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PubMed1984

Sensorimotor impairment and elevated levels of dopamine metabolites in the neostriatum occur rapidly after intranigral injection of 6-hydroxydopamine or gamma-hydroxybutyrate in awake rats.

The unilateral injection of 6-hydroxydopamine (8 micrograms) into the ventral tegmental area of awake rats produced a rapidly developing and irreversible sensory neglect to contralateral tactile stimuli. This neglect developed in a caudal to rostral direction on the affected body surface and coincided with significant elevation in the concentrations of dopamine and two of its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the ipsilateral neostriatum. The unilateral injection of procaine or gamma-hydroxybutyric acid (GHB) into the substantia nigra of awake animals also produced a contralateral neglect that developed in a caudal to rostral direction, but the behavioral effect of these drugs diminished within 1 hr. Concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the neostriatum were markedly elevated during continuous infusions of procaine or gamma-hydroxybutyric acid. The extent of sensory neglect and changes in dopamine metabolism in the neostriatum varied according to the amount of gamma-hydroxybutyric acid injected into the nigra and according to the proximity of injections of gamma-hydroxybutyric acid to the pars compacta. The rapid onset of sensory neglect following microinjections of 6-hydroxydopamine, procaine or gamma-hydroxybutyric acid is consistent with the ability of each of these drugs to block the conduction of impulses in mesostriatal neurons and suggests that concomitant increases in levels of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the neostriatum resulted from decreases in the release of dopamine coupled with increased synthesis of dopamine. These findings also indicate that the catabolism of dopamine to dihydroxyphenylacetic acid or homovanillic acid may originate intraneuronally, without prior release of dopamine and its recapture by mesostriatal terminals, if the flow of impulses in this pathway has been blocked.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Non-linear development of postural control and strategy use in young children: a longitudinal study.

This longitudinal analysis confirmed a non-monotonic pattern of postural control development in children from age 5 to 8 years suggested by previous cross-sectional studies. Postural control was considered in terms of control strategy and its variability operationalized by mean and standard deviation of center of pressure (COP) velocity; and of effectiveness and its variability operationalized by mean and standard deviation of COP anteroposterior (a-p) excursion. Periods of significant variability were used to indicate behavioral transitions. Seventeen healthy children (nine males, eight females) aged 5-6 years (61.5-75 months) were tested at 3- to 4-month intervals up to age 8 years (83-97 months) in eyes-open quiet stance on a force platform for 30 s in each of ten trials. Data were reorganized into six developmental categories based on adjacent test dates prior to (-1) and after (+1, +2, +3, +4) a subject's trial with the lowest COP velocity (0). Developmental category is proposed to represent level of sensorimotor integrative skill. Within-subject ANCOVAs revealed a significant effect (P<0.0001) for developmental category with covariance due to height, weight and actual age removed. Post hoc tests showed a significant effect (P<0.0001) on measures of strategy. However, differences in COP velocity (type of strategy used) and differences in its variability (denoting a transition between strategies) were not always coincident. Performance outcome (COP a-p excursion) changed near linearly across categories. It was concluded that a non-monotonic change in control strategy as indicated by COP velocity describes the development of quiet stance equilibrium. A transition occurs from a primarily open-loop to incorporation of open- and closed-loop components of control. Honing of strategy used precedes and follows transitions. Constriction of velocity and excursion may typify the early stages of bimodal strategy. Developmental categories describe affiliation with the strategy employed and may represent differentiable levels of sensorimotor integrative skill. They may be more useful in assessing progression of equilibrium control than consecutive age in years.

Adaptation, Physiological↗
PubMed2005

Clinical features of argyrophilic grain disease: a retrospective survey of cases with neuropsychiatric symptoms.

