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PubMed2003

Somatosensory organization and behavior in naked mole-rats I: vibrissa-like body hairs comprise a sensory array that mediates orientation to tactile stimuli.

Orientation guided by mechanosensory stimuli is a fundamental behavior that has been analyzed most effectively in simple systems, but has been difficult to assess in mammals. This study demonstrates that sparsely distributed sensory 'hairs' on the body of naked mole-rats provide an ideal detector array for the assessment of touch guided orienting behavior. Naked mole-rats are fully subterranean rodents that are functionally blind and lack fur. About 40 tactile hairs (resembling facial vibrissae) are found on each side of the body, and they are systematically organized in a grid-like pattern from head to tail. Deflection of a single body hair triggered a highly accurate orientation of the snout toward the point of stimulation, thus topographically organized motor behavior can be elicited from this sensory array. This orienting behavior is specific to the body hair system: touch of intervening skin evoked responses less reliably, and observed responses were not topographically organized. Orientation elicited from this array was accurate regardless of the head-to-body position at the time of hair stimulation indicating that the orienting motor score takes relative head position into account. The consistent pattern of these hairs coupled with robust orienting behavior indicates that this mammalian model provides an appropriately simple system for analyzing the neuronal basis of sensorimotor integration involved in tactile orienting behavior.

Animals↗
PubMed1988

Seizures and recovery from experimental brain damage.

The effects of the gamma-aminobutyric acid antagonist, pentylenetetrazol (PTZ), on recovery from somatosensory and motor asymmetries after unilateral sensorimotor cortex lesions were investigated. Behavior was assessed using a bilateral tactile stimulation test and a measure of forelimb motor coordination. Immediately after surgery, the PTZ-treated and saline (SAL) control groups both exhibited severe ipsilateral behavioral asymmetries. Rats receiving PTZ recovered significantly faster from somatosensory asymmetry than those receiving SAL. Recovery was complete in the PTZ group within 3 postoperative weeks, while the SAL group failed to reach a comparable level until 2 months after surgery. There was no difference between PTZ and SAL groups on recovery of forelimb motor coordination. No difference in lesion size between the SAL and the PTZ groups could be found. These data are consistent with the hypothesis that post-traumatic neuronal depression may contribute to the severity of sensorimotor deficits observed after brain damage.

Animals↗
PubMed2006

Facilitation of saccadic eye movements by postsaccadic electrical stimulation in the primate caudate.

Sensorimotor experience followed by positive feedback leads to motor learning. Although the striatum, an input channel of the basal ganglia, has been implicated to play a key role in motor learning, little is known about how reward information modulates the neuronal processes in the striatum that causes behavioral changes. Here, we report that direct manipulation of the neuronal signal in the primate caudate yields behavioral changes comparable with those induced by natural reward. Electrical stimulation in the oculomotor region of the caudate immediately after saccades to a fixed direction led to selective facilitation of saccades in that direction. The facilitation remained even after stimulation was stopped, indicating a plastic change. These effects were observed when stimulation was applied after, not before, saccades. We propose that the caudate plays a causal role in behavioral changes by integrating selective sensorimotor and reward information in a temporally specific manner.

Animals↗
PubMed2004

Cardiac arrest/cardiopulmonary resuscitation increases anxiety-like behavior and decreases social interaction.

Advances in medical technology have increased the number of individuals who survive cardiac arrest/cardiopulmonary resuscitation (CPR). This increased incidence of survival has created a population of patients with behavioral and physiologic impairments. We used temperature manipulations to characterize the contribution of central nervous system damage to behavioral deficits elicited by 8 minutes of cardiac arrest/CPR in a mouse model. Once sensorimotor deficits were resolved, we examined anxiety-like behavior with the elevated plus maze and social interaction with an ovariectomized female. We hypothesized that anxiety-like behavior would increase and social interaction would decrease in mice subjected to cardiac arrest/CPR and that these changes would be attributable to central nervous system damage rather than damage to peripheral organs or changes orchestrated by the administration of epinephrine. Mice that were subjected to cardiac arrest/CPR while the peripheral organs, but not the brain, were protected by hypothermia exhibited increased anxiety-like behavior and decreased social interaction, whereas mice with hypothermic brains and peripheral organs during cardiac arrest/CPR did not exhibit behavioral impairments. The present study demonstrates that central nervous system damage from cardiac arrest/CPR results in increased anxiety and decreased social interaction and that these behavioral changes are not attributed to underlying sensorimotor deficits, dynamics of arrest and CPR, or peripheral organ damage.

