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Specificity of sensorimotor learning and the neural code: neuronal representations in the primary motor cortex.

Human studies show that the learning of a new sensorimotor mapping that requires adaptation to directional errors is local and generalizes poorly to untrained directions. We trained monkeys to learn new visuomotor rotations for only one target in space and recorded neuronal activity in the primary motor cortex before, during and after learning. Similar to humans, the monkeys showed poor transfer of learning to other directions, as observed by behavioral aftereffects for untrained directions. To test for internal representations underlying these changes, we compared two features of neuronal activity before and after learning: changes in firing rates and changes in information content. Specific elevations of firing rate were only observed in a subpopulation of cells in the motor cortex with directional properties corresponding to the locally learned rotation; namely cells only showed plasticity if their preferred direction was near the training one. We applied measures from information theory to probe for learning-related changes in the neuronal code. Single cells conveyed more information about the direction of movement and this specific improvement in encoding was correlated with an increase in the slope of the neurons' tuning curve. Further, the improved information after learning enabled a more accurate reconstruction of movement direction from neuronal populations. Our findings suggest a neural mechanism for the confined generalization of a newly acquired internal model by showing a tight relationship between the locality of learning and the properties of neurons. They also provide direct evidence for improvement in the neural code as a result of learning.

Action Potentials↗

Preference for symmetry is experience dependent in newborn chicks (Gallus gallus).

Spontaneous pecking preferences toward symmetric or asymmetric stimuli were tested in newborn chicks (Gallus gallus). A preference for asymmetric patterns was found in naïve chicks (either 24 or 48 hours old), although a preference for symmetry appeared at retest after chicks had experienced standard rearing conditions (Experiments 1 and 2). Only food-experienced chicks preferred symmetric patterns; food-deprived and hand-fed chicks did not show any preference (Experiment 3). A key factor that allowed for the emergence of a preference for symmetry may relate to the improving of pecking sensorimotor skills occurring during active food manipulation. Possible explanations are discussed for the late emergence of the preference for symmetry and for the preference for asymmetry found in naïve chicks.

Age Factors↗

Neural mechanisms of birdsong memory.

The process through which young male songbirds learn the characteristics of the songs of an adult male of their own species has strong similarities with speech acquisition in human infants. Both involve two phases: a period of auditory memorization followed by a period during which the individual develops its own vocalizations. The avian 'song system', a network of brain nuclei, is the probable neural substrate for the second phase of sensorimotor learning. By contrast, the neural representation of song memory acquired in the first phase is localized outside the song system, in different regions of the avian equivalent of the human auditory association cortex.

Animals↗

Rationale for a model of human systems integration: the need of a theoretical framework.

Human systems integration (HSI) involves augmented human design with the objectives of augmenting human capabilities and improving human performance using behavioral technologies. The fundamental matter of human systems integration and augmented human design is the organization and the nature of interactions that couple physiological systems, humans- and engineered systems, artifacts. By this definition, augmented human consists of interactive artefacts linked to physiological systems. This paper focuses on the rationale of a HSI model based on specific experiments (comparison of dynamical sensorimotor integration and motor performances in real and virtual environments) that confirm the hypothesis of functional interaction in the framework of Chauvet's mathematical theory of integrative physiology (MTIP). Epistemological constraints for HSI and the role of MTIP are briefly discussed in this context.

Adult↗

A choice reaction-time task in the rat: a new model using air-puff stimuli and lever-release responses.

We have developed a two-lever choice reaction-time (RT) task to investigate the behavioral and neural mechanisms of stimulus-response compatibility in rats. In the task, the rat pressed two levers with its forepaws during the preparation period of each trial, and then quickly responded to an air-puff stimulus on its left or right forepaw by releasing the lever on the same side (compatible condition) or the opposite side (incompatible condition) of the stimulus. Twenty rats successfully learned the task in both the compatible and incompatible conditions. Two stimulus-response compatibility effects were observed: the RT was shorter and the error rate was lower in the compatible condition than in the incompatible condition. The trial sequence also affected the results and a speed-accuracy tradeoff was observed. These results are consistent with those reported for human RT tasks. Furthermore, a lesion in the forepaw-sensorimotor cortex caused increases in the RTs for stimulus detection and/or response movement with the contralateral forepaw, suggesting that the task was mediated by this brain area. We conclude that this instrumental task for rats can be regarded as a model for human RT tasks and can be used to investigate the neural basis of the compatibility effects.