OBJECTIVE: Although argyrophilic grain disease (AGD) appears common in post-mortem series, its clinical features are not widely known. The aim of this study was to explore such clinical features in neuropathologically-confirmed AGD cases. METHODS: After completing a neuropathological assessment of 386 patients, 33 cases (8.5%) were diagnosed as having AGD; 10 were diagnosed as "pure" cases. These subjects had been admitted to geriatric wards of mental hospitals because of behavioral or neuropsychiatric symptoms requiring medical management. Assessment of the clinical features of the pure cases was based on the evaluations in medical records. RESULTS: The average age at onset was 82.2 years. Amnesia was the most common initial symptom; irritability and agitation were also common as initial symptoms. During the course of the illness, irritability was the most frequently observed, followed by delusions (mostly delusions of persecution), dysphoria, and then agitation, and apathy. In contrast to the severity of amnesia, other cognitive functions were relatively spared, and the sensorimotor symptoms were not remarkable. CONCLUSIONS: AGD is a late-onset dementing disorder clinically characterized by amnesia, with other cognitive functions relatively spared, and prominent neuropsychiatric features. These features may correlate with the high level of AGD seen in limbic structures. Future studies are needed to elucidate whether these features are common to all AGD patients or to a clinical subtype with neuropsychiatric symptoms.

Aged↗
PubMed2004

Cellular, circuit, and synaptic mechanisms in song learning.

Songbirds, much like humans, learn their vocal behavior, and must be able to hear both themselves and others to do so. Studies of the brain areas involved in singing and song learning could reveal the underlying neural mechanisms. Here we describe experiments that explore the properties of the songbird anterior forebrain pathway (AFP), a basal ganglia-forebrain circuit known to be critical for song learning and for adult modification of vocal output. First, neural recordings in anesthetized, juvenile birds show that auditory AFP neurons become selectively responsive to the song stimuli that are compared during sensorimotor learning. Individual AFP neurons develop tuning to the bird's own song (BOS), and in many cases to the tutor song as well, even when these stimuli are manipulated to be very different from each other. Such dual selectivity could be useful in the BOS-tutor song comparison critical to song learning. Second, simultaneous neural recordings from the AFP and its target nucleus in the song motor pathway in anesthetized adult birds reveal correlated activity that is preserved through multiple steps of the circuits for song, including the AFP. This suggests that the AFP contains highly functionally interconnected neurons, an architecture that can preserve information about the timing of firing of groups of neurons. Finally, in vitro studies show that recurrent synapses between neurons in the AFP outflow nucleus, which are expected to contribute importantly to AFP correlation, can undergo activity-dependent and timing-sensitive strengthening. This synaptic enhancement appears to be restricted to birds in the sensory critical and early sensorimotor phases of learning. Together, these studies show that the AFP contains cells that reflect learning of both BOS and tutor song, as well as developmentally regulated synaptic and circuit mechanisms well-suited to create temporally organized assemblies of such cells. Such experience-dependent sensorimotor assemblies are likely to be critical to the AFP's role in song learning. Moreover, studies of such mechanisms in this basal ganglia circuit specialized for song may shed light more generally on how basal ganglia circuits function in guiding motor learning using sensory feedback signals.

Animals↗
PubMed2005

Schema-based learning of adaptable and flexible prey- catching in anurans II. Learning after lesioning.

The previous companion paper describes the initial (seed) schema architecture that gives rise to the observed prey-catching behavior. In this second paper in the series we describe the fundamental adaptive processes required during learning after lesioning. Following bilateral transections of the hypoglossal nerve, anurans lunge toward mealworms with no accompanying tongue or jaw movement. Nevertheless anurans with permanent hypoglossal transections eventually learn to catch their prey by first learning to open their mouth again and then lunging their body further and increasing their head angle. In this paper we present a new learning framework, called schema-based learning (SBL). SBL emphasizes the importance of the current existent structure (schemas), that defines a functioning system, for the incremental and autonomous construction of ever more complex structure to achieve ever more complex levels of functioning. We may rephrase this statement into the language of Schema Theory (Arbib 1992, for a comprehensive review) as the learning of new schemas based on the stock of current schemas. SBL emphasizes a fundamental principle of organization called coherence maximization, that deals with the maximization of congruence between the results of an interaction (external or internal) and the expectations generated for that interaction. A central hypothesis consists of the existence of a hierarchy of predictive internal models (predictive schemas) all over the control center-brain-of the agent. Hence, we will include predictive models in the perceptual, sensorimotor, and motor components of the autonomous agent architecture. We will then show that predictive models are fundamental for structural learning. In particular we will show how a system can learn a new structural component (augment the overall network topology) after being lesioned in order to recover (or even improve) its original functionality. Learning after lesioning is a special case of structural learning but clearly shows that solutions cannot be known/hardwired a priori since it cannot be known, in advance, which substructure is going to break down.

