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PubMedDate not supplied

Opposing roles for dopamine and serotonin in the modulation of human spatial working memory functions.

Neurocognitive research has focused on monoaminergic influences over broad behavior patterns. For example, dopamine (DA) generally facilitates informational transfer within limbic and cortical networks to promote reward-seeking behavior. Specifically, DA activity in prefrontal cortex modulates the ability for nonhuman primates and humans to perform spatial working memory tasks. Serotonin (5HT) constrains the activity of DA, resulting in an opposing relationship between DA and 5HT with respect to emotional and motor behaviors. A role for 5HT in constraining prefrontally guided spatial working memory (WM) processes in humans has not been empirically demonstrated but is a logical avenue for study if these principles of neurotransmitter activity hold within cortical networks. In this study, normal humans completed a visuospatial WM task under pharmacological challenge with (i) bromocriptine, a DA agonist and (ii) fenfluramine, a serotonin agonist, in a double-blind, repeated-measures, placebo-controlled design. Findings indicate that bromocriptine facilitated spatial delayed, but not immediate, memory performance. Fenfluramine resulted in impaired delayed spatial memory. These effects were not due to nonspecific arousal, attentional, sensorimotor or perceptual changes. These findings suggest that monoaminergic neurotransmitters (DA and 5HT) may interact within cortical networks to modulate the expression of specific cognitive behaviors, particularly effortful processes associated with goal-directed activity.

Adult↗
PubMed2005

Modulation of behavior and cortical motor activity in healthy subjects by a chronic administration of a serotonin enhancer.

UNLABELLED: SSRIs are postulated to modulate motor behavior. A single dose of selective serotoninergic reuptake inhibitors (SSRIs) like fluoxetine, paroxetine, or fluvoxamine, has been shown to improve motor performance and efficiency of information processing for simple sensorimotor tasks in healthy subjects. At a cortical level, a single dose of SSRI was shown to induce a hyperactivation of the primary sensorimotor cortex (S1M1) involved in the movement (Loubinoux, I., Boulanouar, K., Ranjeva, J. P., Carel, C., Berry, I., Rascol, O., Celsis, P., and Chollet, F., 1999. Cerebral functional magnetic resonance imaging activation modulated by a single dose of the monoamine neurotransmission enhancers fluoxetine and fenozolone during hand sensorimotor tasks. J. Cereb. Blood Flow Metab. 19 1365--1375, Loubinoux, I., Pariente, J., Boulanouar, K., Carel, C., Manelfe, C., Rascol, O., Celsis, P., and Chollet, F., 2002. A Single Dose of Serotonin Neurotransmission Agonist Paroxetine Enhances Motor Output. A double-blind, placebo-controlled, fMRI study in healthy subjects. NeuroImage 15 26--36). Since SSRIs are usually given for several weeks, we assessed the behavioral and cerebral effects of a one-month chronic administration of paroxetine on a larger group. In a double-blind, placebo controlled and crossover study, 19 subjects received daily 20 mg paroxetine or placebo, respectively, over a period of 30 days separated by a wash-out period of 3 months. After each period, the subjects underwent an fMRI (active or passive movement, dexterity task, sensory discrimination task) and a behavioral evaluation. Concurrently, a TMS (transcranial magnetic stimulation) study was conducted (Gerdelat-Mas, A., Loubinoux, I., Tombari, D., Rascol, O., Chollet, F., Simonetta-Moreau, M., 2005. Chronic administration of selective serotonin re-uptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects. NeuroImage 27,314--322). RESULTS: On the one hand, paroxetine improved motor performances at the finger tapping test (P=0.02) without affecting choice reaction time, strength and dexterity significantly. Subjects were also faster in processing the spatial incongruency between a stimulus and the motor response (P=0.04). In order to differentiate behavioral components, a principal component analysis was performed on all motor tests, and several characteristics were differentiated: strength, speed, skill, attention, and motor response coding. Paroxetine would improve the efficiency of motor response coding (MANOVA on the factors; factor 3, P=0.01). On the other hand, the chronic administration induced a significant hypoactivation of S1M1 whatever the task: motor or sensory, simple or complex (random effect analysis, P<0.05). The hypoactivation correlated with the improvement of performances at the finger tapping test (P<0.05) suggesting more efficiency in cerebral motor processing. CONCLUSIONS: Our results showed a clear modulation of sensory and motor cerebral activation after a chronic paroxetine administration. An improvement in both behavior and cerebral efficiency was suggested. It could be hypothesized that monoamines, by an unspecific effect, may tune the response of pyramidal neurons to optimize performances.

