Synaptic plasticity and morphogenesis in the developing postnatal cerebral cortex

Learning how neurons interact, to create functional circuits, is crucial for understanding the basis of cognition and for shedding insight into the underpinnings of neurological disorders. This work will describe how changes in (1) postsynaptic N-methyl D-aspartate receptor (NMDAR) subunit composition and (2) dendritic spine morphology, influence synaptic transmission and synaptic plasticity in the developing cerebral cortex. Synaptic NMDARs undergo a dramatic activity-dependent change in subunit composition, going from being primarily NR2B-containing, to being increasingly NR2A-containing. Interestingly, this change in synaptic subunit composition correlates with developmental changes in the properties of synaptic plasticity. Using pharmacology, I have elucidated how NR2A- and NR2B-type NMDARs contribute to synaptic plasticity at distinct developmental time points. Using this approach, I demonstrate that the degree of NMDAR activation required for the induction of long term potentiation (LTP) increases with age. This work also focuses on the role of slit-robo GTPase activating protein 2 (srGAP2) on shaping the morphology of postsynaptic specializations, called dendritic spines. While the significance of dendritic spines is highly contentious, it has been shown that they play an important role in modulating the efficacy of glutamatergic synapses. This work demonstrates that srGAP2 is expressed at the synapse and that it has the ability to induce an elongation of dendritic spine shape, through the synergistic action of both its FBAR and RhoGAP domains. From a physiological perspective, srGAP2 also influences synaptic transmission, by altering the shape and the complement of receptors at the postsynaptic membrane. As a whole, this doctoral work highlights the importance of changes in postsynaptic receptor composition and dendritic spine morphology, in shaping neural circuitry

NMDA Receptor Antagonists Reveal Age-Dependent Differences in the Properties of Visual Cortical Plasticity

The suggestion that NMDA receptor (NMDAR)-dependent plasticity is subunit specific, with NR2B-types required for long-term depression (LTD) and NR2A-types critical for the induction of long-term potentiation (LTP), has generated much attention and considerable debate. By investigating the suggested subunit-specific roles of NMDARs in the mouse primary visual cortex over development, we report several important findings that clarify the roles of NMDAR subtypes in synaptic plasticity. We observed that LTD was not attenuated by application of ifenprodil, an NR2B-type antagonist, or NVP-AAM007, a less selective NR2A-type antagonist. However, we were surprised that NVP-AAM007 completely blocked adult LTP (postnatal day (P) 45–90), while only modestly affecting juvenile LTP (P21-28). To assess whether this developmental transition reflected an increasing role for NR2A-type receptors with maturity, we characterized the specificity of NVP-AAM007. We found not only that NVP-AAM007 lacks discernable subunit specificity but also that the effects of NVP-AAM077 on LTP could be mimicked using subsaturating concentrations of APV, a global NMDAR antagonist. These results indicate that the effects of NVP-AAM077 on synaptic plasticity are largely explained by nonspecific blockade of NMDARs. Moreover our findings are the first to reveal a developmental increase in the sensitivity of LTP to NMDAR antagonism. We suggest that discrepant reports describing the effect of NVP-AAM077 on LTP may be partially explained by this developmental shift in the properties of LTP. These results indicate that the degree of NMDAR activation required for LTP increases with development, providing insight into a novel underlying mechanism governing the properties of synaptic plasticity

Gestión Comercial - AM107 - 202101

El curso de Gestión Comercial es un cuso de carácter teórico-práctico dirigido a los estudiantes de 7mo ciclo, brinda al alumno los conceptos claves detrás de la gestión comercial y la administración de la fuerza de ventas. Durante el curso se revisan los temas básicos y las herramientas fundamentales de la gestión de ventas de una empresa. El alumno conocerá cuál es la relevancia del área de ventas en una empresa y qué desafíos existen en el día a día. El alumno también reconocerá la estructurar de un área de ventas en base al tipo de producto o servicio que vende, para luego asignar un perfil de vendedor correcto. Finalmente, se aprenderá acerca de los aspectos de reclutamiento, selección, entrenamiento, pronósticos y gestión de un área comercial. Propósito El curso de Gestión Comercial desarrolla la competencia general de Pensamiento Innovador y Pensamiento Critico, ambos a nivel 2, dado que, se resuelve problemas específicos del área comercial en base a una buena solución y aplicación de los fundamentos de la gestión comercial