Air↗

Multi-chemical networking profile of the living human brain: potential relevance to molecular studies of cognition and behavior in normal and diseased brain.

Anatomical, electrophysiological and functional neuroimaging studies show that the human brain is a complex network, where cortico-cortical and thalamo-cortical connections are organized in a specific pattern giving rise to brain function. In our recent studies we found that chemical connectivity between brain regions might be changed in different conditions (e.g. aging, chronic pain, cognitive interference). The elucidation of properties of the human brain multi-chemical networking profile is the subject of this study. In vivo proton magnetic resonance spectroscopy was used to determine relative concentrations of multiple chemicals (N-Acetyl aspartate, choline, glutamate, glutamine, GABA, inositol, glucose, and lactate in relation to creatine/phosphocreatine complex) in 6 brain regions: thalamus, and cingulate, insula, sensorimotor, orbital frontal, and dorsolateral prefrontal cortices. The properties of the brain multi-chemical networking profile within and across the studied regions were examined using correlation analysis. Strong positive correlations were seen between chemicals within brain regions. Negative correlations were primarily seen across brain regions. The cortical connectivity for both neurotransmitters (GABA and glutamate) was stronger than for the other chemicals, and was stronger than for the same neurotransmitters in the thalamus. Factor analysis indicated that the natural clustering of regional chemical concentrations is by brain region and not by chemicals. These findings support the idea for the existence of a specific pattern of multi-chemical networking profile in the brain where the major excitatory and inhibitory neurotransmitters in neocortex perform a regulatory function.

Adult↗

Limits on reacquisition of song in adult zebra finches exposed to white noise.

Zebra finches (Taeniopygia guttata) learn a specific song pattern during a sensitive period of development, after which song changes little or not at all. However, recent studies have demonstrated substantial behavioral plasticity in song behavior during adulthood under a range of conditions. The current experiment examined song behavior of adult zebra finches temporarily deprived of auditory feedback by chronic exposure to loud white noise (WN). Long-term exposure to continuous WN resulted in disruption of song similar to that observed after deafening. When auditory feedback was restored by discontinuing WN, birds were either tutored using tape-recorded playback or housed with adult conspecific tutors. No evidence of learning new tutor syllables was observed, and recovery of pre-WN song patterns was very limited after restoration of hearing. However, many birds did reacquire some aspects of their pretreatment song, suggesting an adult form of learning that may retain some of the initial aspects of sensorimotor acquisition of song in which vocalizations are shaped to match a stored template representation. The failure to learn novel song elements and the modest degree of recovery observed overall suggest a limit on plasticity in adult birds that have acquired species-typical song patterns and may reflect an important species difference between zebra finches and Bengalese finches.

Age Factors↗

The induction and modification of voltage-sensitive responses in cat neocortical neurons by N-methyl-D-aspartate.

The actions of the excitatory amino acid, N-methyl-D-aspartate (NMDA), on layer V neurons of cat sensorimotor cortex were examined in an in vitro slice preparation using current clamp, single electrode voltage clamp (SEVC), and ionic substitution techniques. Low doses of NMDA evoked a slow depolarization with a net decrease of input conductance. Larger doses additionally evoked repetitive firing, rhythmic depolarization shifts (DSs), low-threshold calcium spikes (in the presence of TEA+) and bistable membrane potential behavior. Ionic substitution experiments suggested that entry of both Ca2+ and Na+ ions contributed to the NMDA responses. Attention was focused on the NMDA response with Ca2+ entry blocked. Examination by SEVC revealed that, in both normal cells and in the presence of several blocking agents, NMDA induced a highly voltage-dependent inward ionic current which could result in a region of negative slope conductance on the cell's current-voltage relation. The development of this current seems capable of accounting for all aspects of the observed response, including the DSs and low-threshold Ca2+ spikes. Substitution of TEA+ for most external Na+ (with Ca2+ entry blocked) largely eliminated the NMDA responses and corresponding ionic current. Our results in neocortical neurons are compared to those recently obtained in cultured murine neurons.

Animals↗

Frontal cortex stimulation evoked neostriatal potentials in rats: intracellular and extracellular analysis.

