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PubMed2005

Generation and characterization of Rgs4 mutant mice.

RGS proteins are negative regulators of signaling through heterotrimeric G protein-coupled receptors and, as such, are in a position to regulate a plethora of biological phenomena. However, those have just begun to be explored in vivo. Here, we describe a mouse line deficient for Rgs4, a gene normally expressed early on in discrete populations of differentiating neurons and later on at multiple sites of the central nervous system, the cortex in particular, where it is one of the most highly transcribed Rgs genes. Rgs4(lacZ/lacZ) mice had normal neural development and were viable and fertile. Behavioral testing on mutant adults revealed subtle sensorimotor deficits but, so far, supported neither the proposed status of Rgs4 as a schizophrenia susceptibility gene (by showing intact prepulse inhibition in the mutants) nor (unlike another member of the Rgs family, Rgs9) a role of Rgs4 in the acute or chronic response to opioids.

Animals↗
PubMed1991

Effects of infant versus adult pyramidal tract lesions on locomotor behavior in hamsters.

The role of the pyramidal tract in locomotion was studied in hamsters by analyzing their locomotor behavior after lesions of the medullary pyramidal tract. Animals with lesions either as adults or as infants were compared to determine whether early pyramidotomy results in greater functional recovery. Normal and pyramidotomized animals were filmed during locomotion on a runway consisting of either smooth or rough terrain to assess whether the uneven surface would accentuate locomotor deficits. Frame-by-frame analysis of the filmed behavior during all phases of the step cycle was carried out to determine positions of the joints of the forelimb and hindlimb during locomotion. Accuracy of limb placement on the rough terrain was determined by observations of consecutive step cycles. The results show that lesions of the pyramidal tract in both infant and adult hamsters affect locomotion first by causing a reduction in the yielding phase of the step cycle and second by producing inaccuracies of forelimb placement. Rough terrain accentuates deficits in forelimb placement during locomotion. Animals with lesions as infants and those with lesions as adults show surprisingly similar deficits in locomotion, with the exception that animals with lesions as infants show some behavioral compensation in hindlimb movement by developing a normal degree of yielding at the knee. In contrast, hamsters with lesions as either adults or infants never recover normal forelimb behavior in either yielding at the elbow or accuracy of forelimb placement. These results emphasize the sensorimotor role of the pyramidal tract, even in a relatively stereotyped behavior such as locomotion.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed2000

Transient focal cerebral ischemia induces sensorimotor deficits in mice.

Rodents have been extensively used for experimental stroke research with rat and gerbil the preferred species. With the advent of transgenesis and gene targeting the number of mutant mouse strains is rapidly increasing. Thus, mouse models of stroke will be of great importance in the analysis of genetic factors affecting stroke. Demonstrating long-term functional recovery is of paramount importance for the pharmacological evaluation of putative stroke therapies. In the present paper we induce mild focal cerebral ischemia by tandem occlusion of the right middle cerebral artery (MCA), via craniotomy, together with the common carotid artery for 45 min in C57BL/6 strain of mice. The effects of ischemia were evaluated acutely by MRI and long-term (> 3 weeks) sensorimotor functional deficits were analyzed using a number of behavioral paradigms including the rotorod, wire hang, horizontal surface approach, eye-closure reflex, and T-maze tests. Although the induced brain damage is mild we show that it leads to clearly detectable and significant sensorimotor defects associated with fine motor coordination, balance, and postural and sensory reflexes. We conclude that the applied behavioral tests will be useful in the analysis of stroke in mutant mice.

Animals↗
PubMed2004

Postnatal physiological development of rats after acute prenatal hypoxia.

The aim of the present work was to identify the characteristics of the physiological development of the brain and the formation of behavior in rats subjected to hypoxia on day 13.5 of embryogenesis. These animals showed delayed development and changes in nerve tissue structure in the sensorimotor cortex, along with disturbances to the processes forming normal movement responses during the first month after birth. These changes were partially compensated with age, though adult animals subjected to acute prenatal hypoxia were less able to learn new complex manipulatory movements. Alterations in nerve tissue structure and changes in the neuronal composition of the sensorimotor cortex correlated with the times of appearance of behavioral impairments at different stages of ontogenesis. Thus, changes in the conditions in which the body is formed during a defined period of embryogenesis lead to abnormalities in the process of ontogenetic development and the ability to learn new movements.