Adult↗
PubMed1985

Long lasting behavioral effects of dimethyl sulfoxide and the "peripheral" toxicant p-bromophenylacetylurea.

Behavioral toxic effects caused by a relatively small dose of the "peripheral" neurotoxin, p-bromophenylacetylurea (BPAU), and of its vehicle, dimethyl sulfoxide (DMSO) were investigated. BPAU induces, in rats, a central-peripheral distal axonopathy similar to that produced in humans by toxic organophosphorus-containing compounds, and has been proposed as a model to study this type of toxicity in a convenient experimental mammal. Rats were injected with BPAU (50 or 100 mg/kg) in DMSO (1 ml/kg), with DMSO alone, or with saline. 100 mg BPAU/kg produced permanent weight loss and hind limb paresis; the low dose did not. Behavioral testing, 2 days to 4 mo post-treatment, indicated that DMSO and/or 50 mg/kg of BPAU retarded habituation of spontaneous exploratory activity, impaired acquisition of conditioned (auto-shaped) behavior, and changed the dose-response relationship ford-amphetamine-induced suppression of operant (fixed ratio 32) responding. BPAU-treated animals were also impaired in initial performance of operant behavior maintained by a fixed ratio schedule of reinforcement, at high (greater than or equal to FR 16) ratio values. Thus, neurobehavioral toxicity may occur at doses too low to induce organophosphorus-type sensorimotor impairment or pathology. Further, DMSO may also exert effects on neurobehavioral function, suggesting it too may be potentially toxic within this domain.

Animals↗
PubMed1997

Manuo-ocular coordination in target tracking. II. Comparing the model with human behavior.

Several studies have shown that humans track a moving visual target with their eyes better if the movement of this target is directly controlled by the observer's hand. The improvement in performance has been attributed to coordination control between the arm motor system and the smooth pursuit (SP) system. In such a task, the SP system shows characteristics that differ from those observed during eye-alone tracking: latency (between the target-arm and the eye motion onsets) is shorter, maximum SP velocity is higher and the maximum target motion frequency at which the SP can function effectively is also higher. The aim of this article is to qualitatively evaluate the behavior of a dynamical model simulating the oculomotor system and the arm motor system when both are involved in tracking visual targets. The evaluation is essentially based on a comparison of the behavior of the model with the behavior of human subjects tracking visual targets under different conditions. The model has been introduced and quantitatively evaluated in a companion paper. The model is based on an exchange of internal information between the two sensorimotor systems, mediated by sensory signals (vision, arm muscle proprioception) and motor signals (arm motor command copy). The exchange is achieved by a specialized structure of the central nervous system, previously identified as a part of the cerebellum. Computer simulation of the model yielded results that fit the behavior of human subjects observed during previously reported experiments, both qualitatively and quantitatively. The parallelism between physiology and human behavior on the one hand, and structure and simulation of the model on the other hand, is discussed.

Behavior↗
PubMedDate not supplied

Area-specific self-regulation of slow cortical potentials on the sagittal midline and its effects on behavior.

Exteroceptive feedback was given for negative and positive shifts in slow potentials (SPs) recorded from Fz, Cz, or Pz (between groups design). Slow potentials at the feedback site were referred to adjacent scalp and non-cephalic electrodes, so as to confine SP shifts to the feedback location. Area-specific regulation of SPs was obtained at each midsagittal site after 3 days of feedback training. Subjects reported sensorimotor and emotional arousal when negative SP shifts were trained frontally, but not when negative shifts were trained parietally (cognitive/attentional strategies reported after parietal feedback). Area-specific regulation of SPs was subsequently abolished when behavioral tasks were added to further probe frontal/parietal differences (dual-task procedure). These findings indicate that area-specific self-regulation of SPs is possible on the sagittal midline, and that self-regulated parietal SPs (in contrast to frontal ones) arise from non-motoric generators. The source of SP self-regulation was more readily probed by verbal reports of feedback strategy than by study of dual-task relations, because feedback control was disrupted by the dual-task requirement.

