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[The characteristics of the adaptive behavior, neurological recovery and a morphometric analysis of the cerebral cortex in rats in the postresuscitation period].

Rats recovered after a 10-min circulation arrest, were examined in the early postresuscitation period (within 10-12 days after resuscitation) in an open field (OF) test and during elaboration and reproduction of passive avoidance conditioned reflex (PACR); morphometric analysis of sensorimotor brain cortex was performed on days 4, 7, 14, and 30 after resuscitation. It has been shown that directly after compensation of external neurological deficit which took place in the majority of animals within 3 days the process of adaptation to new situation (OF test) in resuscitated rats, unlike the intact ones, was associated with high motor activity and not with the elaboration of stable correlations between various behavioral acts. At the same time disorders in learning and memory have been observed in PACR test. Morphometric studies have revealed changes in neuroglial relations by day 14 and considerable dystrophic neuronal changes by month 1 after resuscitation. All these disturbances took place with the overall density of neuron population preserved.

Adaptation, Physiological↗

Behavioral effects of the alpha(2)-adrenoceptor antagonist, atipamezole, after focal cerebral ischemia in rats.

The present study characterized the behavioral effects of the selective alpha(2)-adrenoceptor antagonist, atipamezole, in a rat model of focal cerebral ischemia. Atipamezole (1 mg/kg, s.c.) or desipramine (5 mg/kg, i.p.), a noradrenaline reuptake blocker, was administered either as a single injection 2 days after ischemia induction or for 10 days thereafter (subacute administration). A subacute atipamezole treatment given 30 min before behavioral assessment improved performance in the limb-placing test (days 5, 7, 9, and 11) and in the foot-slip test (days 3 and 7), but not in the beam-walking test. There was no difference between experimental groups in behavioral performance following a single administration of atipamezole or following single or subacute administration of desipramine. The drug treatments did not attenuate the impairment of spatial cognitive performance of ischemic rats in the Morris water-maze test. These results suggest that repeated use-dependent release of noradrenaline by atipamezole facilitates the sensorimotor recovery following focal cerebral ischemia in rats.

Adrenergic Uptake Inhibitors↗

Behavioral effects of corpus callosum transection and environmental enrichment in adult rats.

A common assumption about the corpus callosum transection (CCX) is that it only affects behaviors heavily relying on interhemispheric communication. However, cerebral laterality is ubiquitous across motor and perceptual, cognitive and emotional domains, and the corpus callosum is important for its establishment. Several recent studies showed that the partial denervation of the sensorimotor isocortex through CCX derepressed neural growth processes that were sensitive to motor demand (experience-dependent neural plasticity). We investigated whether the facilitatory effects of CCX on cortical neural plasticity, shaped by differential housing, extended beyond the motor domain. Adult rats were housed in enriched (EE), standard (SE) or impoverished environments (IE) for 10 weeks, that is, 2 weeks before they underwent CCX or sham surgery, and, then, 8 weeks throughout the experiments. After they recovered from surgery, the behavioral performance of rats was tested using open-field, spontaneous alternation in the T-maze, paw preference, Morris water maze, and tone fear conditioning. The results indicated that the effects of CCX and housing on open-field behavior were independent, with CCX increasing the time spent in the center of the field at the beginning of the observation (i.e., emotionality), and EE and IE increasing rearing (emotionality) and reducing teeth-chattering (habituation), respectively. CCX reduced the frequency of spontaneous alternation, denoting spatial working memory deficits, while housing did not influence this performance. Neither CCX, nor housing significantly affected paw preference lateralization, although CCX was associated with a leftward bias in paw preference. In the Morris water maze, housing had effects on spatial acquisition, while CCX reduced activity, without interfering with spatial memory. CCX did not influence tone fear conditioning, but context fear conditioning seemed to benefit from EE. We conclude that CCX in adult rats has subtle, but specific behavioral effects pertaining to emotionality, spatial working memory, and, possibly, aversively motivated exploration, and these effects are either independent or only peripherally interact with the effects of housing.