Animals↗
PubMed2000

Processing spatial information in the sensorimotor branch of the visual system.

We distinguish two representations of visual space: a cognitive representation drives perception, and a sensorimotor representation controls visually guided behavior. Spatial values in the two representations are separated with the Roelofs effect: a target within an off-center frame appears biased in a location opposite the direction of the frame. The effect appears for a verbal measure (cognitive) but not for a jab at the target (sensorimotor). A 2-s response delay induces a Roelofs effect in the motor measure, showing the limit of motor memory. Motor error is not correlated with reaction time. Subjects could strike one of two identical targets, a process involving choice, without intrusion of a Roelofs effect, showing that the sensorimotor system can use its own coordinates even when a cognitive choice initiates the motor processing.

Cognition↗
PubMed2000

Behavior and mutagenesis screens: the importance of baseline analysis of inbred strains.

Random mutagenesis as a means of identifying the function of genes has been used extensively in a variety of model organisms. Until recently it has been used primarily in the identification of single-gene traits that cause visible and developmental mutations. However, this genetic approach also has the power to identify genes that control complex biological systems such as behavior. Mutagenesis screens for behavioral mutations require careful consideration of many factors, including choice of both assays and background strains for use in mutagenesis and subsequent mapping of the affected gene or genes. This paper describes behavioral assays for monitoring motor coordination on the accelerating rotarod, anxiety-related behaviors in the elevated zero maze and sensorimotor reactivity, gating, and habituation of acoustic startle. These five physiological or neurological behaviors can represent potential endophenotypes for a variety of neurological and psychiatric disorders. The significant degree of strain- and sex-specific differences in the performance of four inbred strains of mice (C57BL/6J, C3HeB/FeJ, DBA/2J, and 129/SvlmJ) in these behavioral assays illustrates the importance of performing baseline analysis prior to behavioral mutagenesis screens and genetic mapping of selected mutations.

Animals↗
PubMed2002

Rivastigmine antagonizes deficits in prepulse inhibition induced by selective immunolesioning of cholinergic neurons in nucleus basalis magnocellularis.

Impairments of cortical cholinergic inputs from the nucleus basalis magnocellularis fundamentally alter information processing and attentional function, thereby advancing the severity of psychopathology in major neuropsychiatric disorders. It was previously shown in adult rats that bilateral 192 IgG saporin-induced selective immunolesioning of the cholinergic neurons in the nucleus basalis produces pronounced and long-lasting deficits in sensorimotor gating measured by prepulse inhibition of the startle reflex. This behavioral paradigm is considered a valid model of sensorimotor gating deficits in the psychotic spectrum and efforts to analyze the significance of the cholinergic basal forebrain in this context are of great interest. In the present study the predictive value of the selective cholinergic immunolesioning model was tested by examining the ability of the cholinesterase inhibitor rivastigmine to restore prepulse inhibition in immunolesioned rats. We report here a pronounced restoring effect of acute (0.75 or 1.5 mg/kg s.c.) as well as repeated (0.75 mg/kg s.c. b.i.d., for 10 days) treatment with rivastigmine in this model of disrupted prepulse inhibition. Intra-nucleus basalis magnocellularis infusions of 192 IgG saporin resulted in extensive loss of basal-cortical cholinergic neurons as shown by the marked decrease in basal telencephalic choline acetyltransferase immunopositive neurons and cortical choline acetyltransferase activity. In this condition, rivastigmine was found to significantly increase cortical acetylcholine extracellular levels in lesioned animals measured by in vivo microdialysis. Taken together, our results strengthen the proposal that the nucleus basalis represents a critical station of the startle gating circuitry. In addition, our findings strongly indicate that even after dramatic decrease of cholinergic neurons, inhibition of acetylcholinesterase restores the cholinergic synaptic function to a point approaching normalization of experimentally induced psychopathology.