Adult↗
PubMed2006

Behavioral and physiological methods for early quantitative assessment of spinal cord injury and prognosis in rats.

Methods for reliable evaluation of spinal cord (SC) injury in rats at short periods (2 and 24 h) after lesion were tested to characterize the mechanisms implicated in primary SC damage. We measured the physiological changes occurring after several procedures for producing SC injury, with particular emphasis on sensorimotor functions. Segmental and suprasegmental reflexes were tested in 39 male Wistar rats weighing 250-300 g divided into three control groups that were subjected to a) anesthesia, b) dissection of soft prevertebral tissue, and c) laminectomy of the vertebral segments between T10 and L1. In the lesion group the SC was completely transected, hemisected or subjected to vertebral compression. All animals were evaluated 2 and 24 h after the experimental procedure by the hind limb motility index, Bohlman motor score, open-field, hot-plate, tail flick, and paw compression tests. The locomotion scale proved to be less sensitive than the sensorimotor tests. A reduction in exploratory movements was detected in the animals 24 h after the procedures. The hot-plate was the most sensitive test for detecting sensorimotor deficiencies following light, moderate or severe SC injury. The most sensitive and simplest test of reflex function was the hot-plate. The hemisection model promoted reproducible moderate SC injury which allowed us to quantify the resulting behavior and analyze the evolution of the lesion and its consequences during the first 24 h after injury. We conclude that hemisection permitted the quantitation of behavioral responses for evaluation of the development of deficits after lesions. Hind limb evaluation scores and spontaneous exploration events provided a sensitive index of immediate injury effects after SC lesion at 2 and 24 h. Taken together, locomotion scales, open-field, and hot-plate tests represent reproducible, quantitatively sensitive methods for detecting functional deficiencies within short periods of time, indicating their potential for the study of cellular mechanisms of primary injury and repair after traumatic SC injury.

Animals↗
PubMed2001

Habituation of the proleg withdrawal reflex in Manduca sexta does not involve changes in motoneuron properties or depression at the sensorimotor synapse.

Larvae of the hawkmoth, Manduca sexta, exhibit a defensive proleg withdrawal reflex in which deflection of mechanosensory hairs on the proleg tip (the planta) evokes retraction of the proleg. A previous behavioral study showed that this reflex habituates in response to repeated planta hair deflection and exhibits several other defining features of habituation. In a semi-intact preparation consisting of a proleg and its associated segmental ganglion, repeated deflection of a planta hair or electrical stimulation of its sensory neuron causes a neural correlate of habituation, manifested as a decrease in the number of action potentials evoked in the proleg motor nerve. Monosynaptic connections from planta hair sensory neurons to the principal planta retractor motoneuron exhibit several forms of activity-dependent plasticity. In the present study we recorded intracellularly from this motoneuron during repetitive electrical stimulation of a planta hair sensory neuron. The number of action potentials evoked in the motoneuron decreased significantly, representing a neural correlate of habituation. The motoneuron's resting membrane potential, input resistance. and spike threshold measured before and after repetitive stimulation did not differ between the stimulated group and a control group. Furthermore, the amplitude of the monosynaptic excitatory postsynaptic potential, as well as the magnitude of paired-pulse facilitation, evoked in the motoneuron by the sensory neuron did not change after repetitive stimulation. These results suggest that depression at the sensorimotor synapse does not contribute to reflex habituation. Rather, other mechanisms in the ganglion of the stimulated segment, such as changes in polysynaptic reflex pathways, appear to be responsible.

Animals↗
PubMed1999

The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking.