Animals↗
PubMed2004

Perinatal inflammatory cytokine challenge results in distinct neurobehavioral alterations in rats: implication in psychiatric disorders of developmental origin.

Maternal stress, viral infection, and obstetric complications, which trigger cytokine signaling, are hypothesized to be involved in schizophrenia and its related disorders. The etiologic contribution of individual cytokines to such psychiatric disorders, however, remains to be evaluated. To estimate the impact of peripheral cytokine challenge on neurobehavioral development, we examined effects of four proinflammatory cytokines on rat neonates and their later behavioral performance. Sublethal doses of interleukin-1 alpha, interleukin-2, interleukin-6, or interferon-gamma were subcutaneously administered to rat pups for 9 days. These animals displayed alterations in physical development, including lower weight gain and/or accelerated eyelid opening. In addition, behavioral abnormalities related to fear/anxiety levels and sensorimotor gating emerged at different developmental stages, depending on the cytokine species administered. During juvenile stages, neonatal interleukin-2 treatment increased exploratory locomotor activity, whereas other cytokine treatments did not. At the post-puberty stage, however, the interleukin-2-induced abnormal motor activity became undetectable, whereas interleukin-1 alpha-treated rats developed abnormalities in startle response, prepulse inhibition (PPI), and social interaction. Subchronic treatment of an anti-psychotic drug, clozapine, ameliorated the impairment of prepulse inhibition without altering startle responses. These animal experiments illustrate that, during early postnatal development, inflammatory cytokine challenge in the periphery can induce future psycho-behavioral and/or cognitive impairments with various latencies, although the pathologic mechanisms underlying these abnormalities remain to be determined.

Animals↗
PubMed2001

Differential sensorimotor processing of vestibulo-ocular signals during rotation and translation.

Rotational and translational vestibulo-ocular reflexes (RVOR and TrVOR) function to maintain stable binocular fixation during head movements. Despite similar functional roles, differences in behavioral, neuroanatomical, and sensory afferent properties suggest that the sensorimotor processing may be partially distinct for the RVOR and TrVOR. To investigate the currently poorly understood neural correlates for the TrVOR, the activities of eye movement-sensitive neurons in the rostral vestibular nuclei were examined during pure translation and rotation under both stable gaze and suppression conditions. Two main conclusions were made. First, the 0.5 Hz firing rates of cells that carry both sensory head movement and motor-like signals during rotation were more strongly related to the oculomotor output than to the vestibular sensory signal during translation. Second, neurons the firing rates of which increased for ipsilaterally versus contralaterally directed eye movements (eye-ipsi and eye-contra cells, respectively) exhibited distinct dynamic properties during TrVOR suppression. Eye-ipsi neurons demonstrated relatively flat dynamics that was similar to that of the majority of vestibular-only neurons. In contrast, eye-contra cells were characterized by low-pass filter dynamics relative to linear acceleration and lower sensitivities than eye-ipsi cells. In fact, the main secondary eye-contra neuron in the disynaptic RVOR pathways (position-vestibular-pause cell) that exhibits a robust modulation during RVOR suppression did not modulate during TrVOR suppression. To explain these results, a simple model is proposed that is consistent with the known neuroanatomy and postulates differential projections of sensory canal and otolith signals onto eye-contra and eye-ipsi cells, respectively, within a shared premotor circuitry that generates the VORs.

Action Potentials↗
PubMed1981

Sensorimotor functioning and prelinguistic communication of severely and profoundly retarded individuals.

The prelinguistic, nonverbal communicative behavior of 40 institutionalized severely and profoundly retarded children and adolescents functioning at various stages of Piaget's sensorimotor period was examined. Five scales of the Uzgiris and Hunt (1975) sensorimotor assessment were used to determine general level of sensorimotor functioning. A standard set of communication elicitation tasks was employed to examine the gestures used to communicate in both imperative and declarative contexts. More competent sensorimotor performance was associated with higher frequency of more sophisticated and symbolic forms of gestural communication, and subjects generally used more complex gestures to communicate in the imperative than in the declarative tasks. Applicability of the results to the design of future language-intervention programs and their implications for general theory concerning the relations between language and cognition and between normal and atypical development were discussed.

Adolescent↗
PubMed1985

Behavioral study after local injection of 6-hydroxydopamine into the nucleus accumbens in the rat.