Animals↗
PubMed1999

Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5.

We investigated the role of NMDA receptors in memory encoding and retrieval. A delayed matching-to-place (DMP) paradigm in the watermaze was used to examine 1-trial spatial memory in rats. Over periods of up to 21 days, 4 daily trials were given to an escape platform hidden in a new location each day, with the memory interval (ITI) varying from 15 sec to 2 hours between trials 1 and 2, but always at 15 sec for the remaining ITIs. Using chronic i.c.v. infusions of D-AP5, acute intrahippocampal infusions, ibotenate hippocampus + dentate lesions and relevant aCSF or sham surgery control groups, we established: (1) the DMP task is hippocampal-dependent; (2) D-AP5 causes a delay-dependent impairment of memory in which the Groups x Delay interaction was significant on two separate measures of performance; (3) this memory impairment also occurs with acute intrahippocampal infusions; (4) the impairment occurs irrespective of whether the animals stay in or are removed from the training context during the memory delay interval; and (5) D-AP5 affects neither the retrieval of information about the spatial layout of the environment, nor memory of where the escape platform had been located on the last day before the start of chronic D-AP5 infusion. LTP in vivo in the dentate gyrus was blocked in the chronically-infused D-AP5 rats and HPLC measurements at sacrifice revealed appropriate intrahippocampal levels. Acute intrahippocampal infusion of radiolabelled D-AP5 revealed relatively restricted diffusion and was used to estimate whole-tissue hippocampal drug concentrations. These results indicate that (1) short-term memory for spatial information is independent of NMDA receptors; (2) the rapid consolidation of spatial information into long-term memory requires activation of hippocampal NMDA receptors; (3) NMDA receptors are not involved in memory retrieval; and (4) the delay-related effects of NMDA receptor antagonists on performance of this task cannot be explained in terms of sensorimotor disturbances. The findings relate to the idea that hippocampal synaptic plasticity is involved in event-memory (Morris and Frey, Phil Trans R Soc Lond B 1997;352:1489-1503) and to a computational model of one-trial DMP performance of Foster et al. (unpublished data).

2-Amino-5-phosphonovalerate↗
PubMed1993

Selective effects of low-dose D2 dopamine receptor antagonism in a reaction-time task in rats.

Operant responses involving a cued discrimination are sensitively disrupted by neuroleptic drugs that block dopamine (DA) receptors in the brain; however, it is not clear which DA receptor subtypes may be involved in these effects. The role of D1 or D2 DA receptor antagonists on the execution of a conditioned reaction-time (RT) motor task was investigated in the present study. Rats were trained to release a lever after the presentation of a visual cue within a RT limit to be reinforced by a food pellet. The D1 receptor antagonist SCH-23390, at doses that significantly decrease the behavioral effects of cocaine, did not impair performance at any dose (5, 10, or 20 micrograms/kg) injected subcutaneously. In contrast, a selective D2 receptor antagonist raclopride (50, 100, or 200 micrograms/kg) induced a dose-dependent increase in the number of incorrect responses (release of the lever over the RT limit) associated with an increase in the RT. The results suggest that the dopaminergic nigrostriatal system, which has previously been shown to be specifically involved in this RT task (Amalric and Koob 1987), appears to be a sensitive site for sensorimotor integration, and that the execution of the conditioned RT motor task may depend preferentially on the activation of the dopaminergic D2 receptors in this system.

Animals↗
PubMed1986

Clinical and EEG features of complex partial seizures of extratemporal origin.

