[Todos] Seminarios conjuntos IFIBYNE-DFBMC- Lucas Pozzo-Miller- Viernes 15 de Julio 13 Hs.

[Paula Felman]

Viernes  15 de Julio 13 Hs. en el aula de seminarios.

Lucas Pozzo-Miller, Ph.D. Professor of Neurobiology.  The University 
of Alabama at Birmingham

Titulo: "BDNF Actions on both Sides of Synapses: TRPC Channels, MeCP2 
and the Cellular Neuropathology of Rett Syndrome"

Resumen: Dysfunctions of neuronal and network excitability have 
emerged as common features in disorders associated with intellectual 
disabilities, autism and seizure activity, all common clinical 
manifestations of Rett syndrome (RTT), a neurodevelopmental disorder 
caused by loss-of-function mutations in the transcriptional regulator 
MeCP2. I will discuss the consequences of Mecp2 mutation on 
hippocampal network excitability, as well as synapse structure and 
function evaluated with a combination of imaging and 
electrophysiological approaches in acute slices. Imaging the 
amplitude and spatiotemporal spread of neuronal depolarizations with 
voltage-sensitive dyes (VSD) revealed that the CA1 and CA3 regions of 
hippocampal slices from symptomatic male Mecp2 mutant mice are highly 
hyperexcitable. However, only the density of docked synaptic vesicles 
and the rate of release from the readily releasable pool are impaired 
in Mecp2 mutant mice, while synapse density and morphology are 
unaffected. The differences in network excitability were not observed 
in surgically isolated CA1 mini-slices, and blockade of GABAergic 
inhibition enhanced VSD signals to the same extent in Mecp2 mutant 
and wildtype mice, suggesting that network excitability originates in 
area CA3. Indeed, extracellular multi-unit recordings revealed a 
higher level of spontaneous firing of CA3 pyramidal neurons in slices 
from symptomatic Mecp2 mutant mice. The present results suggest that 
hyperactive CA3 pyramidal neurons contribute to hippocampal 
dysfunction and possibly to limbic seizures observed in Mecp2 mutant 
mice and RTT individuals.


Host: Veronica de la Fuente