Anatomically, the nucleus accumbens (n.Acc.) has been considered as an interface between limbic and striatal sensorimotor structures. In the light of this hypothesis we have investigated the behavioral effects of destruction of the dopaminergic innervation of the n.Acc. after local injection of 6-hydroxydopamine. The following behavioral deficits were observed: hypoexploration in a 4-hole box and 2-compartment field, failure to inhibit response strategies either with positive reinforcement in a straight alley test or negative reinforcement in a passive avoidance test. These disturbances comprise a syndrome of perseveration, reduced distraction by irrelevant information, decreased behavioral switching and flexibility, and a paradoxical locomotor disinhibition in an emotional context. Very similar behavioral changes are found following lesions of limbic structures. In addition, these lesioned animals exhibit an enhanced latency to initiate motor responses. This deficit of behavioral initiation is classically observed in motor striatal disease. It is suggested that the n.Acc. is a key structure for the integration of limbic and striatal sensorimotor functions.

Animals↗
PubMed1992

Attention, play, and social behavior in ADHD preschoolers.

We investigated attention, play and nonplay behavior in preschool children with attention deficit hyperactivity disorder (ADHD) and a matched control group of non-ADHD children. Forty 4- to 5-year-old children (20 ADHD and 20 matched control) participated. Across a 6-week-period, children's social and play interactions as well as nonplay behaviors were videotaped in the classroom. Videotape recordings were analyzed for the level of attention, cognitive play, and social participation. In addition, children's level of attention and cooperative behavior were observed during two group activities. Findings indicated that ADHD, relative to non-ADHD, children engaged in less overall play and greater functional or sensorimotor play. ADHD children also engaged in more transitional behavior, were less competent with peers, and were less attentive and cooperative during group activities.

Attention↗
PubMed1978

Placement from community-based mental retardation programs: how well do clients do?

Mentally retarded clients (N = 131) placed during a 2-year period from either an independent living or competitive employment training program were evaluated as to placement success. Thirteen percent returned to the training program. Successful independent living placement was related to intelligence and demonstrated skills in symbolic operations, personal maintenance, clothing care and use, socially appropriate behavior, and functional academics. Successful employment was related to sensorimotor, visual-auditory processing, language, and symbolic-operations skills. Major reasons for returning from a job to the competitive employment training program included inappropriate behavior or need for more training; returning from community living placement was related to money management, apartment cleanliness, social behavior, and meal preparation.

Activities of Daily Living↗
PubMed1985

Earlier is not always better: behavioral dysfunction and abnormal cerebral morphogenesis following neonatal cortical lesions in the rat.

Rats with lesions of the medial frontal, ventral frontal or posterior parietal cortex in adulthood were compared behaviorally and neuroanatomically in adulthood with rats with similar removals at 7 days of age. The neonatal lesions altered cortical morphogenesis, especially in the ventral frontal and parietal groups, in which there was a marked thinning of remaining cortex distal to the lesion site. Behavior was assessed on an extensive battery of sensorimotor and maze-learning tests. Although there was sparing of function on some tests, the overall result was very little sparing on sensorimotor tests and only partial sparing on tests of maze learning in the frontal groups. The parietal neonates showed sparing on only one sensorimotor task and, in addition, showed unexpected deficits on sensorimotor and maze-learning tasks that were not observed in the adult operates. The results suggest that there may be more localization of function in the infant cortex than is generally believed and that early cortical damage may produce different behavioral effects than similar damage in adulthood.

Age Factors↗
PubMed2002

Extradural compression of sensorimotor cortex: a useful model for studies on ischemic brain damage and neuroprotection.

Behavioral and morphological changes were examined for up to 9 days after moderate cerebral ischemia caused by slow compression of a specific brain area in the sensorimotor cortex of Sprague-Dawley rats. Functional deficits after the cerebral ischemia were assessed by daily beam-walking tests, whereas morphological changes were verified using Nissl staining on day 1, 2, 3, 5, and 9, respectively. Rats exposed to cerebral ischemia displayed impaired beam walking performance. Mild hypothermia prevented both the compression-produced functional deficits and the brain damage. Younger (5 weeks) animals showed less neurological deficits than older (9 weeks) animals. Histological examination revealed a pronounced increase in the number of injured pyramidal neurons from day 1 to day 3 in the primarily damaged brain region. Between day 3 and day 5, the number of injured cells remained constant, whereafter there was a slow decline of thionin-positive neurons as examined on day 9. The noncompetitive NMDA receptor antagonist, dizocilpine (MK-801; 3 mg/kg, i.p.), did not alter the neurological impairment on day 1, but improved thereafter the rate of functional recovery and reduced the number of damaged cells. The AMPA receptor antagonist, LY326325 (15 or 30 mg/kg; i.p.), dose-dependently diminished the neurological deficits on day 1, enhanced the rate of recovery, and reduced the number of injured neurons over time. Our data suggest that short-lasting extradural compression of a well-defined brain area in the sensorimotor cortex is a highly reproducible model with a high success rate for the study of functional and morphological consequences after cerebral ischemia as well as for the evaluation of the therapeutic potential of novel, neuroprotective pharmacological agents.

