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PubMed1997

Developmental changes in manipulation in tufted capuchins (Cebus apella) from birth through 2 years and their relation to foraging and weaning.

This study examined the contributions of physical and sensorimotor development to manipulation in capuchins (Cebus apella) from birth to 2 years. Between months 1-6 and 7-12, manipulation increased significantly in frequency, in the proportion that was vigorous or required fine motor control, and in the proportion directed at portable objects. Fine motor control, moving objects in relation to the body, and stamina are largely in place by 12 months, after which little changed. All elements of the manipulative repertoire have appeared, and vigorous and dexterous activities have peaked before fully independent foraging. Emergence of permanent dentition and achievement of approximately half of adult body size accompany the attainment of fully independent foraging at 15 months. Thereafter, increasing strength and specific knowledge probably contribute more to changing foraging competence in young capuchins than do stamina and sensorimotor development.

Aging↗
PubMed2003

Closed-loop neuronal computations: focus on vibrissa somatosensation in rat.

Two classes of neuronal architectures dominate in the ongoing debate on the nature of computing by nervous systems. The first is a predominantly feedforward architecture, in which local interactions among neurons within each processing stage play a less influential role compared with the drive of the input to that stage. The second class is a recurrent network architecture, in which the local interactions among neighboring neurons dominate the dynamics of neuronal activity so that the input acts only to bias or seed the state of the network. The study of sensorimotor networks, however, serves to highlight a third class of architectures, which is neither feedforward nor locally recurrent and where computations depend on large-scale feedback loops. Findings that have emerged from our laboratories and those of our colleagues suggest that the vibrissa sensorimotor system is involved in such closed-loop computations. In particular, single unit responses from vibrissa sensory and motor areas show generic signatures of phase-sensitive detection and control at the level of thalamocortical and corticocortical loops. These loops are likely to be components within a greater closed-loop vibrissa sensorimotor system, which optimizes sensory processing.

Afferent Pathways↗
PubMed1995

Input-output properties of hand-related cells in the ventral cingulate cortex in the monkey.

1. Neurons with proprioceptive or cutaneous receptive fields associated with the hand were identified in the ventral bank of the cingulate sulcus in the monkey. Cells with proprioceptive fields outnumbered cells receiving cutaneous afferents by more than three to one. No cells were encountered that received convergent proprioceptive and cutaneous input. The high concentration of these neurons in the lateral depth of the cingulate sulcus establishes that a distinct hand representation exists within the rostral part of area 23c. 2. Hand-related neurons in area 23c exhibited strong activity modulations during grasping, lifting, and holding an object with the contralateral thumb and index finger. Force pulse perturbations applied to the object elicited excitatory responses at latencies of approximately 45 ms. The modulation of the cellular activity and the input-output properties of these cingulate neurons suggest that, like neurons of primary motor and sensory cortex, these cingulate neurons are also involved in the sensorimotor control of finger movements.

Afferent Pathways↗
PubMed1996

Conditioned whisking in the rat.

The rat's mystacial vibrissae are active during exploratory and discriminative behaviors, with individual vibrissae serving as elements in a receptive array scanned across object surfaces. To facilitate neurobehavioral analysis of this sensorimotor system, we have developed an experimental paradigm that confines vibrissa movements to a defined physical location, makes possible on-line monitoring of "whisking" activity, and brings such activity under associative control using operant conditioning procedures. Rats were secured, and movements of an identified bilaterally homologous pair of vibrissae (right and left gamma straddlers) were detected by laser-based photodetectors. Subjects were maintained on a water deprivation schedule, and whisker movements were monitored during adaptation to the test situation and after the clipping of other vibrissae on both sides of the snout. Rats were reinforced with water delivery for emitting vibrissa movements in the presence of a conditioned stimulus (tone) whose presentation was made contingent upon a prior period of nonwhisking. The rate and temporal distribution of vibrissa movements were brought under experimental control by means of interval and ratio reinforcement schedules. Although the procedures provide minimal information about the kinematics or topography of conditioned vibrissa movements, they permit the investigator to manipulate response parameters normally under the voluntary control of the animal in a preparation amenable to neurophysiological analysis.

