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Target-dependent structural changes accompanying long-term synaptic facilitation in Aplysia neurons.

The mechanisms underlying structural changes that accompany learning and memory have been difficult to investigate in the intact nervous system. In order to make these changes more accessible for experimental analysis, dissociated cell culture and low-light-level video microscopy were used to examine Aplysia sensory neurons in the presence or absence of their target cells. Repeated applications of serotonin, a facilitating transmitter important in behavioral dishabituation and sensitization, produced growth of the sensory neurons that paralleled the long-term enhancement of synaptic strength. This growth required the presence of the postsynaptic motor neuron. Thus, both the structural changes and the synaptic facilitation of Aplysia sensorimotor synapses accompanying long-term behavioral sensitization can be produced in vitro by applying a single facilitating transmitter repeatedly. These structural changes depend on an interaction of the presynaptic neuron with an appropriate postsynaptic target.

Animals↗

Somatotopy and movement representation sites following cortical stroke.

Stroke has been associated with many changes in motor system function, but there has been limited study of changes in somatotopic organization. This was examined in a group of patients with cortical stroke affecting primary sensorimotor cortex. In 17 patients with good outcome after cortical stroke involving precentral and/or postcentral gyri, plus 14 controls, four functional MRI evaluations of brain activity were obtained: finger, shoulder, and face motor tasks plus a sensory task, passive finger motion. For each, coordinates for contralateral primary sensorimotor cortex activation site were determined, as was a measure of inter-hemispheric balance. The normal motor somatotopy measured in controls was largely preserved after stroke. The main difference found between controls and patients was that the face was lateral to finger motor activation in all controls, but face was centered medial to finger in 43% of patients. Among patients, smaller infarct volume was associated with more ventral, and larger infarct with more dorsal, contralateral primary sensorimotor cortex activation. On the other hand, better behavioral outcome was associated with a more posterior, and poorer outcome with more anterior, activation. Larger infarct and poorer behavioral outcome were each associated with a change in inter-hemispheric balance towards the non-stroke hemisphere. Shifts in contralateral movement representation site did not correlate with changes in inter-hemispheric balance. Motor somatotopy is generally preserved after injury to primary sensorimotor cortex. Greater injury and larger behavioral deficits are associated with distinct effects on movement representation sites. Changes in motor organization within and between hemispheres arise independently after stroke.

Adult↗

Effects of MK-801 on recovery from sensorimotor cortex lesions.

Histologic evidence suggests that drugs acting as noncompetitive antagonists at the N-methyl-D-aspartate receptor can have beneficial or pathologic effects on central nervous system neurons. In the present experiments we examined the effects of MK-801 on recovery of behavioral function after unilateral lesions in the rat somatic sensorimotor cortex. In the first experiment, rats with unilateral sensorimotor cortex lesions were given either MK-801 (1 mg/kg) or saline 12-16 hours after surgery. Additional injections were given on postoperative days 2, 4, and 6. Behavioral tests measured somatosensory asymmetries (i.e., bilateral tactile stimulation tests) and forelimb placing. After creation of sensorimotor cortex lesions, rats showed an ipsilateral somatosensory bias and an impairment in placing the contralateral forelimb. Rats treated with MK-801 recovered slightly faster than saline-treated animals as measured by a bilateral tactile stimulation test (p less than 0.05). In contrast, there was no significant difference between the groups in the recovery of forelimb placing. In a second experiment, rats with sensorimotor cortex lesions were treated with a single injection of MK-801 after behavioral recovery. Twenty hours after the MK-801 injection, rats with sensorimotor cortex lesions showed a reinstatement of the placing deficits. The impairment endured for at least 7 days after injection. These behavioral data support the idea that MK-801 can have either beneficial or detrimental effects when administered after brain damage.

Animals↗

Functional reconfiguration of midbrain neurons by ovarian steroids in behaving hamsters.

Previous studies have demonstrated the importance of the midbrain, especially the tectum, in the sensorimotor control of the sexually-receptive posture, lordosis, in female golden hamsters. In the present study, midbrain single unit activity was recorded during hormonal induction of lordosis, to identify neuronal activity mediating the sensorimotor control of the response and to observe functional changes in these neurons associated with the hormones' behavioral effect. Progesterone administration to estrogen-primed hamsters initiated pronounced changes in neuronal activity levels, somatosensory responsiveness and movement-related firing. These changes began in some neurons within 10 min of subcutaneous hormone injection and affected progressively more neurons until lordosis was elicitable 2-4 hr later. The pattern of these changes, including increased neuronal responsiveness to lumbosacral stimuli, appearance of lordosis-related firing (especially in the tectum) and reduced incidence of firing associated with lordosis-incompatible behaviors, constituted a transformation, or reconfiguration of midbrain sensorimotor function. It is proposed that this reconfiguration enables the elicitation and maintenance of lordosis by lumbosacral stimuli. Neural effects of comparable magnitude didn't result from control progesterone injections which failed to induce lordosis.