Studies addressing behavioral functions of dopamine (DA) in the nucleus accumbens septi (NAS) are reviewed. A role of NAS DA in reward has long been suggested. However, some investigators have questioned the role of NAS DA in rewarding effects because of its role in aversive contexts. As findings supporting the role of NAS DA in mediating aversively motivated behaviors accumulate, it is necessary to accommodate such data for understanding the role of NAS DA in behavior. The aim of the present paper is to provide a unifying interpretation that can account for the functions of NAS DA in a variety of behavioral contexts: (1) its role in appetitive behavioral arousal, (2) its role as a facilitator as well as an inducer of reward processes, and (3) its presently undefined role in aversive contexts. The present analysis suggests that NAS DA plays an important role in sensorimotor integrations that facilitate flexible approach responses. Flexible approach responses are contrasted with fixed instrumental approach responses (habits), which may involve the nigro-striatal DA system more than the meso-accumbens DA system. Functional properties of NAS DA transmission are considered in two stages: unconditioned behavioral invigoration effects and incentive learning effects. (1) When organisms are presented with salient stimuli (e.g., novel stimuli and incentive stimuli), NAS DA is released and invigorates flexible approach responses (invigoration effects). (2) When proximal exteroceptive receptors are stimulated by unconditioned stimuli, NAS DA is released and enables stimulus representations to acquire incentive properties within specific environmental context. It is important to make a distinction that NAS DA is a critical component for the conditional formation of incentive representations but not the retrieval of incentive stimuli or behavioral expressions based on over-learned incentive responses (i.e., habits). Nor is NAS DA essential for the cognitive perception of environmental stimuli. Therefore, even without normal NAS DA transmission, the habit response system still allows animals to perform instrumental responses given that the tasks take place in fixed environment. Such a role of NAS DA as an incentive-property constructor is not limited to appetitive contexts but also aversive contexts. This dual action of NAS DA in invigoration and incentive learning may explain the rewarding effects of NAS DA as well as other effects of NAS DA in a variety of contexts including avoidance and unconditioned/conditioned increases in open-field locomotor activity. Particularly, the present hypothesis offers the following interpretation for the finding that both conditioned and unconditioned aversive stimuli stimulate DA release in the NAS: NAS DA invigorates approach responses toward 'safety'. Moreover, NAS DA modulates incentive properties of the environment so that organisms emit approach responses toward 'safety' (i.e., avoidance responses) when animals later encounter similar environmental contexts. There may be no obligatory relationship between NAS DA release and positive subjective effects, even though these systems probably interact with other brain systems which can mediate such effects. The present conceptual framework may be valuable in understanding the dynamic interplay of NAS DA neurochemistry and behavior, both normal and pathophysiological.

Animals↗
PubMed2001

Sensorimotor adaptation to violations of temporal contiguity.

Most events are processed by a number of neural pathways. These pathways often differ considerably in processing speed. Thus, coherent perception requires some form of synchronization mechanism. Moreover, this mechanism must be flexible, because neural processing speed changes over the life of an organism. Here we provide behavioral evidence that humans can adapt to a new intersensory temporal relationship (which was artificially produced by delaying visual feedback). The conflict between these results and previous work that failed to find such improvements can be explained by considering the present results as a form of sensorimotor adaptation.

Adult↗
PubMed1983

Effects of hypothalamic stimulation on unit responses recorded from neurons of sensorimotor cortex of awake cats during conditioning.

1. The activity of single units of the coronal pericruciate (CPC) cortex was studied in 11 awake cats during sessions in which a click conditioned stimulus (CS) was repeatedly paired with glabella tap unconditioned stimulus (US) and hypothalamic stimulation (HS). Effects of HS on the activity of cortical units were also studied during sessions in which HS alone was delivered repeatedly every 10 s. 2. HS evoked an increase in spike activity of less than 60 ms latency in 89 of 116 units tested. 3. Repeated presentation of HS that was effective in producing rapid behavioral conditioning resulted in a characteristic reduction in the latency of discharge evoked by HS in cortical units. 4. Short-latency activation (less than 20 ms) of units of the sensorimotor cortex appeared to be characteristic of HS that led to enhanced rates of conditioned response (CR) acquisition. One of the cells responding in this way was identified as a pyramidal cell of layer V by intracellular injection of horseradish peroxidase (HRP). 5. Further analyses of activity were performed on 16 units of the CPC cortex that were followed through conditioning (or reconditioning) and extinction of the CR. After less than 10 CS-US-HS pairings, there was a selective augmentation of unit response to the CS but not of response to an explicitly unpaired discriminative stimulus (DS). Responses to the CS were not similarly augmented when presentations of HS preceded rather than followed the presentations of the CS and US. The rapid development of CS-evoked unit activity coincided with the rapid acquisition of discriminative CRs behaviorally. 6. During conditioning, the most conspicuous increases in CS-evoked unit response occurred at latencies 100 ms or more after onset of the click CS. This corresponded with the behavioral observation that the majority of eye blink CRs occurred with onset latencies longer than 100 ms.