Animals↗
PubMed1986

Recovery of function after neonatal or adult hemispherectomy in cats: I. Time course, movement, posture and sensorimotor tests.

Cats with removal of the left hemitelencephalon (hemispherectomy) as neonates (n = 12) or in adulthood (n = 14), were compared using a battery of 16 neurological and behavioral tests given when they were young adults (kittens) or at least 5 months after the lesion (adults). The neonatal-lesioned subjects grew normally and performed markedly and significantly better than adult-lesioned cats in 13 tests covering the wide range of movement, posture and sensory functions which were assessed. None of the animals recovered tactile placing of the right forelimb or a normal vision in the right visual field. However, the overall recovery was outstanding for all cats such that the neonatal-lesioned were hard to differentiate from intact controls in their spontaneous, daily activities. Because the lesions were similar in the two age-at-lesion groups, and since numerous functions were followed for prolonged, comparable postlesion time, we conclude that, after hemispherectomy in the cat, there definitely is greater functional recovery if the lesion is sustained early in life. We propose that the enhanced recovery of function in neonatal-lesioned cats is largely due to the extensive anatomical reorganization which we have demonstrated in ongoing studies, and which contrasts with a lesser remodeling in adult-lesioned cats.

Age Factors↗
PubMed1992

A behavioral study of bilateral middle cerebral artery hemorrhagic ischemia in rats.

The middle cerebral artery was severed bilaterally (bMCA) in adult rats, and controls experienced sham operations. Tactile sensorimotor and gross locomotor functions, measured by the tape test and a rod walking test, were initially impaired in the injured animals. However, these deficits had resolved within 9 and 30 days respectively. The animals were trained in a multiple T water maze task to find the location of a hidden escape platform at the rate of one trial per day for 30 days. Analyses of the number of errors committed and latency to find the escape platform revealed that the bMCA injured rats suffered deficient reference memory, but no decline in working memory. These data support further the use of the bMCA preparation as a model of stroke.

Animals↗
PubMed1999

Dopamine denervation of specific striatal subregions differentially affects preparation and execution of a delayed response task in the rat.

In the present study, the effects of unilateral or bilateral dopamine denervation of either the dorsal or ventral striatum on the preparation and execution of a delayed response task in the rat were investigated. Animals were instructed to hold a lever pressed down by the presentation of a visual and/or acoustic signal, and were required to hold the lever until a trigger stimulus occurred after an unpredictable delay ranging from 2 to 4 s. The trigger stimulus required animals to release the lever and to press a second lever for food reinforcement. The time between instruction and trigger signal represented the preparation phase preceding movement. The motor performance was evaluated by using reaction and movement times in addition to correct responses in each session. Dopaminergic denervation of either the dorsal or ventral striatum ipsilaterally to the side in which the second lever to be pressed was located did not significantly change reaction and movement times, although it reduced the percentage of correct trials. A significant increase of both reaction and movement times was recorded only after bilateral denervation of the ventral striatum. The analysis of incorrect responses indicated that dopaminergic innervation of the two striatal subregions had different functions in the correct execution of the behavioral paradigm. In the group of animals with dorsal lesions the most frequent incorrect response was represented by a lack of the conditioned response to the presentation of the instruction stimulus starting the trial. If the animals reacted properly to this signal, the performance thereafter was correct in the majority of trials. Conversely, animals with ventral lesions exhibited a large repertoire of incorrect responses throughout the paradigm, including premature release or delayed press of levers, and omission of the second lever press. Histological verification of brain coronal sections by tyrosine-hydroxylase immunoreactivity showed that the lesions were confined in either the dorsal or ventral striatum, sparing the lateral region. The data support the hypothesis that dopaminergic innervation enables the two striatal regions to differently participate in the preparation and execution of complex delayed sensorimotor tasks. Indeed, the dorsal striatum seems to be involved in the correct utilization of external sensory information for the initiation of conditioned behavior, whereas, the ventral striatum appears to be mainly concerned with the temporal expectation of impending stimuli that trigger reward-reinforced movements.

Acoustic Stimulation↗
PubMed1991

Sparing of function after neonatal frontal lesions correlates with increased cortical dendritic branching: a possible mechanism for the Kennard effect.