Algorithms↗

Resolution of stroke deficits following contralateral grafts of conditionally immortal neuroepithelial stem cells.

BACKGROUND AND PURPOSE: Grafts of MHP36 cells have previously been shown to reduce dysfunction after global ischemia in rats. To test their efficacy after focal ischemia, MHP36 cells were grafted 2 to 3 weeks after transient intraluminal middle cerebral artery occlusion (tMCAO) in rats. METHODS: MHP36 cells were implanted into the hemisphere contralateral to the lesion, with 8 deposits of 3 microL of cell suspension (25 000 cells per microliter). Sham grafted rats received equivalent volumes of vehicle. Three groups, sham-operated controls (n=11), MCAO+sham grafts (n=10), and MCAO+MHP36 grafts (n=11), were compared in 3 behavioral tests. RESULTS: In the bilateral asymmetry test, MCAO+MHP36 grafted rats exhibited neglect before grafting but subsequently showed no significant dysfunction, whereas MCAO+sham grafted rats showed stable sensorimotor deficits over 18 weeks relative to controls. MCAO+sham grafted rats demonstrated spontaneous motor asymmetry and increased rotational bias after injection of dopamine agonists. MCAO+MHP36 and control groups exhibited no bias in either spontaneous or drug-induced rotation. In contrast to motor recovery, MCAO+MHP36 grafted rats showed no improvement relative to MCAO+sham grafted rats in spatial learning and memory in the water maze. MCAO produced large striatal and cortical cavitations in both occluded groups. Lesion volume was significantly reduced (P<0.05) in the MCAO+MHP36 grafted group. The majority of MHP36 cells were identified within the intact grafted hemisphere. However, MHP36 cells were also seen in the cortex, striatum, and corpus callosum of the lesioned hemisphere. CONCLUSIONS: MHP36 cells may improve functional outcome after MCAO by assisting spontaneous reorganization in both the damaged and intact hemispheres.

Amphetamine↗

Mutations that prevent associative learning in C. elegans.

The nematode Caenorhabditis elegans offers a promising system for the reductionist study of learning and memory. In this article, classical conditioning in C. elegans is demonstrated with a variety of associative learning assays. These assays allowed for the isolation and behavioral characterization of 2 mutant C. elegans lines impaired in associative learning. Both lines show no short-term or long-term associative conditioning; however, they appear relatively normal in tests of nonassociative learning and sensorimotor function. In combination with the well-described genetics and neuroanatomy of C. elegans, the isolation of mutants selectively, yet completely, blocked in associative learning provides the basis for an effective characterization of the cellular and molecular aspects of associative learning.

Animals↗

Startle and sensorimotor correlates of ventral thalamic dopamine and GABA in rodents.

Recent studies have implicated the thalamus as a possible site for neuroanatomical and neurochemical changes in schizophrenia. In the present study, we investigated thalamic neurochemical correlates of behaviors potentially linked to schizophrenia. Whole thalamic DOPAC levels were elevated in rats that had poor extinction of the acoustic startle response. The dopamine agonist apomorphine microinjected into the ventromedial thalamus (VmT) disrupted prepulse inhibition of startle. Catalepsy was induced by VmT microinjections of the GABA-A agonist muscimol. A previous study revealed attentional disturbances and suppression of frontal cortical metabolic activity after muscimol microinjections into the mediodorsal thalamic nucleus. Together with recent findings of neuron cell loss and elevated DA levels in the thalamus of schizophrenics, these data suggest the involvement of disturbances of thalamic neurotransmission in schizophrenia.

Analysis of Variance↗

A behavioral analysis of the spatial learning deficit induced by the NMDA receptor antagonist MK-801 (dizocilpine) in the rat.

This study analyzes whether the disruptive effects of the noncompetitive NMDA receptor antagonist MK-801 (0.01-0.1 mg/kg s.c.) on spatial learning can be dissociated from sensorimotor disturbances in the rat. Two different modifications of the Morris swim maze task with a hidden underwater platform were used: with or without local cue. Retention was tested either 24 h or 7 days after training as a probe trial (without platform). The present data indicate that MK-801 produces an impairment of spatial learning that cannot be dissociated from motor or sensory mechanisms. These findings support the view that NMDA receptors probably contribute to, but are not essential for, spatial learning in the water maze.