Animals↗
PubMed2003

The selective A2A receptor antagonist SCH 58261 reduces striatal transmitter outflow, turning behavior and ischemic brain damage induced by permanent focal ischemia in the rat.

Adenosine A(2A) receptor antagonists have been proved protective in different ischemia models. In this study we verified if the protective effect of the selective A(2A) antagonist, SCH 58261, could be attributed to the reduction of the excitatory amino acid outflow induced by cerebral focal ischemia. A vertical microdialysis probe was inserted into the striatum of male Wistar rats and, after 24 h, permanent right intraluminal middle cerebral artery occlusion (MCAo) was induced. Soon after waking, rats showed a definite contralateral turning behavior, which persisted up to 7 h after MCAo. During 4 h after MCAo, glutamate, aspartate, GABA, adenosine and taurine outflow increased. SCH 58261 (0.01 mg/kg, i.p.), administered 5 min after MCAo, suppressed turning behavior and significantly reduced the outflow of glutamate, aspartate, GABA and adenosine. At 24 h after MCAo, the rats showed severe sensorimotor deficit and damage in both the striatum and cortex. SCH 58261 significantly reduced cortical damage but did not protect against the sensorimotor deficit. The protective effect of SCH 58261 against turning behavior and increased outflow of excitatory amino acids in the first hours after MCAo suggests the potential utility of selective adenosine A(2A) antagonists when administered in the first hours after ischemia. Furthermore, this study, for the first time, proposes that turning behavior after permanent intraluminal MCAo, be used as a precocious index of neurological deficit and neuronal damage.

Animals↗
PubMed1993

Neurological and behavioral effects of a unilateral frontal cortical lesions in fetal kittens. I. Brain morphology, movement, posture, and sensorimotor tests.

Nine fetal kittens sustained removal of the left frontal cortex during the last third of gestation (E 43-55) and were compared to animals sustaining a similar lesion postnatally (P 8-14) as well as to littermate controls. Starting after 6 months of age the animals received a comprehensive battery of movement, posture and sensorimotor tests. The prenatal-lesioned cats performed worse in practically all 15 tests applied (significantly in 13 of them) compared to the neonatal-lesioned cats. Impairments included contralateral paresis of the limbs and face, defective limb placing reactions (with almost absence of the contact components) and a slight extensor hypertonus; tactile hypoesthesia in the contralateral face and hind paw; a bias not to use the contralateral forepaw in a food retrieval task, and an ipsilateral body turning bias. The neonatal-lesioned animals only showed minor defects in the contact components of the limb placing reactions and a tendency to a body turning bias. Morphologically, the brains of the prenatal-lesioned cats, but not of neonatal-lesioned or intact control cats, showed bilateral disruption of the cortical sulcal and gyral patterns, shrinkage of the ipsilateral hemisphere, and reduction in volume of the ipsilateral thalamus and cortex. We concluded, contrary to expectations, that the consequences of a prenatal brain lesion in the cat are worse than when a similar lesion is sustained neonatally.

Animals↗
PubMed2006

A special case of learning disorder in isolant rats as a model of disintegration.

The combination of two factors - isolation and ontogenesis (starting from 21 days) and subsequent training of rats to a cyclical habit - could in some animals (30%) lead to the formation of unusual behavioral strategies consisting of maintenance of the cyclical habit without reinforcement with food. This dissociation from the vital motivation is regarded as an analog of the disintegration phenomenon, a key step in psychoneurotic disorders. The most common type of disturbance in isolated animals was suppression of searching activity, with extreme learning difficulty, though a training process including a two-month break led to a significant increase in motor-searching activity in this situation. These behavioral abnormalities were accompanied by morphological changes in the sensorimotor cortex of the brain, with a relative thinning of layer 5 and selective decreases in the density of satellite glial cells and deviations from the normal correlational relationships between behavioral and neuroglial measures.