This study examined the possibility that the presence or absence of behavioral sparing following neonatal frontal lesions might be correlated with changes in the complexity of dendritic branching. Rats were given bilateral frontal lesions in either adulthood, the day of birth, or on day 10. Ninety days later the animals were trained in a spatial navigation task. The animals' brains were then processed for Golgi-Cox staining and the dendritic branching of the pyramidal cells in the parietal cortex was analyzed. Frontal cortical lesions in newborn rats produced a severe behavioral deficit in the water task whereas frontal removal at 10 days of age allowed sparing of function relative to adult operates (that is, the Kennard effect). Analysis of dendritic arbor in sensorimotor cortex revealed that the day-10 animals exhibited a dramatic proliferation of dendritic arbor relative to control rats. In contrast, the day-1 animals had slightly less dendritic branching than control animals. Rats with frontal lesions in adulthood showed a small, but significant, increase in dendritic branching. The correlation between behavioral sparing and the increase in dendritic arborization following neonatal lesions may be illustrative of a general mechanism underlying the Kennard effect.

Animals↗
PubMed2000

A functional neuroanatomy of tics in Tourette syndrome.

BACKGROUND: Tics are involuntary, brief, stereotyped motor and vocal behaviors often associated with irresistible urges. They are a defining symptom of the classic neuropsychiatric disorder, Tourette syndrome (TS), and constitute an example of disordered human volition. The neural correlates of tics are not well understood and have not been imaged selectively. METHODS: Event-related [(15)O]H(2)O positron emission tomography techniques combined with time-synchronized audio and videotaping were used to determine the duration of, frequency of, and radiotracer input during tics in each of 72 scans from 6 patients with TS. This permitted a voxel-by-voxel correlational analysis within Statistical Parametric Mapping of patterns of neural activity associated with the tics. RESULTS: Brain regions in which activity was significantly correlated with tic occurrence in the group included medial and lateral premotor cortices, anterior cingulate cortex, dorsolateral-rostral prefrontal cortex, inferior parietal cortex, putamen, and caudate, as well as primary motor cortex, the Broca's area, superior temporal gyrus, insula, and claustrum. In an individual patient with prominent coprolalia, such vocal tics were associated with activity in prerolandic and postrolandic language regions, insula, caudate, thalamus, and cerebellum, while activity in sensorimotor cortex was noted with motor tics. CONCLUSIONS: Aberrant activity in the interrelated sensorimotor, language, executive, and paralimbic circuits identified in this study may account for the initiation and execution of diverse motor and vocal behaviors that characterize tics in TS, as well as for the urges that often accompany them. Arch Gen Psychiatry. 2000;57:741-748

Adult↗
PubMed1988

Receptor characteristics and recovery of function following kainic acid lesions and fetal transplants of the striatum. I. Cholinergic systems.

The relationship between striatal muscarinic cholinergic receptor development and locomotor activity/T-maze alternation behavior in adult female rats with kainic acid lesions (kal) and fetal transplants of the striatum (str) was examined. Kal led to a number of deficits under conditions of spontaneous locomotion, including: (1) decreased stereotypical and increased horizontal movements during spontaneous overnight locomotion, (2) decreased spontaneous alternation on a T-maze, and (3) deficits on a sensorimotor neurological exam. Lesion-induced deficits following injection with cholinergic agonists (pilocarpine)/antagonists (scopolamine) included: (1) hypoactivity on vertical activity and stereotypical activity following scopolamine injection, and (2) increased stereotypical activity and decreased horizontal activity following pilocarpine injection. Transplants differentially affected the different types of behavioral deficits. Transplants reversed some of the deficits under conditions of spontaneous locomotion, including the hyperactivity noted during the night period, but only partially reversed the sensorimotor neurological exam and had no effect on spontaneous alternations in the T-maze. The transplants did not reverse the lesion-induced deficits following scopolamine injection, but partially reversed the lesion-induced changes in locomotion following pilocarpine injection. The striatal transplants had reduced numbers of M1 but increased numbers of M2 muscarinic cholinergic receptors. Cholinergic receptor density correlated with scores on the sensorimotor functioning and alternation tasks, but not with the locomotor measures. Conversely, the cross-sectional area of the str correlated strongly with the transplant-induced recovery in the lesion group. These results suggest that the development of cholinergic receptor systems within the transplants proceeds abnormally, and that the abnormal development of the transplant may impact on the transplant's ability to remediate lesion-induced deficits.