Evoked potentials, action potentials and intracellular events were recorded in the neostriatum of urethane anesthetized rats to electrical stimulation of frontal cortex white matter, motor cortex and pre-limbic cortex. Five major waves of the evoked potential were identified. Wave N1 (3.9 msec latency) was small, preceded cellular events and probably represents activation of corticostriate terminals. Wave P1 (10.8 msec latency to peak following white matter stimulation) coincided with an EPSP and neuronal firing. Both wave N2 (38.0 msec latency to peak) and P2 (approximately 110 msec duration) overlapped the intracellularly recorded hyperpolarization and inhibition of cell firing. Based upon this correspondence and upon the behavior of waves N2 and P2 with changing current and during conditioning-test paired pulse stimulation, it was concluded that the waves represent different processes contributing to the cellular hyperpolarization. A late wave, N3 (175 msec onset latency) corresponded to a late rebound firing and cellular depolarization. This late wave was eliminated from the neostriatum, but not from the overlying sensorimotor cortex, by kainic acid lesions that destroyed medial thalamus but left thalamic lateral nuclei and reticular nucleus intact.

Animals↗

Integration of posture and movement: contributions of Sherrington, Hess, and Bernstein.

Neural mechanisms that integrate posture with movement are widespread throughout the central nervous system (CNS), and they are recruited in patterns that are both task- and context-dependent. Scientists from several countries who were born in the 19th century provided essential groundwork for these modern-day concepts. Here, the focus is on three of this group with each selected for a somewhat different reason. Charles Sherrington (1857-1952) had innumerable contributions that were certainly needed in the subsequent study of posture and movement: inhibition as an active coordinative mechanism, the functional anatomy of spinal cord-muscle connectivity, and helping set the stage for modern work on the sensorimotor cortex and the corticospinal tract. Sadly, however, by not championing the work of his trainee and collaborator, Thomas Graham Brown (1882-1965), he delayed progress on two key motor control mechanisms: central programming and pattern generation. Walter Hess (1881-1973), a self-taught experimentalist, is now best known for his work on CNS coordination of autonomic (visceral) and emotional behavior. His contributions to posture and movement, however, were also far-reaching: the coordination of eye movements and integration of goal-directed and "framework" (anticipatory set) motor behavior. Nikolai Bernstein (1896-1966), the quintessence of an interdisciplinary, self-taught movement neuroscientist, made far-reaching contributions that were barely recognized by Western workers prior to the 1960s. Today, he is widely praised for showing that the CNS's hierarchy of control mechanisms for posture and movement is organized hand-in-hand with distributed and parallel processing, with all three subject to evolutionary pressures. He also made important observations, like those of several previous workers, on the goal focus of voluntary movements. The contributions of Sherrington, Hess, and Bernstein are enduring. They prompt thought on the philosophical axioms that appear to have driven their research, and the continual need for emphasis on interdisciplinary, comparative, and transnational approaches to advance movement neuroscience.

Affect↗

Denervation and repeated L-DOPA induce complex regulatory changes in neurochemical phenotypes of striatal neurons: implication of a dopamine D1-dependent mechanism.

Motor complications induced through repeated L-DOPA treatment in patients with Parkinson's disease are thought to be the consequence of molecular adaptations that occur in response to repeated dopamine receptors stimulation. Here, we studied the molecular changes taking place in the denervated striatum of unilaterally 6-OHDA-lesioned rats repeatedly treated with L-DOPA alone or combined to the D1 receptor antagonist SCH23390. We looked at the territorial patterns of expression of neurotensin (NT), dynorphin (DYN), enkephalin (ENK) and Nur77 (also known as NGFI-B) mRNA expression in the striatum and contrasted these with markers of glutamatergic transport and dopaminergic receptor functions. The denervation process induced NT and Nur77 mRNA expression in ENK-positive cells. Subsequent repeated L-DOPA treatment led to a sensitization of L-DOPA-induced rotational response and produced a second surge of NT induction, this time limited to DYN-positive cells and preferentially restricted to the lateral striatum. In this specific territory, the number of Nur77-positive cells was decreased, in response to L-DOPA, when compared to the medial part of the lesioned striatum. L-DOPA treatment increased dopamine D3 receptor and glutamate transporter 1 (GLT1) mRNA expression in the lesioned striatum and that, specifically in an area overlapping one of Nur77 decrease and of NT/DYN induction. The concomitant administration of SCH23390 with repeated L-DOPA treatment blocked the development of behavioral sensitization and the appearance of all L-DOPA-induced molecular reorganizations reported above. Our results showed that repeated L-DOPA treatment produces, in a denervated striatum, a complex pattern of genes regulation in both the direct and the indirect striatal output pathways. This phenomenon is located preferentially in a striatal area receiving converging inputs from the thalamus and sensorimotor cortex and is dependent upon D1 receptor stimulation.