Animals↗
PubMed2000

Representation, space and Hollywood Squares: looking at things that aren't there anymore.

It has been argued that the human cognitive system is capable of using spatial indexes or oculomotor coordinates to relieve working memory load (Ballard, D. H., Hayhoe, M. M., Pook, P. K., & Rao, R. P. N. (1997). Behavioral and Brain Sciences, 20(4), 723), track multiple moving items through occlusion (Scholl, D. J., & Pylyshyn, Z. W. (1999). Cognitive Psychology, 38, 259) or link incompatible cognitive and sensorimotor codes (Bridgeman, B., & Huemer, V. (1998). Consciousness and Cognition, 7, 454). Here we examine the use of such spatial information in memory for semantic information. Previous research has often focused on the role of task demands and the level of automaticity in the encoding of spatial location in memory tasks. We present five experiments where location is irrelevant to the task, and participants' encoding of spatial information is measured implicitly by their looking behavior during recall. In a paradigm developed from Spivey and Geng (Spivey, M. J., & Geng, J. (2000). submitted for publication), participants were presented with pieces of auditory, semantic information as part of an event occurring in one of four regions of a computer screen. In front of a blank grid, they were asked a question relating to one of those facts. Under certain conditions it was found that during the question period participants made significantly more saccades to the empty region of space where the semantic information had been previously presented. Our findings are discussed in relation to previous research on memory and spatial location, the dorsal and ventral streams of the visual system, and the notion of a cognitive-perceptual system using spatial indexes to exploit the stability of the external world.

Adult↗
PubMedDate not supplied

[The effect of serotonin antibodies on the behavior of C57Bl/6 mice in an open field and on the level of monoamines in the brain structures].

Mice of C57BL/6 strain were singly injected intraperitoneally with antibodies (AB) to serotonin (5-HT). The "open-field" testing in different periods after the AB injection revealed a depression of behavior within 1.5 h which changed for activation within 1 day and, again, depression within 5 days after the injection. The analysis of neurotransmitter content in the sensorimotor cortex and hypothalamus revealed increased levels of serotonin and, especially, dopamine in the cortex within 1 day. The cortex serotonin level within 5 days was also increased. The possible mechanisms are discussed of neurotropic action of AB to 5-HT.

Animals↗
PubMedDate not supplied

[The characteristics of the learning and neuronal support for instrumental food-acquisition behavior in rabbits with an insulin deficiency].

Behavioural changes during operant learning and feeding were studied in rabbits with insulin deficiency (ID) in chronic ditizone diabetes. Unit activity in the motor and sensorimotor cortex of freely moving rabbits was also studied during the operant behaviour. It was shown that the rabbits with ID displayed much more searching behaviour during learning than the intact ones, although the mean evaluations of the other types of behaviour (grooming, resting, alertness etc.) did not differ significantly. Acceleration of reward learning in the rabbits with ID was also observed. After injection of insulin (2-4 units) an hour before the operant feeding test an extreme reduction of searching behaviour was observed in the rabbits with ID in comparison with the control values as well as an enhancement of grooming, resting and other types of behaviour. Nevertheless, the amount of the operant feeding in this case did not change. Almost a half of neurons (46%) recorded in rabbits with ID manifested prolong activation correlated with the reward and/or food consuming. This proportion of "feeding" neurons in rabbits with ID was much higher than that in control ones (12%). The presented data indicate a significant transformation of behavioural and neuronal patterns in diabetic rabbits during operant reward learning and feeding and allow to consider the enhanced food motivation under ID as the main factor of learning acceleration.

