Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knock-out mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects.

Estructura y distribución de la íctiofauna de la subcuenca del río Acahuapa, San Vicente, El Salvador

Los ecosistemas fluviales brindan al ser humano importantes bienes ambientales como el abastecimiento de agua para consumo, producción de alimento, generación de energía hidroeléctrica, navegación, recreación y pesca. Así mismo proveen importantes servicios ecosistémicos al regular el clima y los gases del efecto invernadero a través del ciclo hidrológico y el ciclaje de nutrientes (Welcomme 1992). Los peces constituyen uno de los taxones más importantes dentro de los ecosistemas fluviales, además de constituir la mayor cantidad de biomasa animal, desempeñan papeles ecológicos relevantes en el flujo energético de la cadena trófica. Es por ello que en los últimos años ha surgido mayor interés por estudiar a este grupo, lo que ha permitido tener mayor comprensión de su historia natural, sus interacciones y relaciones con los factores ambientales (Miller 2009). La estructura y distribución de la íctiofauna del río Acahuapa fue analizada en 17 sitios dentro del cauce principal y en ríos afluentes. Los muestreos se realizaron en junio, agosto, noviembre del 2011 y febrero y abril del 2012. Se capturó 6,742 individuos distribuidos en 8 órdenes, 13 familias y 32 especies. El 47% de las especies son secundarios, 41% periféricas y 12% primarias. Según clasificación por presencia se obtuvo el 59% de las especies como migratoria, 31% como estacionales y 10% como residentes. Se compararon tallas de 10 especies con mayor abundancia y dominancia por sitios de muestreo donde se observó diferencias significativas de Agonostomus monticola, Astyanax aeneus, Poecilia gillii, Poecilia salvatoris, Rhamdia guatemalensis, Rhamdia laticauda y Sicydium multipunctatum por estratificación de altura. En el caso de A. monticola y S. multipunctatum se observó diferencia de tallas que responde a comportamientos migratorios dentro de la subcuenca.

ROLE OF THE FRONTAL EYE FIELD, SUPERIOR COLLICULUS, AND BASAL GANGLIA IN FLEXIBLE SACCADE BEHAVIOR

A distributed network of cortical and subcortical brain regions mediates the control of voluntary behavior, but it is unclear how this complex system may flexibly shift between different behavioral events. This thesis describes the neurophysiological changes in several key nuclei across the brain during flexible behavior, using saccadic eye movements in rhesus macaque monkeys. We examined five nuclei critical for saccade initiation and modulation: the frontal eye field (FEF) in the cerebral cortex, the subthalamic nucleus (STN), caudate nucleus (CD), and substantia nigra pars reticulata (SNr) in the basal ganglia (BG), and the superior colliculus (SC) in the midbrain. The first study tested whether a ‘threshold’ theory of how neuronal activity cues saccade initiation is consistent with the flexible control of behavior. The theory suggests there is a fixed level of FEF and SC neuronal activation at which saccades are initiated. Our results provide strong evidence against a fixed saccade threshold in either structure during flexible behavior, and indicate that threshold variability might depend on the level of inhibitory signals applied to the FEF or SC. The next two studies investigated the BG network as a likely candidate to modulate a saccade initiation mechanism, based on strong inhibitory output signals from the BG to the FEF and SC. We investigated the STN and CD (BG input), and the SNr (BG oculomotor output) to examine changes across the BG network. This revealed robust task-contingent shifts in BG signaling (Chapter 3), which uniquely impacted saccade initiation according to behavioral condition (Chapters 3 and 4). The thesis concludes with a published short review of the mechanistic effects of BG deep brain stimulation (Chapter 5), and a general discussion including proof of concept saccade behavioral changes in an MPTP-induced Parkinsonian model (Chapter 6). The studies presented here demonstrate that the conditions for saccade initiation by the FEF and SC vary according to behavioral condition, while simultaneously, large-scale task dependent shifts occur in BG signaling consistent with the observed modulation of FEF and SC activity. Taken together, these describe a mechanistic framework by which the cortico-BG loop may contribute to the flexible control of behavior.