Animals↗

Focal traumatic brain injury causes widespread reductions in rat brain norepinephrine turnover from 6 to 24 h.

The effect of right sensorimotor traumatic brain injury (TBI) in male Sprague-Dawley rats on brain norepinephrine (NE) turnover was assessed by measuring the decline of endogenous NE levels following tyrosine hydroxylase inhibition produced with alpha-methyl-p-tyrosine. Right sensorimotor cortex contusions were produced by a pneumatically driven piston which depressed the dural surface by 2 mm at 3.2 m/s. TBI rats were compared to uninjured, anesthetized controls at 6 h and 24 h after surgery. While NE turnover was not affected at the lesion site at 6 h after TBI, it was either abolished or decreased by 33-75% bilaterally in the hypothalamus and in the cerebral cortex surrounding and rostral to the lesion site. In the cortex caudal to the lesion site, NE turnover was completely abolished. NE turnover in cerebral cortex opposite the lesion site and in the contralateral cerebellum was decreased by 51 and 43%, respectively, at 6 h. At 24 h, NE turnover was either abolished or decreased bilaterally by 45-92% in all cortical areas, in the hypothalamus, cerebellum, locus coeruleus and medulla. Thus, right sensorimotor cortex contusion causes a marked, early and widespread depression of brain NE turnover. Since amphetamine increases NE turnover, this may explain the dramatic improvement in behavioral deficits which occurs following amphetamine administration at 24 h after such lesions.

Animals↗

Decreased prepulse inhibition during nicotine withdrawal in DBA/2J mice is reversed by nicotine self-administration.

We characterized spontaneous and mecamylamine-precipitated nicotine withdrawal using intravenous nicotine self-administration, the acoustic startle response, prepulse inhibition and somatic signs of withdrawal in DBA/2J mice. Nicotine dependence was induced by continuous nicotine infusion through osmotic minipumps. Nicotine self-administration was studied before and after the induction of dependence. The initial test revealed significant nicotine self-administration at the 0.048 microg/infusion dose. During the second self-administration test, saline-treated mice exhibited increased aversiveness of response-contingent infusions of high nicotine doses; these changes were not seen in the nicotine-treated animals reflecting tolerance to nicotine's effects. Neither mecamylamine administration nor spontaneous withdrawal affected the expression of somatic signs, except that increases in jumping were observed during spontaneous withdrawal. Finally, nicotine withdrawal increased general activity in the startle chambers when no stimuli were presented, possibly reflecting increased body tremor and/or agitation, and decreased prepulse inhibition reflecting a sensorimotor gating deficit; the last two effects were reversed by nicotine self-administration. Thus, nicotine withdrawal results in modest, but yet detectable, changes in the behavior of mice.

Animals↗

A prospective study of motor recovery following multiple subpial transections.

A prospective study of motor recovery was undertaken in a patient scheduled to undergo multiple subpial transections (MST) of right sensorimotor cortex. Pre-transection, functional MRI (fMRI) and cortical stimulation mapping confirmed left hand motor control within right primary motor cortex. Immediately post-transection, behavioral testing demonstrated preserved strength bilaterally but decreased dexterity in the left hand. Seven weeks post-transection, dexterity returned to normal and left hand finger tapping corresponded with multiple bilateral foci of fMRI activation. At 16 weeks, fMRI activation returned to pre-transection levels. These data indicate that cortical injury due to MST resulted in the temporary recruitment of distant cortical sites which presumably subserved normal motor function during recovery.

Adult↗

Asymmetric and asynchronous infantile spasms.