Complex partial seizures (CPSs) of extratemporal origin are frequently misdiagnosed. Common reasons for diagnostic errors are failure to recognize the epileptic cause of the attacks or to appreciate localizing clinical seizure characteristics and nonspecific or misleading scalp EEG findings. This report describes clinical characteristics of two types of extratemporal CPSs, frontal and occipital. Frontal lobe CPSs are brief, frequent attacks that begin and end suddenly. They are dominated by complex, semi-purposeful motor automatisms, and vocalization and sexual automatisms are common. Their often bizarre appearance frequently leads to a misdiagnosis of hysteria. Occipital lobe CPSs are characterized primarily by their spread pattern, which can follow various paths. They may mimic temporal lobe CPSs, sensorimotor partial seizures, or supplementary motor partial seizures. Scalp EEGs are frequently misleading. The initial clinical symptoms are the most important clue to correct diagnosis and include elemental visual symptoms, visual loss, eye pulling or movement sensations in the absence of detectable movement, rapid forced blinking or eye flutter, and contralateral eye deviation.

Adult↗
PubMed1987

Neuronal control of bird song production.

Bird song represents a powerful model system for many of the important problems in behavioral neurobiology, offering both easily measured sensory and motor patterns and a discrete neural effector system. Methods were developed to record the discharge of neurons in singing birds to examine the functions of nuclei in the song control pathway previously implicated anatomically. In several cases, lesions and other techniques were employed to test predictions derived from electrode recordings. Four major findings emerge from these studies. Single-unit recordings from telencephalic nucleus hyperstriatum ventrale, pars caudale (HVc) show several classes of neurons with apparently specialized roles in song production and/or sensorimotor interaction. The nucleus interfacialis (Nlf; Nottebohm, 1980), which provides an input to HVc and is anatomically the "highest" nucleus in the descending motor pathway, is uniquely placed among vocal control nuclei to be a generator of timing cues for song. Consistent with the unidirectional connections between nuclei of the descending pathway, Nlf, HVc, and nucleus robustus archistriatalis (RA) are activated sequentially prior to sound onset. Three other nuclei with connections to or from the descending tract do not show song-related activity in the adult. Bilateral HVc recordings and peripheral disruptions of the vocal apparatus suggest that both hemispheres and syringeal halves normally make similar contributions to most if not all song syllables. The latter finding casts doubt on the analogy between neural lateralization in bird song and in human speech.

Action Potentials↗
PubMed1994

Neural network models of cortical functions based on the computational properties of the cerebral cortex.

We describe a biologically plausible modelling framework based on the architectural and processing characteristics of the cerebral cortex. Its key feature is a multicellular processing unit (cortical column) reflecting the modular nature of cortical organization and function. In this framework, we describe a neural network model organization and function. In this framework, we describe a neural network model of the neuronal circuits of the cerebral cortex that learn different functions associated with different parts of the cortex: 1) visual integration for invariant pattern recognition, performed by a cooperation between temporal and parietal areas; 2) visual-to-motor transformation for 3D arm reaching movements, performed by parietal and motor areas; and 3) temporal integration and storage of sensorimotor programs, performed by networks linking the prefrontal cortex to associative sensory and motor areas. The architecture of the network is inspired from the features of the architecture of cortical pathways involved in these functions. We propose two rules which describe neural processing and plasticity in the network. The first rule (adaptive tuning if gating) is an analog of operant conditioning and permits to learn to anticipate an action. The second rule (adaptive timing) is based on a bistable state of activity and permits to learn temporally separate events forming a behavioral sequence.

Cerebral Cortex↗
PubMed1994

Spatial localization in the Morris water maze in rats: acquisition is affected by intra-accumbens injections of the dopaminergic antagonist haloperidol.

Previous studies (G. E. Ploeger, B. M. Spruijt, & A. R. Cools, 1992) showed that low doses of systemically injected haloperidol affected spatial learning in the Morris water maze. This study investigated effects of intra-accumbens injections of haloperidol on spatial learning. To control for motivation and sensorimotor coordination, the researchers trained the rats to escape onto a visible platform. Low doses (50-100 ng) of haloperidol impaired spatial learning, whereas escaping on a visible platform was undisturbed. The 500-ng dose of haloperidol completely blocked acquisition because of combined learning and motor impairments. Retrieval of an acquired escape response was unaffected by 500 ng haloperidol. The data show that mesolimbic dopaminergic activity is involved in the acquisition of spatial localization. The results are related to studies demonstrating the involvement of the nucleus accumbens in cue-directed behaviors.