Acetylcholine↗
PubMed2005

Termination of pseudopregnancy in the rat alters the response to progesterone, chlordiazepoxide, and MK-801 in the elevated plus-maze.

RATIONALE: Allopregnanolone, a neurosteroid-reduced metabolite of progesterone, is a well-documented positive modulator of the gamma-aminobutyric type A (GABA(A)) receptor. As has been reported for other positive modulators of the GABA(A) receptor, chronic exposure to neurosteroids is hypothesized to decrease GABA(A) receptor function. Drawing from the literature on chronic exposure to benzodiazepines or alcohol, putative changes in N-methyl-D-aspartate (NMDA) receptor function are also expected after chronic neurosteroid exposure. OBJECTIVES: To assess the sensitivity of the GABA(A) and NMDA receptors after chronic elevation of neurosteroid produced by termination of pseudopregnancy in behavioral tests of anxiety and sensorimotor coordination. METHODS: Female rats ovariectomized on day 10 of pseudopregnancy were tested in the elevated plus-maze and on the rotor rod after an acute injection of progesterone (4 mg/0.2 ml, s.c.), chlordiazepoxide (5 or 15 mg/kg, i.p.), or MK-801 (0.025, 0.05, or 0.1 mg/kg, i.p.). RESULTS: Pseudopregnancy termination produced an anxiogenic-like response in the plus-maze; an acute injection of progesterone restored baseline levels of behavior in this test. Pseudopregnancy termination eliminated the anxiolytic-like, sedative, and ataxic effects of chlordiazepoxide. In contrast, pseudopregnancy termination produced an increased sensitivity to the anxiolytic-like and ataxic effects of MK-801. CONCLUSIONS: The effects of pseudopregnancy termination on the behavioral response to positive modulators of the GABA(A) receptor are consistent with results from studies in which chronic exposure to neurosteroids decreases the response to acute neurosteroid and benzodiazepine administration. However, unlike the enhanced glutamatergic tone resulting from discontinuation of chronic benzodiazepine or alcohol exposure, the termination of pseudopregnancy apparently decreases NMDA receptor function.

Animals↗
PubMed2004

Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein.

Accumulation of alpha-synuclein in brain is a hallmark of synucleinopathies, neurodegenerative diseases that include Parkinson's disease. Mice overexpressing alpha-synuclein under the Thy-1 promoter (ASO) show abnormal accumulation of alpha-synuclein in cortical and subcortical regions of the brain, including the substantia nigra. We examined the motor deficits in ASO mice with a battery of sensorimotor tests that are sensitive to alterations in the nigrostriatal dopaminergic system. Male wild-type and ASO mice were tested every 2 months for 8 months for motor performance and coordination on a challenging beam, inverted grid, and pole, sensorimotor deficits in an adhesive removal test, spontaneous activity in a cylinder, and gait. Fine motor skills were assessed by the ability to grasp cotton from a bin. ASO mice displayed significant impairments in motor performance and coordination and a reduction in spontaneous activity as early as 2 months of age. Motor performance and coordination impairments became progressively worse with age and sensorimotor deficits appeared at 6 months. Fine motor skills were altered at 4 months and worsened at 8 months. These data indicate that overexpression of alpha-synuclein induced an early and progressive behavioral phenotype that can be detected in multiple tests of sensorimotor function. These behavioral deficits provide a useful way to assess novel drug therapy in genetic models of synucleinopathies.

Animals↗
PubMed2000

Behavioral effects of protein deprivation and rehabilitation in adult rats: relevance to morphological alterations in the hippocampal formation.