Animals↗
PubMed2002

Intrastriatal grafting of glomus cells ameliorates behavioral defects of Parkinsonian rats.

Parkinson's disease is associated with severe motor dysfunctions due to a progressive loss of dopaminergic neurons in substantia nigra. Transplantation of midbrain neurons from human fetuses to the striatum of patients provides effective treatment for the disease. This type of approach, however, could not be adopted widely due to insufficient supply of fetal materials and the controversial ethical and legal issues. The carotid body is a chemoreceptive organ containing chromaffin-like glomus cells that secrete dopamine (DA) as the neurotransmitter. Here, we report the generation of a clonal dopaminergic cell line of the carotid body using the H-2K(b)-tsA58 transgenic mouse. Cells from the carotid body were immortalized at the permissive temperatures and in the presence of gamma-interferon. The glomus cells were isolated by flow cytometry, and purified to homogeneity by a limited dilution procedure. Upon switching the culture to a nonpermissive condition, the immortal cells ceased to divide, became terminally differentiated and secreted high levels of DA. In rats rendered hemi-Parkinsonian by injection of 6-hydroxydopamine (6-OHDA) into the substantial nigra, intrastriatal grafting of the glomus cells resulted in significant recovery of motor asymmetries and sensorimotor dysfunction. The effects were apparent approximately 10 days after transplantation and remained throughout the 4 months of the study. The recovery of behavioral defects was correlated with the ability of cell grafts to release DA in the brain. As none of the existing treatments for Parkinson's disease is completely satisfactory, establishment of a clonal cell line that secretes DA opens a new avenue for the effective control of this neurological disorder.

Amphetamine↗
PubMed1985

The epileptic nature of rodent electrocortical polyspiking is still unproven.

Electrocortical polyspiking has been reported in guinea pigs, tottering mice, and several strains of laboratory rats. Some investigators have interpreted the polyspiking activity (PSA) to be epileptic in nature, specifically analogous to human petit mal spike-wave discharges; others have assumed PSA to be the rodent equivalent of human mu and feline sensorimotor rhythms. This article provides additional data on PSA in rats, consistent with previous reports that it is associated with behavioral immobility, occurs spontaneously, is bilaterally symmetrical, has a frequency of about 7 to 9/s, and is associated with vibrissa tremor. The PSA frequency varied in relation to the difference between fast and slow vibrissa tremor, as reported previously. A review of these data and the nine earlier publications on PSA reveals that the epileptic nature of PSA is still unproven, and there is strong support for the proposal that it is a normal EEG pattern.

Animals↗
PubMed2005

Interleukin-1alphabeta gene-deficient mice show reduced nociceptive sensitivity in models of inflammatory and neuropathic pain but not post-operative pain.

The pro-inflammatory cytokine interleukin-1 (IL-1) has been implicated in both inflammatory processes and nociceptive neurotransmission. To further investigate the role of IL-1 in different pain states, gene-disrupted mice lacking both IL-1alpha and IL-1beta genes (IL-1alphabeta (-/-)) were characterized in inflammatory, neuropathic, and post-operative pain models. IL-1alphabeta (-/-) mice showed normal sensorimotor function as measured by the rotorod assay compared to control mice (BALB/c). Acute and persistent formalin-induced nocifensive behaviors were reduced by 20% in IL-1alphabeta (-/-) mice as compared to control mice. IL-1alphabeta (-/-) mice also showed reduced inflammatory thermal and mechanical hyperalgesia compared to controls following the intraplantar administration of carrageenan or complete Freund's adjuvant (CFA). The duration of inflammatory hyperalgesia was shortened in IL-1alphabeta (-/-) mice versus controls in the CFA model. In contrast, deletion of IL-1alphabeta did not change the extent or the duration of post-operative pain developing after skin incision of the hind paw. Finally, time to onset, duration, and magnitude of mechanical allodynia were reduced in two models of neuropathic pain, spinal nerve L5-L6 ligation and chronic constriction injury of the sciatic nerve, in IL-1alphabeta (-/-) mice versus controls. These results demonstrate that IL-1alphabeta modulates both the generation and the maintenance of inflammatory and chronic neuropathic pain and that IL-1 may modulate nociceptive sensitivity to a greater extent in conditions of chronic as compared to acute pain.

