, both during development and into adulthood, directly to SC neurons that are involved in coordinating sensory inputs with motor outputs.

Age Factors↗

PubMed2006

Modulation of excitability as an early change leading to structural adaptation in the motor cortex.

The excitability of the motor cortex is a function of single cell excitability, synaptic strength, and the balance between excitatory cells and inhibitory cells. Sustained periods of sensory stimulation enhance the excitability in the motor cortex. This adaptation, which represents an early change in cortical network function effective in motor learning and recovery from a motor deficit, is followed by longer-lasting changes, such as modifications in cortical somatotopy, and by structural plasticity. Interventions aiming at increasing excitability also positively affect learning processes. Recent studies highlight that the cerebellum, especially the interpositus nucleus, plays a key function in the adaptation of the motor cortex to repeated trains of peripheral stimulation. Interpositus neurons, which receive inputs from the sensorimotor cortex and the spinal cord, are involved in somesthetic reflex behaviors and assist the cerebral cortex in transforming sensory signals to motor-oriented commands by acting via the cerebello-thalamo-cortical projections. Moreover, climbing fibers originating in the inferior olivary complex and innervating the nucleus interpositus mediate highly integrated sensorimotor information derived from spinal modules. The intermediate cerebellum allows the motor cortex to tune the gain of polysynaptic responses originating from the spinal cord after repetitive trains of peripheral stimulation, allowing an online calibration of cutaneo-muscular responses.

Adaptation, Physiological↗

PubMed2005

Modulation of motor cortex excitability by sustained peripheral stimulation: the interaction between the motor cortex and the cerebellum.

The excitability of cortical neurons in the motor cortex is determined by their membrane potential and by the level of intracortical inhibition. The excitability of the motor cortex as a whole is a function of single cell excitability, synaptic strength, and the balance between excitatory cells and inhibitory cells. It is now established that a sustained period of somatosensory stimulation increases the excitability of motor cortex areas controlling muscles in those body parts that received the stimulation prior to excitability testing. So far, it has been supposed that the sensorimotor cortex was the anatomical substrate of these excitability changes, which could represent an early change in cortical network function before structural plasticity occurs. Recent experimental studies highlight that the cerebellum, especially the interpositus nucleus, plays a key role in the adaptation of the motor cortex to repeated trains of stimulation. Interpositus neurons, which receive inputs from both sensorimotor cortex and the spinal cord, are involved in somesthetic reflex behaviors and assist the cerebral cortex in transforming sensory signals to motor-oriented commands by acting via the cerebello-thalamo-cortical projections. Moreover, climbing fibers originating in the inferior olivary complex and innervating the nucleus interpositus mediate highly integrated sensorimotor information derived from spinal modules. It appears that the interpositus nucleus is a main subcortical modulator of the excitability changes occurring in the motor cortex, which may be a substrate of early plasticity effective in motor learning and recovery from lesion.

Afferent Pathways↗

PubMedDate not supplied

Individual differences in aging: behavioral and neurobiological correlates.

The goal of this experiment was to determine the correlations among different behavioral and neurobiological measures in aged rats. Aged Sprague-Dawley rats were given a battery of cognitive and sensorimotor tests, followed by electrophysiological assessment of sleep and biochemical measurements of various neurotransmitter systems. The behavioral tests included the following: Activity level in an open field; short-term and long-term memory of a spatial environment as assessed by habituation: spatial navigation, discrimination reversal, and cue learning in the Morris water pool; spatial memory in a T-maze motivated by escape from water; spatial memory and reversal on the Barnes circular platform task; passive avoidance; motor skills. Sleep was assessed by electrographic cortical records. The following neurotransmitter markers were examined: Choline acetyltransferase; the density of nicotinic, benzodiazepine and glutamine receptors in the cortex and caudate nucleus; endogenous levels of norepinephrine, dopamine, and serotonin in the cortex and hippocampus. The duration of bouts of paradoxical sleep was strongly correlated with several cognitive measures and selected serotonergic markers. This finding suggests that changes in sleep patterns and brain biochemistry contribute directly to deficits in learning and memory, or that the same neurobiological defect contributes to age-related impairments in sleep and in learning and memory.

Age Factors↗

PubMed1997

Interaction of cognitive and sensorimotor maps of visual space.