In the present study we have analyzed the behavioral and neuroanatomical effects of protein deprivation in adult rats. Starting at 2 months of age, animals were maintained on 8%-casein diet either for 8 months (malnourished group), or for 6 months followed by a 2-month period of nutritional rehabilitation (17%-protein diet, rehabilitated group). Malnourished rats exhibited reduced emotional reactivity and impaired habituation in the open field. In a water maze, these animals did not differ from controls during training, but showed retention deficits on the probe trial. However, working memory, sensorimotor abilities and passive avoidance behavior were not significantly impaired in malnourished rats. The performance of rehabilitated group was similar to that of the control group throughout behavioral testing. Postmortem morphological analysis revealed that the total number of neurons in the granular layer of the dentate gyrus, and in CA3 and CA1 hippocampal fields was reduced in protein-deprived and rehabilitated rats relative to controls. In addition, it was found that protein deprivation caused a 30% loss of synapses established between mossy fibers and dendrites of CA3 pyramidal cells, whereas nutritional rehabilitation resulted in a reversal of this effect. These results show that prolonged malnutrition in adult rats produces marked loss of hippocampal neurons and synapses accompanied by substantial impairments of hippocampal-dependent behaviors. The fact that nutritional rehabilitation results in restoration of the total number of hippocampal synapses and parallel amelioration of the behavioral impairments suggests that the mature CNS possesses a remarkable potential for structural and functional recovery from the damage induced by this type of dietary insult.

Analysis of Variance↗
PubMed2004

Effects of riluzole on combined MPTP + 3-nitropropionic acid-induced mild to moderate striatonigral degeneration in mice.

We investigated the potency of riluzole, an anti-glutamatergic drug, to affect ongoing neuronal death process following combined MPTP + 3-nitropropionic acid (3-NP) intoxication producing combined striatal and nigral degeneration (SND) in mice. We used a "neuronal rescue" strategy by administering riluzole after the end of intoxication. The motor disorder, its recovery, behavioral performances at motor and sensorimotor integration tasks and histopathological outcome were compared in the saline and riluzole groups (10 mg/kg and 20 mg/kg), matched by triplets for motor severity. While riluzole did not produce any effect on the gross motor disorder nor on rotarod task, open-field kinetic variables or on the traversing beam task, it had a subtle effect on the performances at the pole test. The histopathological outcome was significantly better in the riluzole-treated mice regarding both nigral and dorsolateral striatal cell loss and astroglial activation, with a dose-effect relationship. Thus, riluzole has limited "neuronal rescue" properties from an histopathological point of view with a subtle motor behavior improvement in a MPTP + 3-NP-induced SND in mice.

Animals↗
PubMed2005

Mechanosensory properties in the human gastric antrum evaluated using B-mode ultrasonography during volume-controlled antral distension.

The aims of this study were to evaluate gastric antral mechanical behavior and distension-induced sensorimotor responses in the human gastric antrum using transabdominal ultrasound scanning. Ten healthy volunteers underwent volume-controlled ramp inflation of a bag located in the antrum with volumes up to 125 ml. The active and passive circumferential tensions and stresses were calculated from measurements of pressure, diameter, and wall thickness before and during the administration of the anticholinergic drug butylscopolamine. The bag distensions elicited contractions in the antrum and sensory responses below the pain threshold. Butylscopolamine abolished the contractions and significantly reduced the sensory response. The length-tension diagram known from in vitro studies of smooth muscle strips could be reproduced as tension-volume diagrams in the human gastric antrum. The number of induced contractions and the contraction pressure amplitude (afterload) showed a parabolic behavior as function of the distension volume (preload), with maximum approximately at 70 ml. At the sensation threshold, the luminal circumference showed the lowest variation coefficient (13-25%), whereas the variation coefficient was more than 100% for the pressure, tensions, and stresses. We conclude that the muscle length-tension diagram and typical preload-afterload curves ad modem the Frank-Starling cardiac law can be obtained in the human gastric antrum. The sensory responses were most closely associated with the luminal circumference, indicating that the sensation during antral distension depends on deformation rather than on tension.