Infantile spasms most commonly show symmetric behavioral and electroencephalogram (EEG) manifestations. Asymmetric and asynchronous behavioral spasms occur occasionally, but their relationship to ictal EEG and to other localizing studies has not received much attention. We reviewed 75 consecutive video-EEG recordings, done at UCLA from 1982 to 1992, that contained infantile spasms; 8,680 spasms were scored for behavioral and EEG asymmetry and asynchrony. Of the recorded spasms, 25% were asymmetric and 7% were asynchronous. Most asymmetric of asynchronous spasms were associated with an ictal EEG discharge that was contralateral to the behaviorally more involved side. In 12 of the 60 patients (20%), more than half of the recorded spasms were asymmetric of asynchronous. Baseline EEG, magnetic resonance imaging, positron emission tomography, and neurological examination revealed structural and functional brain abnormalities that involved the contralateral central region significantly more often in the children with > 50% spasm asymmetry or asynchrony than in the other children. Partial seizures with lateralized motor behavior also occurred frequently in these children. The findings suggest that asymmetric and asynchronous spasms are generated by a cortical epileptogenic region that involves the primary sensorimotor area. The combination of asymmetric and asynchronous infantile spasms, partial motor seizures involving the same side of the body, and pathology in the contralateral central region may represent a unique subset of symptomatic localization-related infantile epilepsy.

Cerebral Cortex↗

Internalizing agency of self-action: perception of one's own hand movements depends on an adaptable prediction about the sensory action outcome.

Extensive work on learning in reaching and pointing tasks has demonstrated high degrees of plasticity in our ability to optimize goal-directed motor behavior. However, studies focusing on the perceptual awareness of our own actions during motor adaptation are still rare. Here we present the first simultaneous investigation of sensorimotor adaptation on both levels, i.e., action and action perception. We hypothesized that self-action perception relies on internal predictions about the sensory action outcome that are updated in a way similar to that of motor control. Twenty human subjects performed out-and-back pointing movements that were fed back visually. Feedback was initially presented in spatiotemporal correspondence with respect to the actual finger position, but later rotated by a constant angle. When distorted feedback was applied repetitively, subjects' perceived pointing direction shifted in the direction of the trajectory rotation. A comparable perceptual reinterpretation was observed in control trials without visual feedback, indicating that subjects learned to predict the new visual outcome of their actions based on nonvisual, internal information. The perception of the world, however, remained unchanged. The changes in perception of one's own movements were accompanied by adaptive changes in motor performance of the same amount, i.e., a secondary motor compensation opposite to the direction of the imposed visual rotation. Our results show that the perception of one's own actions depends on adaptable internal predictions about the sensory action outcome, allowing us to attribute new sensory consequences of our actions to our own agency. Furthermore, they indicate that the updated sensory prediction can be used to optimize motor control.

Adult↗

Dissociation of morphological and physiological changes associated with long-term memory in aplysia.

Neurite outgrowth is a process commonly thought to contribute to long-term learning by formation of new synaptic contacts. The behavioral effects of long-term sensitization training in Aplysia were restricted to the trained side of the animal as were changes in strength of the sensorimotor synapse. In contrast, training produced varicosity formation on both sides of the animal. Appositions with follower neurons, however, were enhanced only on the trained side. The dissociation of structural and functional correlates suggests that key regulatory steps are downstream from outgrowth, possibly in the targeting of new processes and activation of new synapses.

Animals↗

Changing brain networks for visuomotor control with increased movement automaticity.

Learning a motor skill is associated with changes in patterns of brain activation with movement. Here we have further characterized these dynamics during fast (short-term) learning of a visuomotor skill using functional magnetic resonance imaging. Subjects (n = 15) were studied as they learned to visually track a moving target by varying the isometric force applied to a pressure plate held in the right hand. Learning was confirmed by demonstration of improved performance and automaticity (the relative lack of need for conscious attention during task execution). We identified two distinct, time-dependent patterns of functional changes in the brain associated with these behavioral changes. An initial, more attentionally demanding stage of learning was associated with the greatest relative activity in widely distributed, predominantly cortical regions including prefrontal, bilateral sensorimotor, and parietal cortices. The caudate nucleus and ipsilateral cerebellar hemisphere also showed significant activity. Over time, as performance improved, activity in these regions progressively decreased. There was an increase in activity in subcortical motor regions including that of the cerebellar dentate and the thalamus and putamen. Short-term motor-skill learning thus is associated with a progressive reduction of widely distributed activations in cortical regions responsible for executive functions, processing somatosensory feedback and motor planning. The results suggest that early performance gains rely strongly on prefrontal-caudate interactions with later increased activity in a subcortical circuit involving the cerebellum and basal ganglia as the task becomes more automatic. Characterization of these changes provides a potential tool for functional "dissection" of pathologies of movement and motor learning.