Animals↗

Internal forward models in the cerebellum: fMRI study on grip force and load force coupling.

Internal models are neural mechanisms that can mimic the input-output or output-input properties of the motor apparatus and external objects. Forward internal models predict sensory consequences from efference copies of motor commands. There is growing acceptance of the idea that forward models are important in sensorimotor integration as well as in higher cognitive function, but their anatomical loci and neural mechanisms are still largely unknown. Some of the most convincing evidence that the central nervous system (CNS) makes use of forward models in sensory motor control comes from studies on grip force-load force coupling. We first present a brief review of recent computational and behavioral studies that provide decisive evidence for the utilization of forward models in grip force-load force coupling tasks. Then, we used functional magnetic resonance imaging (fMRI) to measure the brain activity related to this coupling and demonstrate that the cerebellum is the most likely site for forward models to be stored.

Adult↗

Early iron deficiency alters sensorimotor development and brain monoamines in rats.

Iron deficiency in human infancy reportedly leads to developmental delays and changes in neurobiology that may be irreversible. Using a rodent model, the present study examined whether dietary iron deficiency late in pregnancy and during lactation alters sensorimotor development and brain monoaminergic systems. Rats were assigned to 1 of 4 dietary treatments during gestation and lactation: 1) iron sufficient control; 2) prenatal iron deficiency beginning on gestational d 15 (G15); 3) postnatal iron deficiency beginning on postnatal d 4 (P4); 4) iron deficiency beginning on G15 followed by an iron sufficient diet on P4. Developmental milestones, open field behavior, brain iron and proteins, monoamines, and their transporters were evaluated between P6 and P21. Only G15 iron deficient rats had greater dopaminergic activity than controls as indicated by increased tyrosine hydroxylase levels, phosphorylated tyrosine hydroxylase levels, and cellular dopamine in prefrontal cortex and striatum at P15. These rats also showed delayed eye opening, ear development, and reduced locomotor activity. Iron repletion at P4 returned most measures to control levels by the time of weaning. Postnatal iron deficiency reduced striatal and ventral midbrain iron as well as cellular dopamine levels in prefrontal cortex and striatum at P21. Developmental delays in ear development and achievement in bar holding and surface righting also resulted from postnatal iron deficiency. These results indicate that iron deficiency begun at G15 affects early dopamine neurobiology, the development of specific developmental milestones, and behavior in preweaned rats.

Aging↗

Evaluation of a motor deficit after chronic focal cerebral ischemia in rats.

It is well known that hemiplegia is frequently observed in cerebral ischemia. It is important for the pathophysiologic study and development of drug therapies to establish a precise method investigating impairment of motor function with animal models. To develop a quantitative and objective method for evaluating impairment of motor function, we examined an inclined plane test after chronic focal cerebral ischemia in the rat. Standard scoring of neurologic deficits has limitations, including problems with quantification and objectivity. The purpose of this study was to establish a novel method for evaluating impairment of motor function in middle cerebral artery (MCA) occluded rats. The left MCA was permanently occluded at a proximal site, and sensorimotor performance was evaluated at the fifth day and every week for 11 weeks thereafter. The ability to maintain body position on an inclined plane was measured when rats were placed on a stainless steel slope in left-headed, right-headed, and up-headed positions. Neurologic examination based on hemiparesis and abnormal posture was also performed. After all behavioral examinations were completed, the degree of shrinkage of the left hemisphere to the contralateral was measured. The ability of MCA-occluded rats to maintain position on an inclined plane in the left-headed position was significantly restricted when compared with that of sham-operated rats throughout the test period (maximum angle of 37 degrees versus 45 degrees, respectively). Minimal natural recovery was observed for all position measurements. MCA-occluded rats showed a significantly higher neurologic score with natural recovery. The ability to maintain position on an inclined plane after MCA occlusion (MCAO) was significantly correlated with the degree of the shrinkage of the ischemic hemisphere and neurologic score. The angle for the left-headed position was most strongly correlated with ipsilateral shrinkage. In the present study, long-lasting impairment of motor function was detected in rats with MCAO, which correlated with the shrinkage of the ischemic hemisphere. Furthermore, a difference in performance depending on body position (left-headed versus right-headed) was also detected. The left-headed position was found to be most sensitive for evaluating this model. The inclined plane test is a quantitative, objective, and sensitive method for evaluating motor deficits after chronic focal cerebral ischemia in rats, and this method may be useful to investigate changes in motor function in hemiplegia.

