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PubMed2002

Behavioral neuroendocrinology of vasotocin and vasopressin and the sensorimotor processing hypothesis.

Vasotocin (AVT) and vasopressin (AVP) are potent modulators of social behaviors in diverse species of vertebrates. This review addresses questions about how and where AVT and AVP act to modulate social behaviors, focusing on research with an amphibian model (Taricha granulosa). In general, the behaviorally important AVT and AVP neurons occur in the forebrain and project to sites throughout the brain. Social behaviors are modulated by AVT and AVP acting at multiple sites in the brain and at multiple levels in the behavioral sequence. This review proposes that AVT and AVP can act on sensory pathways to modulate the responsiveness of neurons to behaviorally relevant sensory stimuli and also can act on motor pathways in the brainstem and spinal cord to modulate the neuronal output to behavior-specific pattern generators. This neurobehavioral model, in which AVT and AVP are thought to modulate social behaviors by affecting sensorimotor processing, warrants further research.

Animals↗
PubMed1998

Plasticity of primary somatosensory cortex paralleling sensorimotor skill recovery from stroke in adult monkeys.

Adult owl and squirrel monkeys were trained to master a small-object retrieval sensorimotor skill. Behavioral observations along with positive changes in the cortical area 3b representations of specific skin surfaces implicated specific glabrous finger inputs as important contributors to skill acquisition. The area 3b zones over which behaviorally important surfaces were represented were destroyed by microlesions, which resulted in a degradation of movements that had been developed in the earlier skill acquisition. Monkeys were then retrained at the same behavioral task. They could initially perform it reasonably well using the stereotyped movements that they had learned in prelesion training, although they acted as if key finger surfaces were insensate. However, monkeys soon initiated alternative strategies for small object retrieval that resulted in a performance drop. Over several- to many-week-long period, monkeys again used the fingers for object retrieval that had been used successfully before the lesion, and reacquired the sensorimotor skill. Detailed maps of the representations of the hands in SI somatosensory cortical fields 3b, 3a, and 1 were derived after postlesion functional recovery. Control maps were derived in the same hemispheres before lesions, and in opposite hemispheres. Among other findings, these studies revealed the following 1) there was a postlesion reemergence of the representation of the fingertips engaged in the behavior in novel locations in area 3b in two of five monkeys and a less substantial change in the representation of the hand in the intact parts of area 3b in three of five monkeys. 2) There was a striking emergence of a new representation of the cutaneous fingertips in area 3a in four of five monkeys, predominantly within zones that had formerly been excited only by proprioceptive inputs. This new cutaneous fingertip representation disproportionately represented behaviorally crucial fingertips. 3) There was an approximately two times enlargement of the representation of the fingers recorded in cortical area 1 in postlesion monkeys. The specific finger surfaces employed in small-object retrieval were differentially enlarged in representation. 4) Multiple-digit receptive fields were recorded at a majority of emergent, cutaneous area 3a sites in all monkeys and at a substantial number of area 1 sites in three of five postlesion monkeys. Such fields were uncommon in area 1 in control maps. 5) Single receptive fields and the component fields of multiple-digit fields in postlesion representations were within normal receptive field size ranges. 6) No significant changes were recorded in the SI hand representations in the opposite (untrained, intact) control hemisphere. These findings are consistent with "substitution" and "vicariation" (adaptive plasticity) models of recovery from brain damage and stroke.

Analysis of Variance↗
PubMed1996

Detailed behavioral analysis of water maze acquisition under APV or CNQX: contribution of sensorimotor disturbances to drug-induced acquisition deficits.

N-methyl-D-aspartate (NMDA) receptor antagonists disrupt acquisition of the water maze and cause sensorimotor disturbances. In a detailed behavioral analysis in male rats, it was found that the NMDA antagonist DL-2-aminophosphonovaleric acid (APV) caused sensorimotor disturbances in behaviors required for maze performance and that these correlated with acquisition impairments in both hidden and visible platform versions of the maze. Behavioral disturbances included thigmotaxic swimming, swimming over and deflecting off the platform, abnormal swim behavior, and hyperactivity. Rats familiar with the behavioral strategies involved in the task performed normally under APV. The results are consistent with the known role of NMDA receptors in sensorimotor mechanisms and suggest that drug-induced sensorimotor disturbances contributed to poor acquisition scores in naive rats. NMDA may contribute to but does not appear to be essential for spatial learning in the water maze.

2-Amino-5-phosphonovalerate↗
PubMed2006

Reduced functional deficits, neuroinflammation, and secondary tissue damage after treatment of stroke by nonerythropoietic erythropoietin derivatives.