Animals↗
PubMed1984

AF64A, a cholinergic neurotoxin, selectively depletes acetylcholine in hippocampus and cortex, and produces long-term passive avoidance and radial-arm maze deficits in the rat.

The behavioral and biochemical effects of AF64A, a presynaptic cholinergic neurotoxin, were investigated. Bilateral administration of this compound into the lateral cerebral ventricles produced transient and dose-related effects on sensorimotor function and long-term impairments of cognitive behavior. Male Fischer-F344 rats dosed with either 15 or 30 nmol of AF64A reacted 29-62% faster than CSF-injected controls in a hot-plate test 14 (but not 1, 7, 21 or 28) days following dosing. The group administered 15 nmol of AF64A was also significantly more active (41%) than controls 28 days following dosing. The activity level of this group was comparable to that of controls at other times and hyperactivity was never observed in the 30 nmol group. Retention of a step-through passive avoidance task, assessed 35 days after dosing, was impaired in both the 15 and the 30 nmol groups. Their step-through latencies were significantly shorter than the control latencies, and they exhibited more partial entries during the 24-h retention test. Radial-arm maze performance, measured 60-80 days following treatment, was markedly impaired in the treated groups. Animals treated with AF64A made fewer correct responses in their first 8 choices, required more total selections to complete the task, and had an altered pattern of spatial responding in the maze. The neurochemical changes produced by AF64A, determined 120 days after dosing, were specific to the cholinergic system and consisted of decreases of ACh in both the hippocampus (15 and 30 nmol groups) and the frontal cortex (30 nmol group). The concentrations of catecholamines, indoleamines, their metabolites and choline in various brain regions were not affected by AF64A. Furthermore, histological analysis revealed that the doses of AF64A used in the present study did not damage the hippocampus, the fimbria-fornix, the septum or the caudate nucleus. These data support the contention that cholinergic processes in the hippocampus and/or frontal cortex play an important role in learning and memory processes. Furthermore, based upon the behavioral and biochemical data presented, it is suggested that AF64A could be a useful pharmacological tool for examining the neurobiological substrates of putative cholinergic disorders such as senile dementia of the Alzheimer's type.

Acetylcholine↗
PubMedDate not supplied

[Role of the frontal cortex in organizing emotional-behavioral reactions induced by hypothalamic stimulation and natural stimuli].

Study of the effects of a functional switching off the sensorimotor neocortex area in cats by means of cooling reveals its inhibitory influence on emotional-behavioral reactions to hypothalamic stimulation. Multiple (up to 12) switchings off of the frontal neocortex are attended with a gradual compensation of its inhibitory function by the activity of other brain structures. On the other hand inactivation of the sensorimotor cortex reduces the ability of natural provoking stimuli to lower the thresholds of goal-directed rage which develops when these stimuli are combined with an electrical stimulation of the hypothalamus. A conclusion has been made on the participation of the frontal neocortex in the systemic organization of estimation of biologically significant stimuli.

Anger↗
PubMed2002

Cognitive and neuropsychological outcomes: more than IQ scores.

Improved survival in preterm infants has broadened interest in cognitive and neuropsychological outcomes. The incidence of major disabilities (moderate/severe mental retardation, neurosensory disorders, epilepsy, cerebral palsy) has remained consistent, but high prevalence/low severity dysfunctions (learning disabilities, ADHD, borderline mental retardation, specific neuropsychological deficits, behavioral disorders) have increased. The follow-up literature contains methodologic problems that make generalizations regarding outcome difficult, and these are discussed. Although mean IQs of former VLBW infants generally are in the low average range and are 3-9 points below normal birth weight peers, these scores mask subtle deficits in: visual-motor and visual-perceptual abilities, complex language functions, academics (reading, mathematics, spelling and writing), and attentional skills. There is an increased incidence of non-verbal learning disabilities, need for special educational assistance, and behavioral disorders in children born prematurely. Males have more problems, and there is a trend for worsening outcome over time, due to emergence of more subtle deficits in response to increased performance demands. In addition to IQ and achievement testing in follow-up, there should be evaluation of executive functions and attention, language, sensorimotor functions, visuospatial processes, memory and learning, and behavioral adjustment.

Cognition Disorders↗