Animals↗

Iloperidone reduces sensorimotor gating deficits in pharmacological models, but not a developmental model, of disrupted prepulse inhibition in rats.

Iloperidone is a novel atypical antipsychotic which acts as a broad spectrum dopamine/serotonin/norepinephrine receptor antagonist. To compare iloperidone behaviorally to other known antipsychotics, we evaluated the drug in three pharmacological models and one developmental model of disrupted prepulse inhibition (PPI) in rats. Firstly, 0.5 mg/kg apomorphine induced PPI deficits that were prevented by pretreatment with iloperidone (1 and 3 mg/kg). Secondly, treatment with the N-methyl-D-aspartate (NMDA)-receptor antagonist phencyclidine (PCP) produced robust deficits in PPI. Both doses of iloperidone (1 and 3 mg/kg) prevented the PPI-disruptive effects of treatment with 1 mg/kg PCP. Thirdly, treatment with the alpha1-adrenoceptor agonist cirazoline (0.6 mg/kg) disrupted PPI, and produced a concurrent large increase in startle magnitude. A relatively low dose of iloperidone (0.3 mg/kg) prevented cirazoline-induced PPI deficits, independent of its effects on startle magnitude. Finally, iloperidone (1 mg/kg) did not reverse PPI deficits in the isolation-rearing model of schizophrenia. These results indicate that iloperidone exerts behavioral effects in pharmacological models of disrupted sensorimotor gating consistent with "atypical" antipsychotics, mediated by antagonism of dopaminergic and noradrenergic receptors. The absence of effect in isolation-reared rats may be due to the relatively small effect size of isolation rearing on PPI or dose of iloperidone.

Acoustic Stimulation↗

Behavioral recovery and anatomical plasticity in adult rats after cortical lesion and treatment with monoclonal antibody IN-1.

We have previously reported that monoclonal antibody (mAb) IN-1 treatment after ischemic infarct in adult rats results in significant recovery of skilled forelimb use. Such recovery was correlated with axonal outgrowth from the intact, opposite motor cortex into deafferented subcortical motor areas. In the present study, we investigated the effects of mAb IN-1 treatment after adult sensorimotor cortex (SMC) aspiration lesion on behavioral recovery and neuroanatomical plasticity in the corticospinal tract. Adult rats underwent unilateral SMC aspiration lesion and treatment with either mAb IN-1 or a control Ab, or no treatment. Animals were then tested over a 6-week period in the skilled forelimb use task and the skilled ladder rung walking task. We found that animals treated with mAb IN-1 after SMC lesion fully recovered the use of forelimb reaching, but showed no improvement in digit grasping as tested in the skilled forelimb use task. The mAb IN-1 treatment group was also significantly improved as compared to control groups in the skilled ladder rung walking test. Furthermore, neuroanatomical tracing revealed a significant increase in the corticospinal projections into the deafferented motor areas of the spinal cord after mAb IN-1 treatment. These results indicate that treatment with mAb IN-1 after cortical aspiration lesion induces remodeling of motor pathways resulting in recovery in only certain behavioral tasks, suggesting that the cause of brain damage influences behavioral recovery after mAb IN-1 treatment.

Analysis of Variance↗

Interpolation and extrapolation in human behavior and neural networks.

Unlike most artificial systems, the brain is able to face situations that it has not learned or even encountered before. This ability is not in general echoed by the properties of most neural networks. Here, we show that neural computation based on least-square error learning between populations of intensity-coded neurons can explain interpolation and extrapolation capacities of the nervous system in sensorimotor and cognitive tasks. We present simulations for function learning experiments, auditory-visual behavior, and visuomotor transformations. The results suggest that induction in human behavior, be it sensorimotor or cognitive, could arise from a common neural associative mechanism.

Adaptation, Psychological↗

Visuomotor restriction of one eye in kittens reared with alternate monocular deprivation.