Adult↗
PubMed2025

Toxicological Assessment of Melamine-Functionalized Graphene Oxide and Carbon Nanotubes Using Zebrafish Models.

Graphene oxide (GO) and carbon nanotube (CNT)-based nanomaterials have attracted significant interest in various industrial and biomedical applications due to their unique physicochemical properties; however, concerns about their potential toxicity, especially when modified with additives like melamine (M), remain largely unresolved. This study investigates the toxicological effects and underlying mechanisms of graphene oxide-melamine (GO-M) and carbon nanotube-melamine (CNT-M) nanoparticles in zebrafish (Danio rerio) embryos and larvae. To this end, developmental toxicity, phenotypic and behavioral changes, as well as histopathological and immunofluorescence alterations, were evaluated following acute exposure to GO-M and CNT-M nanoparticles at concentrations of 5, 10, and 20 mg/L. Results showed that both nanoparticles delayed larval hatching, particularly at higher concentrations (10 and 20 mg/L). Malformations were observed at 20 mg/L in the GO-M group and at 10 and 20 mg/L in the CNT-M group. Additionally, significant changes in larval length and eye area were observed at all concentrations for both nanoparticles. Behavioral assessments revealed that CNT-M exposure at 10 and 20 mg/L significantly impaired head sensorimotor reflexes, while all concentrations affected tail reflexes. In contrast, GO-M exposure did not significantly alter sensorimotor responses. These findings suggest differential toxic mechanisms and neurobehavioral effects of GO-M and CNT-M nanoparticles during early zebrafish development.

Animals↗
PubMed1996

Effects of preweaning environmental stimulation on neuronal and behavioral impairment produced by undernutrition.

The present study investigates the effects of sensorimotor stimulation on the basal dendrogenesis of superficial cerebrocortical neurons and the accomplishment in the associated exploratory behavior in rats simultaneously exposed to nutritional deprivation. Sprague-Dawley albino rats were submitted to nutritional-environmental influences from birth to the 21st postnatal day. Exploratory behavior was assessed by the evaluation of locomotor activity in the open-field apparatus. In order to evaluate changes in neuronal morphology induced by nutritional-environmental variables, brains were stained according to the Golgi-Cox-Sholl procedure. Dendritic development was assessed under camera lucida by measuring basal dendritic branching of layer II and III pyramidal neurons, located in the dorsomedial region of the visual cortex of the rat. Morphometrical analysis revealed that both basal dendritic length and branching were significantly reduced by undernutrition. In contrast, environmental stimulation during the suckling period compensated for the neuronal impairment produced by protein-calorie deprivation. An improvement was also observed in exploratory behavior although to a lesser degree, as shown by the open field test data. In conclusion, the present results indicate that sensorimotor stimulation applied during the period of fastest rate of cortical cytodifferentiation compensates for neuronal and behavioral impairment produced by undernutrition.

Animals↗
PubMed1998

Neurobehavioral effects of chronic ingestion of Great Lakes chinook salmon.

Cross-generational chronic feeding of either a 5 or a 20% lyophilized Lake Huron (LH) or Lake Ontario (LO) chinook salmon diet to rats caused no observable effects on many behavioral dimensions including activity, exploration, sensorimotor function, and stereotypy. As assessed by the Morris water maze and the radial arm maze, there was no diet-induced impairment of spatial learning or long-term memory. There was no evidence that the fish diets caused an exaggerated response to food reward reduction as had been observed previously for rats fed Oswego area Lake Ontario salmon. Effects of the fish diets with the exception of one statistically significant but probably meaningless effect on the Morris water maze for females were found only for male rats and only for males who ate the 20% diet. F1 male rats were reluctant to traverse a runway for a single pellet reward. Performance of the reference/working memory version of the radial arm maze was affected for the F1 LO-20 rats and for the F2 LH-20 rats. Until further research is conducted it would be unwise to ignore indications that male rats may show some effect of chronic consumption of the highest concentration of these diets, particularly on tasks that require intact frontocortical dopamine function.