Studies of saccadic suppression and induced motion have suggested separate representations of visual space for perception and visually guided behavior. Because these methods required stimulus motion, subjects might have confounded motion and position. We separated cognitive and sensorimotor maps without motion of target, background, or eye, with an "induced Roelofs effects": a target inside an off-center frame appears biased opposite the direction of the frame. A frame displayed to the left of a subject's center line, for example, will make a target inside the frame appear farther to the right than its actual position. The effect always influences perception, but in half of our subjects it did not influence pointing. Cognitive and sensorimotor maps interacted when the motor response was delayed; all subjects now showed a Roelofs effect for pointing, suggesting that the motor system was being fed from the biased cognitive map. A second experiment showed similar results when subjects made an open-ended cognitive response instead of a five-alternative forced choice. Experiment 3 showed that the results were not due to shifts in subjects' perception of the felt straight-ahead position. In Experiment 4, subjects pointed to the target and judged its location on the same trail. Both measures showed a Roelofs effect, indicating that each trial was treated as a single event and that the cognitive representation was accessed to localize this event in both response modes.

Cognition↗

PubMed1999

[Relationship between tics and compulsion].

In children and adolescents motor/vocal tics and obsessive-compulsive behavior are known to be closely related. Thereby, a continuum of symptoms ranging from single tics to a mixed picture of tics/rituals/obsessive-compulsive traits to clinically relevant obsessions and compulsions could be described. As neurobiological substrates dysfunctions in corresponding cortico-striato-thalamocortical circuits (sensorimotor circuit in tic symptomatology, orbitofrontal circuit in obsessive-compulsive behavior) were postulated. For both disturbances behavioral therapy can be used to improve control mechanisms to counterregulate tics and obsessive-compulsive behavior, respectively, and psychopharmacological agents can be administered to compensate dysbalances in neurotransmitter systems. In case of a mixed symptomatologic picture it is necessary to include interventions for both pols of the symptom-continuum in the therapeutic programme to achieve extensive improvement as a basis for a further positive development of the patient.

Adolescent↗

PubMed2001

Role of tonically active neurons in primate caudate in reward-oriented saccadic eye movement.

Recent studies have suggested that the basal ganglia are essential for reward-oriented behavior. A popular proposal is that the interaction between sensorimotor and reward-related signals occurs in the striatal projection neurons. However, the role of interneurons remains unclear. Using the one-direction-rewarded version of the memory-guided saccade task (1DR), we examined the activity of tonically active neurons (TANs), presumed cholinergic interneurons, in the caudate. Many TANs (73/155, 47.1%) responded, usually with a pause, to a visual cue that indicated both the saccade goal and the presence or absence of reward. For most TANs (44/73, 60.3%), the response was spatially selective (contralateral dominant), but was not modulated by the reward significance. TANs are thus distinct from caudate projection neurons, which have responses to the cue that are both spatially selective and reward contingent, and from midbrain dopamine neurons, which have cue responses that are spatially nonselective and reward contingent. TANs were nonetheless sensitive to the reward schedule: in the all-directions-rewarded version (ADR) compared with 1DR, the cue responses of TANs were smaller, less frequent, and less spatially selective. In 1DR, it would first be detected that reward is not given regularly, and this process would then promote discrimination of individual stimuli in relation to reward. We propose that TANs would contribute to the detection of the context that requires discrimination, whereas dopamine neurons would contribute to the stimulus discrimination. These features of TANs might be explained by their cytoarchitecture, namely, as large aspiny neurons.

Action Potentials↗

PubMed1999

Oxytocin modulates psychotomimetic-induced deficits in sensorimotor gating.

Oxytocin plays an important role in the regulation of normal cognitive functions and behaviors, which are disturbed in schizophrenia. Several studies suggest that oxytocinergic function is abnormal in schizophrenia patients. Thus, oxytocin may be involved in the pathophysiology associated with this disorder. This study investigated the regulatory effects of oxytocin on deficits in prepulse inhibition (PPI) associated with schizophrenia. Prepulse inhibition (PPI) is an operational measure of sensorimotor gating which can be measured across many species. PPI is the normal suppression of the startle reflex when the intense startling stimulus ("pulse") is immediately preceded by a weaker stimulus ("prepulse"). Subcutaneously administered oxytocin (0.04-1.0 mg/kg) dose-dependently restored PPI that had been reduced in rats by dizocilpine, a non-competitive NMDA antagonist, and by amphetamine, an indirect dopamine agonist. Oxytocin did not produce a significant effect on baseline PPI or PPI decreased by the direct dopamine agonist, apomorphine. The underlying startle response amplitude was also not significantly altered by oxytocin. These results suggest that oxytocin may play an important role in the modulation of dopaminergic and glutamatergic regulation of PPI, and that it may act as a novel endogenous antipsychotic.

Amphetamine↗