Animals↗
PubMed1997

A revolving food pellet test for measuring sensorimotor performance in rats.

A revolving food pellet (RFP) test is presented, measuring the ability of rats to eat food pellets suspended from a horizontal bar in their home cage. This easy to make and economical device evaluates the efficiency of bilateral front paw coordination while standing. During the beginning of a ten day testing period, rats exposed to the RFP chamber had a lower intake of food and decreased body weight than rats housed in a standard home cage. With continued practice, the experimental group increased their food intake and body weight. During this time, the rats learned to control the revolving pellets by stabilizing them with their front paws and chewing on them. This apparatus is suitable for assessing a form of sensorimotor learning, involving the efficiency of front paw reaching, grasping, and holding movements, together with appropriate postural adjustments and biting movements. This test was sensitive to brain lesioning, as rats with bilateral lesions of the cerebellar fastigial nucleus were impaired.

Animals↗
PubMed1983

Intracerebral grafting of neuronal cell suspensions. V. Behavioural recovery in rats with bilateral 6-OHDA lesions following implantation of nigral cell suspensions.

Bilateral 6-hydroxydopamine-induced lesions of the ascending forebrain dopamine neurones induce a behavioural syndrome in rats which includes profound aphagia, adipsia, akinesia and bilateral sensorimotor neglect. Such animals will die unless maintained by intragastric feeding. Three experiments are reported in which we have attempted to ameliorate this syndrome with single or multiple placements of nigral cell suspensions into the forebrains of rats with bilateral dopamine depletions. Although the grafts were efficient in reversing the sensorimotor and akinetic impairments, and produced a significant increase in eating, the grafted rats remained hypophagic and adipsic. The results indicate that although many components of the bilateral dopamine denervation syndrome can be reversed by intrastriatal nigral suspension grafts, the severe eating and drinking deficits remain unameliorated.

Animals↗
PubMed1994

Impairment in the acquisition of passive and active avoidance learning tasks due to bilateral entorhinal cortex lesions.

The relationship between the entorhinal cortex and learning behavior was examined. The initial stage of Alzheimer's disease has been shown to be characterized by neuropathological alteration in the entorhinal cortex, with the appearance of the greatest number of neuronal tangles and severe neuronal loss in comparison with other brain regions involved. This entorhinal cortex, because of its anatomical relationship to the hippocampus, may play a crucial role in memory formation. In this study, rats with bilateral ibotenic acid-induced lesions of the entorhinal cortices were tested for acquisition of passive and active avoidance learning tasks. These animals displayed no sensorimotor disturbances as shown by evaluation of locomotor activity and shock sensitivity. However, they did show impair acquisition of passive and active avoidance responses. On the other hand, when the lesions were induced after training, there was no extinction of the acquired passive and active avoidance responses. The results demonstrate the importance of the entorhinal cortex in learning acquisition and indicate that rats with partial neuronal loss in the entorhinal cortex may be a useful model for studying the memory disturbance of Alzheimer's disease.

Animals↗
PubMed1997

Behavioural specificity of neocortical grafts of fetal basal forebrain tissue after unilateral lesion of the nucleus basalis with alpha-amino-3-OH-4-isoxozole propionic acid (AMPA).