Acute Disease↗
PubMed1997

Nonhippocampal muscarinic receptors are required for nonspatial working memory.

The effects of scopolamine on nonspatial working memory were examined in rats with hippocampal lesions and sham operations. Performance was examined using a continuous conditional discrimination task in an operant box. Choice accuracy measured nonspatial working memory. Response bias, delay interval responses, and response probability measured response preference, stimulus control, motivation, and sensorimotor ability. Scopolamine (0.05, 0.075, 0.1, and 0.15 mg/kg) or methylscopolamine (0.1 mg/kg) was injected (I.P.) 15 min prior to behavioral testing. In both control and hippocampal lesioned groups, choice accuracy declined as the delay interval increased. Scopolamine, but not methylscopolamine, produced a dose-dependent impairment of choice accuracy (interaction of Dose x Delay) in both groups. The scopolamine-induced impairment was not different between the control and hippocampally lesioned rats. Response bias, delay interval responses, and response probability were not affected by scopolamine except at the highest dose, which increased delay interval responses. The results suggest that central muscarinic receptors outside the hippocampus are important for working memory of nonspatial stimuli.

Animals↗
PubMed1979

Acute homeostatic imbalances reinstate sensorimotor dysfunctions in rats with lateral hypothalamic lesions.

It has previously been demonstrated that rats recovered from aphagia and adipsia after large bilateral electrolytic lesions of the lateral hypothalamic area do not show the normal feeding response to 2-deoxyglucose or drinking response to polyethylene glyol. The present work reveals that such homeostatic imbalances reinstate the profound sensorimotor impairments that are seen in the immediate postoperative period but abate in parallel with the gradual recovery of ingestive behaviors. Administration of alpha-methyltyrosine or spiroperidol produced sensory and motor dysfunctions in rats with lateral hypothalamic lesions that were similar to those observed after 2-deoxyglucose. These results suggest that the residual feeding and drinking deficits of rats with lateral hypothalamic lesions after apparent recovery of function do not reflect specific loss of putative gluco- and volume-regulatory contributions to ingestive behavior. Instead, they may indicate continued impairments in nonspecific activational components of motivation that normally are mediated, in part, by central dopaminergic neurons.

Animals↗
PubMed1991

Cortical microstimulation thresholds adjacent to sensorimotor cortex injury.

The initial severe contralateral impairment of motor function after unilateral damage to a portion of sensorimotor (SM) cortex lessens within a few weeks after injury. In this study, two hypotheses proposed to explain recovery of behavioral function after cortical injury were tested: (1) Intact cortex adjacent to the injury reorganizes to take over the function of the destroyed area. (2) Intact SM cortex adjacent or connected to the injured area undergoes a transient shock (diaschisis), and as this dissipates, some behavioral recovery occurs. Using microstimulation of the cortex of the adult rat, movements evoked from areas near cortical injuries were studied at various times after undercut laceration, contusion, or suction ablation of an area of SM cortex. Stimulation areas were compared to those obtained from uninjured control animals and to the contralateral uninjured hemisphere. No evidence was obtained for any reorganization of stimulated motor responses in the injured hemisphere even in animals followed for as long as 475 days postinjury, suggesting other mechanisms underlying functional recovery. In intact cortex at some distance from contusion and laceration injuries, there was a marked elevation of thresholds to evoke movements that returned to normal by 9-15 days postinjury. Some intact hindlimb responses were observed after contusion injury that were absent in animals after 15 days postinjury, indicating a slow-growing lesion after this type of trauma. Surprisingly, no elevation in thresholds was noted for ablation injuries up to the edge of the cavity at any time postinjury, indicating that threshold changes near the boundary may be uncorrelated with functional recovery.

