3-Acetylpyridine-induced ataxic-like motor impairments are associated with plastic changes in the Purkinje cells of the rat cerebellum.

Ataxias are characterized by aberrant movement patterns closely related to cerebellar dysfunction. Purkinje cell axons are the sole outputs from the cerebellar cortex, and dysfunctional activity of Purkinje cells has been associated with ataxic movements. However, the synaptic characteristics of Purkinje cells in cases of ataxia are not yet well understood. The nicotinamide antagonist 3-acethylpyridine (3-AP) selectively destroys inferior olivary nucleus neurons so it is widely used to induce cerebellar ataxia. Five days after 3-AP treatment (65mg/kg) in adult male Sprague-Dawley rats, motor incoordination was revealed through BBB and Rotarod testing. In addition, in Purkinje cells from lobules V-VII of the cerebellar vermis studied by the Golgi method, the density of dendritic spines decreased, especially the thin and mushroom types. Western blot analysis showed a decrease in AMPA and PSD-95 content with an increase of the α-catenin protein, while GAD-67 and synaptophysin were unchanged. Findings suggest a limited capacity of Purkinje cells to acquire and consolidate afferent excitatory inputs and an aberrant, rigid profile in the movement-related output patterns of Purkinje neurons that likely contributes to the motor-related impairments characteristic of cerebellar ataxias.

Espinogénesis en motoneuronas de la médula espinal tras la lesión farmacológica de la corteza motora de ratas / Spinogenesis in spinal cord motor neurons following pharmacological lesions to the rat motor cortex

INTRODUCCIÓN: Diversas enfermedades neuropatologías asociadas a la degeneración del tracto corticoespinal muestran deterioro de las funciones motoras. Tales alteraciones neurológicas se asocian a diversos fenómenos plásticos subsecuentes, a nivel tanto presináptico como postsináptico. Sin embargo, no existe evidencia que indique la existencia de modificaciones en la transmisión de información del tracto corticoespinal a las motoneuronas espinales. MÉTODOS: Se indujo una lesión por vía estereotáxica en la corteza motora primaria de ratas hembra adultas con ácido kaínico y, 15 días después, se evaluó el desempeño motor mediante la escala BBB y en un dispositivo Rota-Rod. Paralelamente, se cuantificó la densidad numérica y proporcional de las espinas delgadas, en hongo y gordas, en motoneuronas de un segmento torácico-lumbar de la médula espinal. Así mismo, se registró la expresión de las proteínas espinofilina, sinaptofisina β III-tubulina. RESULTADOS: La lesión farmacológica provocó un desempeño motor deficiente. Así mismo, tanto la densidad de espinas como la proporción de espinas delgadas y gordas fue mayor, al igual que la expresión de las 3 proteínas estudiadas. CONCLUSIÓN: La aparición de los síntomas clínicos de daño neurológico provocado por la degeneración walleriana del tracto corticoespinal se acompaña de respuestas plásticas espontáneas de tipo compensador, a nivel sináptico. Lo anterior indica que durante la rehabilitación temprana de este tipo de pacientes, la plasticidad espontánea constituye un factor que se debe considerar para el diseño de estrategias de intervención más eficientes

INTRODUCTION: Motor function is impaired in multiple neurological diseases associated with corticospinal tract degeneration. Motor impairment has been linked to plastic changes at both the presynaptic and postsynaptic levels. However, there is no evidence of changes in information transmission from the cortex to spinal motor neurons. METHODS: We used kainic acid to induce stereotactic lesions to the primary motor cortex of female adult rats. Fifteen days later, we evaluated motor function with the BBB scale and the rotarod and determined the density of thin, stubby, and mushroom spines of motor neurons from a thoracolumbar segment of the spinal cord. Spinophilin, synaptophysin, and β III-tubulin expression was also measured. RESULTS: Pharmacological lesions resulted in poor motor performance. Spine density and the proportion of thin and stubby spines were greater. We also observed increased expression of the 3 proteins analysed. CONCLUSION: The clinical symptoms of neurological damage secondary to Wallerian degeneration of the corticospinal tract are associated with spontaneous, compensatory plastic changes at the synaptic level. Based on these findings, spontaneous plasticity is a factor to consider when designing more efficient strategies in the early phase of rehabilitation

Spinogenesis in spinal cord motor neurons following pharmacological lesions to the rat motor cortex. / Espinogénesis en motoneuronas de la médula espinal tras la lesión farmacológica de la corteza motora de ratas.

INTRODUCTION: Motor function is impaired in multiple neurological diseases associated with corticospinal tract degeneration. Motor impairment has been linked to plastic changes at both the presynaptic and postsynaptic levels. However, there is no evidence of changes in information transmission from the cortex to spinal motor neurons. METHODS: We used kainic acid to induce stereotactic lesions to the primary motor cortex of female adult rats. Fifteen days later, we evaluated motor function with the BBB scale and the rotarod and determined the density of thin, stubby, and mushroom spines of motor neurons from a thoracolumbar segment of the spinal cord. Spinophilin, synaptophysin, and ß iii-tubulin expression was also measured. RESULTS: Pharmacological lesions resulted in poor motor performance. Spine density and the proportion of thin and stubby spines were greater. We also observed increased expression of the 3 proteins analysed. CONCLUSION: The clinical symptoms of neurological damage secondary to Wallerian degeneration of the corticospinal tract are associated with spontaneous, compensatory plastic changes at the synaptic level. Based on these findings, spontaneous plasticity is a factor to consider when designing more efficient strategies in the early phase of rehabilitation.