The previous articles in this series [4,9] have shown that unilateral AMPA lesions of the nucleus basalis magnocellularis (nbm) produced widespread morphological and functional changes to the forebrain cholinergic projection system that could be reversed by transplants of fetal cholinergic tissue. At earlier postgraft time points, the effects of cholinergic grafts were specific to the neocortical region (frontal or parietal cortex) into which the grafts were targeted. Here we report that nbm lesion-induced spatial learning and memory deficits in the Morris water maze were reversed at 6-8 weeks postsurgery only by cholinergic grafts placed in the frontal cortex or frontal and parietal cortices combined. Similar grafts to parietal cortex only and noncholinergic fetal transplants to any cortical site were ineffective. In contrast, using separate groups of animals, deficits in sensorimotor function could be reversed in only one measure (open field turning) by cholinergic transplants targeted to the parietal (somatosensory) cortex or frontal and parietal cortex combined. These behavioural dissociations demonstrate that the frontal cortical cholinergic innervation from the nbm is necessary for effective spatial cognitive performance.

Animals↗
PubMed1975

Trigeminal deafferentation and hunger in the pigeon (Columbia livia).

The location and distribution of the pigeon's trigeminal nerve permit deafferentation of the oral region without affecting motor functions. Although trigeminal deafferentation does not affect drinking, it reduces the efficiency of the consummatory response of eating and disrupts motivational processes underlying hunger and weight regulation. Although the two types of deficit may be experimentally dissociated, trigeminal deafferentation invariably affects both sensorimotor and motivational mechanisms. The deficits in food intake and weight regulation seen after trigeminal deafferentation in the pigeon resemble some components of the "lateral hypothalamic syndrome" in the rat. The results are related to recent studies of the contribution of peripheral and central oropharyngeal factors to the neural control of food intake in both rat and pigeon.

Animals↗
PubMed1982

Electrophysiological properties of neocortical neurons in vitro.

1. Intracellular recordings were obtained from neurons of the guinea pig sensorimotor cortical slice maintained in vitro. Under control recording conditions input resistances, time constants, and spiking characteristics of slice neurons were well within the ranges reported by other investigators for neocortical neurons in situ. However, resting potentials (mean of -75 mV) and spike amplitudes (mean of 93.5 mV) were 10-25 mV greater than has been observed in intact preparations. 2. Current-voltage relationships obtained under current clamp revealed a spectrum of membrane-rectifying properties at potentials that were subthreshold for spike generation. Ionic and pharmacologic analyses suggest that subthreshold membrane behavior is dominated by voltage-sensitive, very slowly inactivating conductances to K+ and Na+. 3. Action potentials were predominantly Na+ dependent under normal conditions but when outward K+ currents were reduced pharmacologically, it was possible, in most cells, to evoke a non-Na+-dependent, tetrodotoxin-(TTX) insensitive spike, which was followed by a prominent depolarizing after-potential. Both of these events were blocked by the Ca2+ current antagonists, Co2+ and Mn2+. 4. A small population of neurons generated intrinsic, all-or-none burst potentials when depolarized with current pulses or by synaptic activation. These cells were located at a narrow range of depths comprising layer IV and the more superficial parts of layer V. 5. Spontaneous excitatory synaptic potentials appeared in all neurons. Spontaneous inhibitory events were visible in only about 10% of the cells, and in those cases apparently reversed polarity at a level slightly positive to resting potential. Stimulation of the surface of the slice at low intensities evoked robust and usually concurrent excitatory and inhibitory synaptic potentials. Unitary inhibitory postsynaptic potentials (IPSPs) reversed at levels positive to rest. Stronger stimulation produced a labile, long-duration, hyperpolarizing IPSP with a reversal potential 15-20 mV negative to the resting level. 6. Neocortical neurons in vitro retain the basic membrane and synaptic properties ascribed to them in situ. However, the array of passive and active membrane behavior observed in the slice suggests that cortical neurons may be differentiated by specific functional properties as well as by their extensive morphological diversity.

Action Potentials↗
PubMedDate not supplied

[The time of a complex sensorimotor choice reaction in subjects with differing functional mobility of the nervous processes].

In 246 subjects (men, mean age--21 years) differing by the level of functional mobility (I-IV), statistically significant differences were found of mean values of latencies of complex sensorimotor reactions of choice (differentiation by meaning). Computation of Pearson correlation coefficients revealed significant negative connections between characteristics of functional mobility and values of latencies. On the basis of these data it is possible to consider the value of the latency of complex semantic reactions of choice as an information index of functional mobility of nervous processes.

Adult↗