Carbamylerythropoietin (CEPO) does not bind to the classical erythropoietin (EPO) receptor. Nevertheless, similarly to EPO, CEPO promotes neuroprotection on the histologic level in short-term stroke models. In the present study, we investigated whether CEPO and other nonerythropoietic EPO analogs could enhance functional recovery and promote long-term histologic protection after experimental focal cerebral ischemia. Rats were treated with the compounds after focal cerebral ischemia. Animals survived 1, 7, or 60 days and underwent behavioral testing (sensorimotor and foot-fault tests). Brain sections were stained and analyzed for Iba-1, myeloperoxidase, Tau-1, CD68 (ED1), glial fibrillary acidic protein (GFAP), Fluoro-Jade B staining, and overall infarct volumes. Treatment with CEPO reduced perifocal microglial activation (P<0.05), polymorphomonuclear cell infiltration (P<0.05), and white matter damage (P<0.01) at 1 day after occlusion. Carbamylerythropoietin-treated rats showed better functional recovery relative to vehicle-treated animals as assessed 1, 7, 14, 28, and 50 days after stroke. Both GFAP and CD68 were decreased within the ipsilateral thalamus of CEPO-treated animals 60 days postoperatively (P<0.01 and P<0.05, respectively). Furthermore, behavioral analysis showed efficacy of CEPO treatment even if administered 24 h after the stroke. Other nonerythropoietic derivatives such as carbamylated darbepoetin alfa and the mutant EPO-S100E were also found to protect against ischemic damage and to improve postischemic neurologic function. In conclusion, these results show that postischemic intravenous treatment with nonerythropoietic EPO derivatives leads to improved functional recovery, which may be linked to their long-term effects against neuroinflammation and secondary tissue damage.

Animals↗
PubMed2004

The selective serotonin-2A receptor antagonist M100907 reverses behavioral deficits in dopamine transporter knockout mice.

A hyperdopaminergic state in humans has been hypothesized to contribute to the pathology of a number of psychiatric illnesses, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Mice that display elevated synaptic levels of dopamine due to a genetically engineered deletion of the dopamine transporter (DAT) model behavioral deficits that simulate the above conditions. As novel treatment strategies for these disorders have focused on the serotonin (5-HT) 2A receptor, we determined the capacity of the highly selective 5-HT(2A) receptor antagonist M100907 to reverse behavioral deficits in DAT knockout (KO) mice. Prior to drug treatment, DAT KO mice exhibited increased levels of locomotor activity and highly linearized movement in a novel environment, as well as reduced prepulse inhibition (PPI) of acoustic startle, compared to wild-type littermates. Treatment with M100907 (0.3-1.0 mg/kg, but not 0.1 mg/kg) reversed locomotor deficits in DAT KO mice. Similarly, treatment with 1.0 mg/kg M100907 reversed the PPI deficits in DAT KO mice. These data indicate that selective 5-HT(2A) receptor antagonists, such as M100907, may represent a class of drugs that can be used to treat conditions in which a chronic, elevated dopaminergic tone is present and contributes to abnormal behavior and sensorimotor gating deficits.

Acoustic Stimulation↗
PubMed1985

Comparison of electrolytic and ibotenic acid lesions in the lateral hypothalamus.

Electrolytic lesions in the lateral hypothalamus (LH) seriously affect ingestive behavior and sensorimotor functions in the rat. We here report that bilateral infusions of the neurotoxin, ibotenic acid (IBO) in the LH yield a decrease in body weight, but not to the same extent as electrolytic lesions. The sensorimotor impairments were most severe after electrolytic lesions. When tested in a residential maze on days 5-7 and 18-20 after surgery, both lesioned groups showed no lack of motivation to seek food and water. Histological examination of the LH following IBO exposure revealed extensive degeneration of neuronal cell bodies with little evidence of non-specific damage. Biochemical analysis of the rostral forebrain content of norepinephrine (NE) and serotonin (5-HT) revealed that the fibers passing through the LH remained largely intact in the IBO treated rats. The results suggest that the observed aphagia and adipsia is not due to a lack of motivation, but rather reflects changes in the process which operate to initiate eating and drinking. Furthermore, selective neuronal degeneration induced the same behavioral changes as the electrolytic ones, though not to the same extent.

Animals↗
PubMed2002

The cerebellum: it's about time! But timing is not everything--new insights into the role of the cerebellum in timing motor and cognitive tasks.