It is known that kittens reared in ways that restrict movement while visual stimulation is received exhibit deficits in visually guided behavior. Presumably, the behavioral dysfunction is due to a lack of sensorimotor coordination during visual exposure. The current investigation was undertaken to study this effect both physiologically and behaviorally. Two groups of kittens were normally reared until they were nearly 4 weeks old. They were then placed in a darkroom and exposed daily for 1--2 hours while one eye was occluded. On alternate days, alternate eyes were covered. One group was restrained in a body cast while a given eye was exposed, but the kittens were free to move about while the other eye received visual experience. A second control group was alternately occluded, but freely mobile during all exposures. An additional cat was also unrestrained during daily rearing periods and neither eye was ever occluded. Behavioral tests showed clear deficits when the "passive" eye of the restrained-unrestrained group was used. Deficiencies were found in visually guided paw placing, pursuit eye movements, and jumping behavior to a platform. Responses of single cells were studied in area 17 of the visual cortex. Ocular dominance distributions showed marked reductions in binocularity for alternated occluder cats. The eye that had received exposure while animals were active in the restrained-unrestrained group also tended to predominate but the difference was not statistically significant.

Animals↗

A genetic screen for novel behavioral mutations in mice.

A genetic screen using mice was performed to identify dominant loci affecting behavior. Mice were mutagenized with ENU, then bred to examine their G1 offspring for behavioral abnormalities. Potentially mutant G1 pups were screened through a variety of behavioral assays, including tests of learning and memory, sensorimotor gating, fear and anxiety, nociception (pain perception) and locomotor activity. Mice falling outside the normal performance distribution in these tests were considered potential behavioral mutants and were bred for further analysis. Outliers included both animals with very discrete defects and animals with abnormal performance across a range of tests. To date, we have identified two confirmed mutants affecting sensorimotor gating. These results provide further impetus for the use of random mutagenesis screens as a tool for dissecting the genetic basis of brain and behavior.

Alkylating Agents↗

Peripheral motor dynamics of song production in the zebra finch.

Singing behavior in songbirds is a model system for motor control of learned behavior. The target organs of its central motor programs are the various muscle systems involved in sound generation. Investigation of these peripheral motor mechanisms of song production is the first step toward an understanding of how different motor systems are coordinated. Here we review physiological studies of all major motor systems that are involved in song production and modification in the zebra finch (Taeniopygia guttata). Acoustic syllables of zebra finch song are produced by a characteristic air sac pressure pattern. Electromyographic (EMG) and sonomicrometric recording of expiratory muscle activity reveals that respiratory motor control is tightly coordinated with syringeal gating of airflow. Recordings of bronchial airflow demonstrate that most of the song syllables are composed of simultaneous independent contributions from the two sides of the syrinx. Sounds generated in the syrinx can be modified by the resonance properties of the upper vocal tract. Tracheal length affects resonance, but dynamic changes of tracheal length are unlikely to make a substantial contribution to sound modification. However, beak movements during song contribute to sound modification and, possibly, affect the vibratory behavior of the labia. Rapid beak aperture changes were associated with nonlinear transitions in the acoustic structure of individual syllables. The synergy between respiratory and syringeal motor systems, and the unique bilateral, simultaneous, and independent sound production, combined with dynamic modification of the acoustic structure of song, make the zebra finch an excellent model system for exploring mechanisms of sensorimotor integration underlying a complex learned behavior.

Animals↗

The influence of bufotenin on the feeding behavior and cerebral serotonin content in rats.

By researches carried out in male adult rats (Wistar), the influence of the intraperitoneally injected bufotenin (5 mg/kg b.w. active substance in saline solution) was followed on: I--feeding behavior; II--the serotonin concentration in hypothalamus, rhinencephalon, mesencephalon and sensorimotor cerebral cortex. The obtained results show that bufotenin influences the feeding behavior by reducing the motor functions. Its action depends on the physiological state of the animal: by increasing the alimentary motivation the rats can escape the bufotenin influence, showing a normal behavior; bufotenin does not influence the sensorials, the natural dispositions and the excitability level of the feeding and satiety hypothalamic centers. Bufotenin increases serotonin concentration only in the mesencephalic region, but not in the other studied regions. The results are interpreted as a primary bufotenin action on the serotoninic vasoconstrictive receptors at the mesencephalic level, thus disturbing the serotonin-releasing processes and possibly other chemical neurotransmitters.

Animals↗

Mesolimbicocortical dopamine terminal fields are necessary for normal locomotor and investigatory exploration in rats.