Animals↗

Functional observational battery comparing effects of ethanol, 1,1,1-trichloroethane, ether, and flurothyl.

Several recent reports have demonstrated that acute solvent exposure in animals produces a profile of neurobehavioral effects similar to that of classical CNS depressant drugs such as the barbiturates and ethanol. The present investigation further delineated the behavioral pharmacology of three solvents [1,1,1-trichloroethane (TCE), ether, and flurothyl] using a functional observational battery (FOB) composed of 21 qualitative and quantitative measures of behavior. The profiles of acute effects produced by TCE and ether were similar to one another and similar to the profile of effects produced by the IP administration of ethanol. This profile of depressant effects included changes in posture, decreased arousal, disturbances in gait, decreased forelimb grip strength, increased landing foot splay, and impaired psychomotor coordination. Flurothyl exposure also produced dose-related effects on many of the measures in the FOB; however, unlike the depressant vapors, flurothyl did not affect measures of muscle tone and equilibrium such as forelimb grip strength and landing foot splay, or measures of sensorimotor reactivity, including the touch response and tail pinch response. In addition, flurothyl produced handling-induced convulsions in some mice. Recovery from the acute effects of these vapors was rapid and began within minutes of removal from the exposure chamber. These results provide further evidence that exposure to certain solvents produces a profile of reversible effects qualitatively similar to that produced by depressant drugs and alcohol, and that the FOB can be used to compare and contrast profiles of depressant and excitatory effects of inhalants.

Animals↗

Effects of dorsal noradrenergic bundle lesions on recovery after sensorimotor cortex injury.

Several lines of evidence suggest that the recovery of the ability of rats to traverse a narrow beam after unilateral injury to the sensorimotor cortex is noradrenergically mediated. We tested the hypotheses that the influence of norepinephrine on beam-walking recovery occurs, at least partially, through effects in the contralateral and/or ipsilateral cerebral cortex. Rats had either a selective left or right 6-hydroxydopamine lesion or sham lesion of the dorsal noradrenergic bundle (DNB) 2 weeks before suction-ablation or sham injury of the right sensorimotor cortex. The rats' abilities to perform the beam-walking task were measured over the 10 days following cortex surgery. DNB lesions did not affect the initial severity of the beam-walking deficit and had no effect on the performance of the task in rats with sham cortex injuries. Lesions of the contralateral but not ipsilateral DNB significantly impaired recovery. Further, in cortically lesioned rats with contralateral DNB lesions, norepinephrine content in the cerebral cortex opposite to the sensorimotor cortex lesion was significantly correlated with recovery. These data suggest that the effect of norepinephrine on recovery of beam-walking ability may be partially exerted in the cerebral cortex contralateral to the injury.

Animals↗

Gastric pathology and aphagia following lateral hypothalamic lesions in rats: effects of preoperative weight reduction.

The body weights of male albino rats were reduced gradually to 80% of normal body weight by resricting food intake (dieting), and then the rats were given lateral hypothalamic (LH) lesions. Compared with rats of normal body weight sustaining similar brain lesions, the dieted group displayed a shorter period of postoperative aphagia and less gastric pathology. In a second experiment, a group of rats was reduced to 80% of normal body weight by withholding all food (fasting) and then given LH lesions. Compared with dieted rats sustaining similar brain damage, the fasted group displayed a longer period of post operative aphagia and greater gastric pathology. Since the duration of aphagia could be shortened or lengthened by simple manipulations of preoperative body weight, the adequacy of sensorimotor or motivational hypotheses to account for aphagia is questioned. The results are more consistent with the suggestion that gastric abnormalities produced by LH lesions inhibit eating.

Animals↗