Animals↗
PubMed2006

Differential effects of antipsychotic drugs on serotonin-1A receptor-mediated disruption of prepulse inhibition.

Serotonin-1A (5-HT(1A)) receptors have been implicated in the symptoms of schizophrenia. However, there is limited in vivo evidence for an interaction of antipsychotic drugs with 5-HT(1A) receptor-mediated behavioral effects. We therefore investigated in rats the action of several antipsychotic drugs on prepulse inhibition (PPI), a measure of sensorimotor gating that is deficient in schizophrenia. Disruption of PPI at the 100-ms interstimulus interval (ISI), but not the 30-ms ISI, was induced by treatment with 0.5 mg/kg 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), the 5-HT(1A) receptor agonist. In rats pretreated with 0.25 mg/kg haloperidol (4-[-4-(p-chlorophenyl)-4-hydroxypiperidino]-4'-fluoro butyrophenone) or raclopride [3,5-dichloro-N-(1-ethylpyrrolidin-2-ylmethyl)-2-hydroxy-6-methoxybenzamide tartrate], the disruption of PPI was no longer significant. Of the atypical antipsychotic drugs clozapine (8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]-diazepine), olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine), risperidone [3-[2-[-4-(6-fluoro-1,2-benzisoxazol-3-yl) piperidino] ethyl-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one)], amisulpride (4-amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-o-anisamide), and aripiprazole (7-[4-[-4[-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydrocarbostyrilor 7-[4-[4-(2,3-dichlorophenyl) piperazin-1-yl]butoxy]-1,2,3,4,-tetrahydroquinolin-2-one), only aripiprazole significantly reduced the effect of 8-OH-DPAT on PPI. This effect was mimicked by pretreatment with the 5-HT(1A) receptor partial agonist, buspirone [N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dione hydrochloride]. On the other hand, some of the antipsychotic drugs and other pretreatments showed complex, prepulse-dependent effects on their own. These data show little in vivo interaction of several atypical antipsychotic drugs with the disruption of PPI mediated by 5-HT(1A) receptor stimulation. The action of haloperidol and raclopride suggests a major involvement of dopamine D(2) receptors in this effect, possibly downstream from the initial serotonergic stimulation. The action of aripiprazole could be mediated by its partial agonist properties at 5-HT(1A) receptors or its dopamine D(2)-blocking properties.

Acoustic Stimulation↗
PubMed2002

Regulation of early embryonic behavior by nitric oxide in the pond snail Helisoma trivolvis.

Helisoma trivolvis embryos display a cilia-driven rotational behavior that is regulated by a pair of serotonergic neurons named ENC1s. As these cilio-excitatory motor neurons contain an apical dendrite ending in a chemosensory dendritic knob at the embryonic surface, they probably function as sensorimotor neurons. Given that nitric oxide (NO) is often associated with sensory neurons in invertebrates, and has also been implicated in the control of ciliary activity, we examined the expression of NO synthase (NOS) activity and possible function of NO in regulating the rotational behavior in H. trivolvis embryos. NADPH diaphorase histochemistry on stage E25-E30 embryos revealed NOS expression in the protonephridia, buccal mass, dorsolateral ciliary cells and the sensory dendritic knobs of ENC1. At stages E35-40, the pedal ciliary cells and ENC1's soma, apical dendrite and proximal descending axon were also stained. In stage E25 embryos, optimal doses of the NO donors SNAP and SNP increased the rate of embryonic rotation by twofold, in contrast to the fourfold increase caused by 100 micro mol l(-1) serotonin. The NOS inhibitors L-NAME (10 mmol l(-1)) and 7-NI (100 micro mol l(-1)) decreased the rotation rate by approximately 50%, whereas co-addition of L-NAME and SNAP caused a twofold increase. In an analysis of the surge and inter-surge subcomponents of the rotational behavior, the NO donors increased the inter-surge rotation rate and the surge amplitude. In contrast, the NO inhibitors decreased the inter-surge rotation rate and the frequency of surges. These data suggest that the embryonic rotational behavior depends in part on the constitutive excitatory actions of NO on ENC1 and ciliary cells.

Animals↗