Rats explore a novel open field or novel object less after denervation of mesolimbicocortical dopaminergic terminal fields produced by bilateral 6-hydroxydopamine (6-OHDA) microinjections into the anterolateral hypothalamus after pretreatment with desmethylimipramine (DMI). These behavioral deficits were correlated with complete or nearly complete loss of fluorescent dopaminergic (DA) terminals in the nucleus accumbens, olfactory tubercle, dorsal bed nucleus of the stria terminalis, lateral septal nucleus and the deep layers of the frontal and piriform cortices. There were also fewer A10, medial A9, and A8 DA fluorescent cells after the 6-OHDA-DMI injections; this suggests retrograde degeneration of the cells of origin of the mesolimbicocortical DA system. When the DMI pretreatment was omitted, identical bilateral 6-OHDA microinjections also produced severe loss of norepinephrine (NE) fibers in the neocortex, hippocampus, lateral hypothalamus and ventral bed nucleus of the stria terminalis. The addition of this noradrenergic damage did not change the exploratory deficits observed after mesolimbicocortical DA denervation alone. Systemic administration of the DA agonist apomorphine, but not the adrenergic agonist clonidine, to the 6-OHDA-DMI rats repaired the deficits in exploration of a novel open field or novel object. The increased locomotion in a novel open field and investigation of a novel object produced by apomorphine in 6-OHDA-DMI rats were blocked by the DA antagonist, pimozide. This is evidence that apomorphine restored exploratory responses by stimulating dopaminergic receptors. The exploratory responses produced by apomorphine were also blocked by testing rats in a familiar open field or with a familiar novel object. This is evidence that apomorphine facilitates exploratory responding to novel stimuli by 6-OHDA-DMI rats, but that the same dose of apomorphine does not increase activity when 6-OHDA-DMI rats are confronted by familiar stimuli. We conclude: (1) that mesolimbicocortical dopaminergic terminals are necessary for normal exploratory behavior in rats; and (2) that DA released by these terminals may facilitate optimal sensorimotor integration in these terminal fields during spontaneous exploratory behavior.

Animals↗

Role of dopamine in the primate caudate nucleus in reward modulation of saccades.

Expected reward impacts behavior and neuronal activity in brain areas involved in sensorimotor processes. However, where and how reward signals affect sensorimotor signals is unclear. Here, we show evidence that reward-dependent modulation of behavior depends on normal dopamine transmission in the striatum. Monkeys performed a visually guided saccade task in which expected reward gain was different depending on the position of the target. Saccadic reaction times were reliably shorter on large-reward trials than on small-reward trials. When position-reward contingency was switched, the reaction time difference changed rapidly. Injecting dopamine D1 antagonist into the caudate significantly attenuated the reward-dependent saccadic reaction time changes. Conversely, injecting D2 antagonist into the same region enhanced the reward-dependent changes. These results suggest that reward-dependent changes in saccadic eye movements depend partly on dopaminergic modulation of neuronal activity in the caudate nucleus.

Animals↗

Alterations in intracerebral hemorrhage-induced brain injury in the iron deficient rat.

BACKGROUND: Iron contributes to brain edema and cellular toxicity after intracerebral hemorrhage (ICH). Knowledge regarding ICH in the context of iron deficiency anemia (IDA), a common nutritional disorder, is limited. OBJECTIVE: To determine the effect of IDA on brain and behavioral outcome after ICH in rats. METHODS: Six-week-old male rats (n = 75) were randomized to non-IDA or IDA groups. After 1 month of iron sufficient or deficient diets, 100 microl autologous blood was infused into the right basal ganglia (BG). Brains were assessed for iron concentration, regional water content, BG transferrin, and transferrin receptor concentrations after ICH. Recovery of upper extremity sensorimotor function was assessed. Brain and behavioral variables were compared by diet group. Significance was set at p < 0.05. RESULTS: Whole brain iron was decreased and water content was increased for IDA rats in injured cortex and BG at day 3 (p < 0.05) compared with non-IDA rats. Transferrin and transferrin receptor content were increased in injured BG for IDA compared to non-IDA in the first week after ICH (p < 0.05). IDA rats had greater left vibrissae-stimulated forelimb-placing deficits and forelimb-use asymmetry than non-IDA after ICH (p < 0.05). CONCLUSIONS: Brain iron status may be an important determinant of injury severity and recovery after ICH.

Anemia, Iron-Deficiency↗

[Nle4,D-Phe7]alpha-MSH improves functional recovery in rats subjected to diencephalic hemisection.