Analysis of Variance↗
PubMed1999

Gradual emergence of song selectivity in sensorimotor structures of the male zebra finch song system.

Birdsong is a model system for understanding how motor and sensory information interact to coordinate behavior. Neurons in one potential site of sensorimotor integration, the forebrain nucleus HVc, have premotor activity during singing and auditory activity during playback of the bird's own song. It is not known whether the high degree of selectivity for learned features of song observed during playback arises in HVc or also in structures afferent to HVc. We recorded in anesthetized adult zebra finches from two structures afferent to HVc: either the nucleus interfacialis (NIf) or the L1 subdivision of the field L complex, and simultaneously from a second electrode in HVc. Correlations in the bursting pattern of ongoing activity of HVc and NIf recordings were observed; these helped to localize the first electrode to NIf recording sites. Most NIf neurons exhibited song-selective responses, but as a population, they were less selective than were HVc neurons. Most L1 neurons were not song-selective. NIf neurons have also been reported to have premotor activity during singing; thus, NIf is another potential site of auditory-motor interactions in the song system. Evidence gathered to date suggests that those brain areas in the passerine forebrain that are recruited during song production also display the most selective learned auditory responses.

Acoustic Stimulation↗
PubMed1997

Self-organized huddles of rat pups modeled by simple rules of individual behavior.

Starting at infancy and continuing throughout adult life, huddling is a major component of the behavioral repertoire of Norway rats (Rattus norvegicus). Huddling behavior maintains the cohesion of litters throughout early life, and in adulthood, it remains a consistent feature of social behavior of R. norvegicus. During infancy, rats have severely limited sensorimotor capabilities, and yet they are capable of aggregating and display a form of group regulatory behavior that conserves metabolic effort and augments body temperature regulation. The functions of huddling are generally understood as group adaptations, which are beyond the capabilities of the individual infant rat. We show, however, that huddling as aggregative or cohesive behavior can emerge as a self-organizing process from autonomous individuals following simple sensorimotor rules. In our model, two sets of sensorimotor parameters characterize the topotaxic responses and the dynamics of contact in 7-day-old rats. The first set of parameters are conditional probabilities of activity and inactivity given prior activity or inactivity and the second set are preferences for objects in the infant rat's environment. We found that the behavior of the model and of actual rat pups compare very favorably, demonstrating that the aggregative feature of huddling can emerge from the local sensorimotor interactions of individuals, and that complex group regulatory behaviors in infant rats may also emerge from self-organizing processes. We discuss the model and the underlying approach as a paradigm for investigating the dynamics of social interactions, group behavior, and developmental change.

Animals↗
PubMed2002

Dopamine in the nucleus accumbens: cellular actions, drug- and behavior-associated fluctuations, and a possible role in an organism's adaptive activity.

This review expounds the idea that the analysis of dopamine (DA) action on target cells under behaviorally relevant conditions and behavior-related changes in DA activity can offer new information to clarify the functional significance of mesocorticolimbic DA. In contrast to the traditional association of DA with certain behavioral processes and mechanisms (activation, arousal, conditioning, motivation, reinforcement, sensorimotor integration, etc.), evaluation of DA activity during well-controlled behaviors established by different reinforcers can provide important clues for determining the role of DA in the development and regulation of goal-directed behavior. This review summarizes the results of our microiontophoretic studies of striatal neurons in awake, unrestrained rats, particularly the action of DA on spontaneously active and glutamate (GLU)-stimulated cells, the pattern of DA-GLU interaction, and the role of tonic DA release in regulating the activity and afferent responsiveness of these units. We present the results of our iontophoretic studies of ventral tegmental area (VTA) neurons in freely moving animals suggesting the complexity and limitations in their identification as DA- and non-DA cells under behaviorally relevant conditions. We also consider technical and methodological problems related to electrophysiological and electrochemical evaluation of DA transmission in behaving animals. Finally, we discuss parallels and differences in the activity of presumed DA VTA neurons and changes of nucleus accumbens DA-dependent electrochemical signal during heroin self-administration (SA) behavior.

Animals↗