Animals↗
PubMed2000

Vasotocin innervation and modulation of vocal-acoustic circuitry in the teleost Porichthys notatus.

Arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin (AVP) modulate reproduction-related and other social behaviors in a broad range of vertebrate species. These functions of AVT/AVP may be in part achieved through the modulation of sensorimotor integration, although experimental evidence supporting this hypothesis remains limited. In the present experiments, we demonstrate (1) AVT innervation of candidate vocal-acoustic brain regions, and (2) AVT modulation of vocal-motor physiology in the plainfin midshipman fish (Porichthys notatus), which uses vocalizations in both mate attraction and agonistic contexts. AVT distribution was compared with known vocally active brain regions and to central auditory and vocal pathways. AVT-immunoreactive fibers and putative terminals descend almost exclusively from the preoptic area and are found in two primary candidate sites for vocal-acoustic integration - the anterior tuberal hypothalamus and paralemniscal midbrain tegmentum. AVT immunoreactivity is also located in several other vocally active regions, including the ventral tuberal nucleus, periaqueductal gray, and paraventricular regions of the isthmus and rostral hindbrain. The parvocellular preoptic area itself is also vocally active, although thresholds are substantially higher than for other regions. The functional significance of AVT input to vocal-acoustic regions was demonstrated in the paralemniscal midbrain where local delivery of AVT modulated electrically evoked, rhythmic vocal-motor output, which precisely mimicked natural vocalizations. AVT produced dose-dependent inhibitions of parameters associated with call initiation (burst latency and number of vocal-motor bursts elicited) but not of vocal-motor patterning (fundamental frequency and burst duration). Together, these findings provide support for the proposal that AVT modulates sensorimotor processes underlying social/acoustic communication.

Animals↗
PubMed1994

Expression of c-fos mRNA and c-fos protein in neocortical transplants placed into excitotoxin-induced lesions in adult rats.

Using anatomical and electrophysiological methods, previous studies from this laboratory demonstrated that fetal neocortical block transplants placed into the excitotoxically ablated cortex of adult rats can establish functional connections with the host central nervous system. In order to further examine functional integration at the level of genomic activation/molecular signaling systems, transplants were analyzed for the presence of c-fos mRNA and Fos protein-labeled cells following a 20-min exposure of the animal to a novel open-field environment. This behavioral testing paradigm, which previously was shown to induce expression of c-fos mRNA in several brain regions including the sensorimotor cortex, was administered at 3 months after grafting. The transplants were found to express c-fos mRNA as well as c-fos protein following novelty exposure. These labeled cells were distributed primarily along the peripheral margin of the grafts. This study therefore suggests that at least some neurons within transplants become integrated with the host pathways at the level of molecular signal transduction.

Animals↗
PubMed1992

Neuropathological effects of triphenyl phosphite on the central nervous system of the hen (Gallus domesticus).

The neurotoxic effects of single subcutaneous injections of 1000 mg triphenyl phosphite (TPP)/kg body weight were investigated in White Leghorn hens. At 7 days postexposure, birds began to show signs of mild to moderate ataxia that progressed to severe ataxia and paralysis at 21 days. Inhibition of whole brain neuropathy target esterase was 85% at 48 hr and 73% by 21 days postexposure. After postexposure periods of 7, 14, and 21 days, hens were killed and their brains and spinal cords were examined for degenerating axons and terminals using the Fink-Heimer silver impregnation method. A small amount of degeneration was noted at 7 days. By 21 days, dense degeneration was noted in the spinal gray matter and funiculi. Degeneration was also present in the granular cell layer of cerebellar folia I-VI and in nuclei and fiber tracts of the medulla. Moderate to dense degeneration was also seen in several forebrain and midbrain areas including the paleostriatum, ansa lenticularis, the dorso-intermediate thalamic nucleus, lateral spiriform, pedunculopontine tegmental, and lateral mesencephalic nuclei and in the deeper layers of the optic tectum. These results indicate that, in addition to affecting the spinal cord and brainstem, exposure to TPP also damages higher order centers responsible for processing and integrating sensorimotor, visual, and auditory information.

Animals↗