Rats subjected to diencephalic hemisection were s.c. treated with alpha-MSH (20 micrograms/rat daily) or with [Nle4,D-Phe7]alpha-MSH (10 micrograms/rat every other day) for two weeks starting on day 3 after lesion. Apomorphine-induced (1 mg/kg s.c.) rotational behavior was studied on days 7, 14 and 21 after lesion, and a sensorimotor test battery was carried out on days 3, 10, 17 and 24 after lesion. [Nle4,D-Phe7]alpha-MSH greatly reduced rotational behavior and significantly improved sensorimotor performance. Histological studies showed that treatment with alpha-MSH and, even more markedly, with [Nle4,D-Phe7]alpha-MSH reduced the size of the lesion and the pseudoinflammatory reaction, and caused a marked proliferation and hypertrophy of astroglia. Binding studies showed that no supersensitivity of striatal dopamine receptors developed on the lesioned side of alpha-MSH- and [Nle4,D-Phe7]alpha-MSH-treated rats. The present results seem to further support the trophic role of MSH peptides on nerve tissue.

Animals↗

The neuronal basis of feeding in the snail, Helisoma, with comparisons to selected gastropods.

Research on identified neurons during the last quarter century was forecast at a conference in 1973 that discussed "neuronal mechanisms of coordination in simple systems." The focus of the conference was on the neuronal control of simple stereotyped behavioral acts. Participants discussing the future of such research called for a comparative approach; emphasis on structure-function interactions; attention to environmental and behavioral context; and the development of new techniques. Significantly, in some cases amazing progress has been made in these areas. Major conclusions of the last quarter century are that so-called simple behaviors and the neural circuitry underlying them tend to be less simple, more flexible, and more highly modulated than originally imagined. However, the comparative approach has, as yet, failed to reach its potential. Molluscan preparations, along with arthropods and annelids, have always been at the forefront of neuroethological studies. Circuitry underlying feeding has been studied in a handful of species of gastropod molluscs. These studies have contributed substantially to our understanding of sensorimotor organization, the hierarchical control of behavior and coordination of multiple behaviors, and the organization and modulation of central pattern generators. However, direct interspecific comparisons of feeding circuitry and potentially homologous neurons have been lacking. This is unfortunate because much of the vast radiation of the class Gastropoda is associated with variations in feeding behaviors and feeding apparatuses, providing ample substrates for comparative studies including the evolution of defined circuitry. Here, the neural organization of feeding in the snail, Helisoma, is examined critically. Possible direct interspecific comparisons of neural circuitry and potentially homologous neurons are made. A universal model for central pattern generators underlying rasping feeding is proposed. Future comparative studies can be expected to combine behavioral, morphological, electrophysiological, molecular and genetic techniques to identify neurons and define neural circuitry. Digital resources will undoubtedly be exploited to organize and interface databases allowing illumination of the evolution of homologous identified neurons and defined neural circuitry in the context of behavioral change.

Action Potentials↗

Local fluorouracil chemotherapy interferes with neural and behavioral recovery after brain tumor-like mass compression.

In this study, we investigated the impact of intracerebral delivery of chemotherapy on functional recovery from focal cortical tissue displacement, characteristic of brain tumors. Unilateral focal brain compression was induced by epidural implantation of an inverted hemisphere-shaped bead over the sensorimotor cortex. Microinjections of a total of 1mg chemoagent fluorouracil or the same volume of saline were made into the compressed cortex. Behavioral tests of forelimb sensorimotor function were conducted during 4 weeks' observation. Rats subjected to any of the three types of lesions, saline microinjection plus cortical compression, chemoagent microinjection alone, or chemoagent microinjection combined with cortical compression, demonstrated significant behavioral deficits in several sensorimotor tasks, compared with saline-microinjected control animals. In placing tests, behavioral deficits elicited by each single treatment were worsened by combined treatment with chemoagent microinjection and focal cortical compression. Concurrently, local delivery of chemoagent into the compressed cortex induced increased cortical tissue loss, necrosis and apoptosis. These data indicate that local chemotherapy exacerbates compression-induced neurological impairment, and a model of controlled focal cortical compression may provide a valuable means to improve anti-cancer therapeutic designs with reduced deterioration of brain function.

Animals↗

Sensorimotor treatment of chronic schizophrenics.

A pilot study, a sensorimotor treatment program, was conducted that involved five subjects. The subjects ranged in age from 23 to 49 and all carried a diagnosis of schizophrenia. Length of hospitalization ranged from 3 years to 30 years with only brief interruptions. Patients were evaluated before treatment, after six weeks of treatment, and six weeks after termination of treatment. Evaluation procedures used were: DRAW-A-PERSON Test; NOSIE; Posture Evaluation; and the Step Test. Results showed a decrease in overt psychotic behavior that did not last after sensorimotor treatment was discontinued; improved posture and gait in most patients; and improved body concept. There were no significant changes in pulse, blood pressure, or respiration rates.

Body Image↗