Converging evidence from different research studies supports a role for the cerebellum in timing neural processes. The cerebellum is part of a distributed system for motor control. The timing hypothesis provides a specific functional role for the unique contribution of the cerebellum. The timing capabilities of the cerebellum appear to extend beyond motor control into tasks focusing on perceptual processing that require the precise representation of temporal information and sensorimotor learning. Behavioral and modeling studies suggest that the cerebellar timing system is best characterized as providing a near-infinite set of interval-type timers rather than as a single clock with pacemaker or oscillatory properties, but this is controversial. In addition to learning precisely timed motor responses, the cerebellum is involved in on-line processing using feed-forward systems for which sensory input is used prior to movement execution to improve movement accuracy. This would be a mechanism for triggering accurate "time." The cerebellum continues to fascinate scientists, and although survival is possible without the cerebellum, the resultant quality of life is significantly compromised with clumsiness, ataxia, hypotonia, dysarthria, slowing of various cognitive perceptual processes, and impaired fine motor and ocular-motor coordination. The last three decades have seen the development of research that has focused on how the cerebellum functions. Further neurophysiologic research in cerebellar cortical neurotransmission is likely to further our understanding of the cerebellar contribution to timing sensorimotor processes.

Animals↗
PubMedDate not supplied

Neurochemical mechanisms of the involvement of cortical sensorimotor neurons in alimentary and orientational behavior.

The object of these experiments was the study of the features of the neurochemical mechanisms of the involvement of individual neurons of the sensorimotor cortex of the rabbit brain the orienting reaction and the goal-oriented alimentary behavior elicited by stimulation of the "hunger center" of the lateral hypothalamus using electrical current of varying intensity. It is demonstrated that the neurotransmitters acetylcholine and norepinephrine, in approximately equal percentages, reorganize the reaction of neurons at the subthreshold as much as at the threshold level of stimulation. The microiontophoretic application to cortical sensorimotor neurons of the protein synthesis blocker, cycloheximide, also elicits alterations in their reactions to threshold and subthreshold stimulation of the lateral hypothalamus which are apparently linked to the suppression of synthesis of neuropeptides specific to both behaviors. It is proposed that the orienting, and especially the alimentary, motivational reactions are achieved by the activation of the synthesis of specific peptide molecules in the cortical sensorimotor neurons, which in fact may induce a change in their sensitivity to neurotransmitters.

Acetylcholine↗
PubMed2006

Steering by hearing: a bat's acoustic gaze is linked to its flight motor output by a delayed, adaptive linear law.

Adaptive behaviors require sensorimotor computations that convert information represented initially in sensory coordinates to commands for action in motor coordinates. Fundamental to these computations is the relationship between the region of the environment sensed by the animal (gaze) and the animal's locomotor plan. Studies of visually guided animals have revealed an anticipatory relationship between gaze direction and the locomotor plan during target-directed locomotion. Here, we study an acoustically guided animal, an echolocating bat, and relate acoustic gaze (direction of the sonar beam) to flight planning as the bat searches for and intercepts insect prey. We show differences in the relationship between gaze and locomotion as the bat progresses through different phases of insect pursuit. We define acoustic gaze angle, theta(gaze), to be the angle between the sonar beam axis and the bat's flight path. We show that there is a strong linear linkage between acoustic gaze angle at time t [theta(gaze)(t)] and flight turn rate at time t + tau into the future [theta(flight) (t + tau)], which can be expressed by the formula theta(flight) (t + tau) = ktheta(gaze)(t). The gain, k, of this linkage depends on the bat's behavioral state, which is indexed by its sonar pulse rate. For high pulse rates, associated with insect attacking behavior, k is twice as high compared with low pulse rates, associated with searching behavior. We suggest that this adjustable linkage between acoustic gaze and motor output in a flying echolocating bat simplifies the transformation of auditory information to flight motor commands.

Animals↗
PubMed1984

Effect of dopamine-depleting brain lesions on suckling and weaning in rats.

Rats given large dopamine-depleting brain lesions as adults exhibit severe impairments in ingestive behavior and sensorimotor function. In contrast to these well-known effects, virtually complete destruction of central dopaminergic neurons produced no such dysfunctions when it occurred in neonates. Indeed, rats continued to suckle and grow, albeit somewhat more slowly, and they could be weaned readily when they were 27 days old. Although most brain-damaged animals did not survive weaning when they were 18 days old, whereas controls exhibited no difficulty, this failure appears to be the consequence of their reduced body weight and related inability to maintain body temperature in a relatively cool environment (22 degrees C). Such premature weaning occurred more successfully when growth was stimulated by rearing brain-damaged pups in small litters or when ambient temperatures were raised to 31 degrees C so as to minimize heat loss. These results demonstrate that the effects of near-total dopamine-depleting brain lesions are considerably less severe when they occur in infants than when they occur in adults, and, consequently, they reveal a capacity for neural plasticity during development that is no longer present at maturity.