Adult↗

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↗

The basal ganglia and motor control.

This paper briefly reviews the functional anatomy of the basal ganglia and their relationships with the thalamocortical system. The basal ganglia, including the striatum, pallidum, subthalamic nucleus, and substantia nigra, are involved in a number of parallel, functionally segregated cortical-subcortical circuits. These circuits support a wide range of sensorimotor, cognitive and emotional-motivational brain functions. A main role of the basal ganglia is the learning and selection of the most appropriate motor or behavioral programs. The internal functional organization of the basal ganglia is very well suited for such selection mechanisms, both in development and in adulthood. The question of whether clumsiness may be, at least in part, attributed to dysfunction of the basal ganglia is discussed in the context of the differential, complementary, or interactive roles of the basal ganglia and the cerebellum in the development of motor control.

Animals↗

[Complicated oculomotor disorders evaluated by the medical expert].

The association of sensory and motor defects may lead the medical expert to a false estimation of a patient's impairment, especially (1) if he simply adds to the sensory impairment of one eye the motor impairment of the other, without thinking of the eyes as a paired organ; (2) if he underestimates a cumulation of sensory and motor defects in the case of partial adaptation, and (3) if he judges from dyskinetic behavioral characteristics that the patient is blind. Several clinical cases illustrating these problems and allowing the following recommendations are described: (1) Prior to simply summing up the single impairments one should examine if an overlap exists. (2) In the case of cumulative disturbances with incomplete adaptation the estimated impairment should be higher. (3) To estimate an individual sensorimotor impariment that is not covered by the common recommendations, one should refer to analogous impairments, e.g. hemianopias or zones of diplopia. One should further have in mind that a patient's impairment not only depends on the objective defects, but on his personality as well. (4) Oculomotor behavioral characteristics of multiply handicapped children or of demented patients must be taken into account in order to decide whether the patient is blind or not.

Adolescent↗

Neural mediation of nursing and related maternal behaviors.

Nursing is the behavioral concomitant of lactation and the most generalizable maternal behavior across mammals. In lactating rats nursing often occurs in the kyphotic (upright crouched) posture; like the neuroendocrine determinants of milk synthesis and release, kyphosis requires suckling by the young. The dam's active pronurturant behaviors, such as retrieval and licking of pups, requires perioral somatosensory stimulation, which is often a precursor of kyphosis as well, and is inhibited by suckling. The sequential nature of maternal behaviors and the dissociations in their somatosensory regulation are critical to understanding their neural mediation, as exemplified by our recent work in lactating rats. We found that the caudal lateral and ventrolateral midbrain periaqueductal gray (cPAGl,vl) is a sensorimotor integration site for the kyphotic nursing posture. Destruction of the cPAGl,vl, or increased activity of the inhibitory neurotransmitter GABA within it, severely reduced kyphosis, increased nursing in more atypical postures, and had little or no effect on pronurturance. Various forebrain sites are known to mediate retrieval and licking of pups. Inhibition of dopaminergic activity in the nucleus accumbens of dams via microinfusions of a mixed D1/D2 dopamine receptor antagonist, cis-flupenthixol (FLU), dose-dependently reduced these active behaviors, while increasing nursing duration. Retrieval was inhibited, however, only by infusions of FLU that included the nucleus accumbens shell, which is reciprocally connected with other sites implicated in retrieval of pups. Thus, maternal behavior is not a unitary process but rather a complex category consisting of sequential behavioral components that have their own sensory and neural determinants.

Animals↗