Plastic changes to dendritic spines in the cerebellar and prefrontal cortices underlie the decline in motor coordination and working memory during successful aging.

Old age is the last stage of life and by taking a multidimensional view of aging, Neuroscientists have been able to characterize pathological or successful aging. Psychomotor and cognitive performance are recognized as two major domains of successful aging, with a loss of motor coordination and working memory deficits two of the most characteristic features of elderly people. Dendritic spines in both the cerebellar and prefrontal cortices diminish in aging, yet the plastic changes in dendritic spines have not been related to behavioral performance neither the changes in the cerebellar or prefrontal cortices. As such, motor coordination and visuospatial working memory (vsWM) was evaluated here in aged, 22-month-old rats, calculating the density of spines and the proportion of the different types of spines. These animals performed erratically and slowly in a motor coordination-related paradigm, and the vsWM was resolved deficiently. Spine density was reduced in aged animals, and the proportional density of each of the spine types studied diminished in both the brain regions studied. The loss of dendritic spines and particularly, the changes in the proportional density of the different spine types could underlie, at least in part, the behavioral deficits observed during aging. To our knowledge, this is the first study of the plastic changes in different dendritic spine types that might underlie the behavioral alterations in motor and cognitive abilities associated with aging. Further neurochemical and molecular studies will help better understand the functional significance of the plastic changes to dendritic spines in both successful and pathological aging.

El aprendizaje motor induce cambios plásticos en las espinas dendríticas de las células de Purkinje del cerebelo de ratas / No disponible

INTRODUCCIÓN: El lóbulo paramediano del cerebelo está involucrado en el desempeño correcto de las habilidades motoras a través de la práctica. Las espinas dendríticas son estructuras dinámicas que regulan la estimulación sináptica excitadora. En este trabajo se estudiaron los posibles cambios plásticos en espinas de células de Purkinje del lóbulo paramediano cerebelar de ratas, durante el aprendizaje motor. MÉTODOS: Se entrenaron a ratas macho adultas durante un período de seis días, en un paradigma de aprendizaje motor acrobático y se cuantificó tanto la densidad como los tipos de espinas dendríticas en cada uno de los seis días de estudio, mediante una modificación al método de Golgi. RESULTADOS: La curva de aprendizaje reflejó una disminución consistente de los errores cometidos en el transcurso de los días de entrenamiento. Así mismo, se observaron más espinas dendríticas en los días 2 y 6 y, en particular, más espinas delgadas en los días 1, 3 y 6, menos espinas en hongo el día 3, menos espinas gordas el día 1 y más espinas anchas los días 4 y 6. CONCLUSIÓN: El período inicial de aprendizaje motor podría estar asociado con el procesamiento rápido de la información sináptica subyacente y con un aparente «silenciamiento» de los procesos de consolidación mnémica, en una base de regulación de la excitabilidad neuronal

INTRODUCTION: The paramedian lobule of the cerebellum is involved in learning to correctly perform motor skills through practice. Dendritic spines are dynamic structures that regulate excitatory synaptic stimulation. We studied plastic changes occurring in the dendritic spines of Purkinje cells from the paramedian lobule of rats during motor learning. METHODS: Adult male rats were trained over a 6-day period using an acrobatic motor learning paradigm; the density and type of dendritic spines were determined every day during the study period using a modified version of the Golgi method. RESULTS: The learning curve reflected a considerable decrease in the number of errors made by rats as the training period progressed. We observed more dendritic spines on days 2 and 6, particularly more thin spines on days 1, 3, and 6, fewer mushroom spines on day 3, fewer stubby spines on day 1, and more thick spines on days 4 and 6. CONCLUSION: The initial stage of motor learning may be associated with fast processing of the underlying synaptic information combined with an apparent "silencing" of memory consolidation processes, based on the regulation of the neuronal excitability

Motor learning induces plastic changes in Purkinje cell dendritic spines in the rat cerebellum. / El aprendizaje motor induce cambios plásticos en las espinas dendríticas de las células de Purkinje del cerebelo de ratas.

INTRODUCTION: The paramedian lobule of the cerebellum is involved in learning to correctly perform motor skills through practice. Dendritic spines are dynamic structures that regulate excitatory synaptic stimulation. We studied plastic changes occurring in the dendritic spines of Purkinje cells from the paramedian lobule of rats during motor learning. METHODS: Adult male rats were trained over a 6-day period using an acrobatic motor learning paradigm; the density and type of dendritic spines were determined every day during the study period using a modified version of the Golgi method. RESULTS: The learning curve reflected a considerable decrease in the number of errors made by rats as the training period progressed. We observed more dendritic spines on days 2 and 6, particularly more thin spines on days 1, 3, and 6, fewer mushroom spines on day 3, fewer stubby spines on day 1, and more thick spines on days 4 and 6. CONCLUSION: The initial stage of motor learning may be associated with fast processing of the underlying synaptic information combined with an apparent "silencing" of memory consolidation processes, based on the regulation of the neuronal excitability.