Animals↗
PubMed2005

Anatomical analysis of an aye-aye brain (Daubentonia madagascariensis, primates: Prosimii) combining histology, structural magnetic resonance imaging, and diffusion-tensor imaging.

This report presents initial results of a multimodal analysis of tissue volume and microstructure in the brain of an aye-aye (Daubentonia madagascariensis). The left hemisphere of an aye-aye brain was scanned using T2-weighted structural magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI) prior to histological processing and staining for Nissl substance and myelinated fibers. The objectives of the experiment were to estimate the volume of gross brain regions for comparison with published data on other prosimians and to validate DTI data on fiber anisotropy with histological measurements of fiber spread. Measurements of brain structure volumes in the specimen are consistent with those reported in the literature: the aye-aye has a very large brain for its body size, a reduced volume of visual structures (V1 and LGN), and an increased volume of the olfactory lobe. This trade-off between visual and olfactory reliance is likely a reflection of the nocturnal extractive foraging behavior practiced by Daubentonia. Additionally, frontal cortex volume is large in the aye-aye, a feature that may also be related to its complex foraging behavior and sensorimotor demands. Analysis of DTI data in the anterior cingulum bundle demonstrates a strong correlation between fiber spread as measured from histological sections and fiber spread as measured from DTI. These results represent the first quantitative comparison of DTI data and fiber-stained histology in the brain.

Animals↗
PubMed1998

Striatal glutamate antagonism induces contralateral neglect.

To assess the role of striatal glutamatergic synapses in mediating sensorimotor orientation behavior, glutamate receptor antagonists were infused into the left striatum of awake rats and behavioral orientation to contralateral and ipsilateral stimuli were quantified. The AMPA-kainate antagonist, DNQX, and the NMDA antagonist, CPP, both induced a large asymmetry in responding, such that the rats oriented much less to stimuli presented contralateral to the antagonist infusions. Furthermore, intrastriatal glutamate antagonist infusions increased the occurrence of incorrect responses, or turning away from a contralaterally-presented stimulus. In a separate experiment, intrastriatal DNQX was shown to block kainic acid (KA)-induced Fos expression in the striatum, but not in adjacent cerebral cortex, suggesting that the diffusion of this drug is restricted to the striatum.

Acoustic Stimulation↗
PubMed2002

Phase correction in sensorimotor synchronization: nonlinearities in voluntary and involuntary responses to perturbations.

When finger taps are synchronized with an auditory sequence, both a global phase shift (PS) and a local event onset shift (EOS) in the sequence elicit a phase correction response (PCR) on the next tap. The PCR to an expected PS is intended and large, whereas that to an expected EOS is unintended and smaller. PCR magnitude increases linearly with perturbation magnitude up to about +/-15% of the sequence period (500 milliseconds). With larger perturbations, voluntary PCRs increase more slowly whereas involuntary PCRs reach an asymptote. These results, obtained previously in a blocked design [J. Exp. Psychol. Human Percept. Perform. (in press)], were replicated in a randomized design and in two additional task contexts that varied participants' intentions while neutralizing their expectations. Neither design nor expectations seemed to play a role. However, considerable individual differences were noted. The results confirm that phase correction is partially automatic and partially subject to voluntary control, and they provide empirical estimates of error correction functions that may be useful in formal modeling of sensorimotor synchronization behavior.

Adult↗
PubMed2002

Thirteen-week oral toxicity study of synthetic lycopene products in rats.

Synthetic crystalline lycopene provides an alternative to extracts of naturally occurring lycopene for use in dietary supplements and functional foods. BASF Lycopene 10 CWD and Lyco Vit 10% formulated products each contain approximately 10% synthetic lycopene. These products were evaluated for toxicological and behavioral effects during a 13-week oral dosing study with male and female Wistar rats. Doses of 0, 500, 1500 and 3000 mg/kg body weight/day Lycopene CWD and 3000 mg/kg body weight /day Lyco Vit, as well as 3000 mg/kg body weight /day of the matrices used to formulate and stabilize each product, were administered by gavage to 10 rats/sex/day. A satellite group of five rats/sex received 0 or 3000 mg/kg body weight /day of each formulated product for an interim evaluation at 4 weeks of feeding. No statistically significant, dose-related effects on body weight, body weight gain, food consumption, hematology, urinalysis, clinical chemistry or ophthalmoscopic parameters were seen in any of the lycopene product or lycopene formulation matrix groups in comparison to the vehicle control group after 4 or 13 weeks of dosing. No deaths attributed to the test articles occurred during the study and the only clinical finding and at necropsy was the presence of red pigment in the feces and gastrointestinal tract that was associated with the red-pigmented test materials. No significant or dose-related abnormalities were found at necropsy or in microscopic evaluations of tissues collected at termination. Rats evaluated in home cages or in open field tests for behavioral and sensorimotor effects during the final week of the study showed no signs of treatment-related effects. The no-observed-adverse-effect level (NOAEL) for this study was concluded to be 3000 mg/kg body weight/day for both Lycopene CWD and Lyco Vit. The results of this study thus demonstrate the absence of any significant toxicological findings with Lycopene CWD and Lyco Vit products even at very high dose levels.

Administration, Oral↗
PubMed2003

Vascular syndromes of the thalamus.

BACKGROUND: This article reviews the anatomy, connections, and functions of the thalamic nuclei, their vascular supply, and the clinical syndromes that result from thalamic infarction. SUMMARY OF REVIEW: Thalamic nuclei are composed of 5 major functional classes: reticular and intralaminar nuclei that subserve arousal and nociception; sensory nuclei in all major domains; effector nuclei concerned with motor function and aspects of language; associative nuclei that participate in high-level cognitive functions; and limbic nuclei concerned with mood and motivation. Vascular lesions destroy these nuclei in different combinations and produce sensorimotor and behavioral syndromes depending on which nuclei are involved. Tuberothalamic territory strokes produce impairments of arousal and orientation, learning and memory, personality, and executive function; superimposition of temporally unrelated information; and emotional facial paresis. Paramedian infarcts cause decreased arousal, particularly if the lesion is bilateral, and impaired learning and memory. Autobiographical memory impairment and executive failure result from lesions in either of these vascular territories. Language deficits result from left paramedian lesions and from left tuberothalamic lesions that include the ventrolateral nucleus. Right thalamic lesions in both these vascular territories produce visual-spatial deficits, including hemispatial neglect. Inferolateral territory strokes produce contralateral hemisensory loss, hemiparesis and hemiataxia, and pain syndromes that are more common after right thalamic lesions. Posterior choroidal lesions result in visual field deficits, variable sensory loss, weakness, dystonia, tremors, and occasionally amnesia and language impairment. CONCLUSIONS: These vascular syndromes reflect the reciprocal cerebral cortical-thalamic connections that have been interrupted and provide insights into the functional properties of the thalamus.

Animals↗
PubMedDate not supplied

Flexible couplings: diffusing neuromodulators and adaptive robotics.

Recent years have seen the discovery of freely diffusing gaseous neurotransmitters, such as nitric oxide (NO), in biological nervous systems. A type of artificial neural network (ANN) inspired by such gaseous signaling, the GasNet, has previously been shown to be more evolvable than traditional ANNs when used as an artificial nervous system in an evolutionary robotics setting, where evolvability means consistent speed to very good solutions--here, appropriate sensorimotor behavior-generating systems. We present two new versions of the GasNet, which take further inspiration from the properties of neuronal gaseous signaling. The plexus model is inspired by the extraordinary NO-producing cortical plexus structure of neural fibers and the properties of the diffusing NO signal it generates. The receptor model is inspired by the mediating action of eurotransmitter receptors. Both models are shown to significantly further improve evolvability. We describe a series of analyses suggesting that the reasons for the increase in evolvability are related to the flexible loose coupling of distinct signaling mechanisms, one "chemical" and one "electrical."

Adaptation, Physiological↗
PubMedDate not supplied

The redefinition of failure to thrive from a case study perspective.

Explaining failure to thrive (FTT) in dichotomous terms--organic versus non-organic --no longer applies in the context of modern pediatric nursing. FTT has turned out to be much more multifaceted. One infant's story illustrates the complexities and long-term ramifications of a pediatric feeding disorder and the challenges faced by health care professionals and families in their care. The story illustrates how physiologic, sensorimotor, and behavioral issues can all impact a child's inability to gain weight as expected. With greater understanding, pediatric nurses can appreciate their role as members of a multidisciplinary pediatric feeding disorder team.

Breast Feeding↗