Juan Bacigalupo, PhD — University of Chile

In vitro coherent network activity – an electrophysiological model for drug testing in the mouse model of fragile X
Juan Bacigalupo

with Carlos Maureira, PhD, Postdoctoral Fellow

FRAXA Awards:
$45,000 in 2012
$45,000 in 2011

One test for any potential drug therapy for fragile X syndrome is whether it can restore normal function to a network of neurons. Specific patterns of abnormal activity have been found in these networks in fragile X mouse brain. This system may prove to be a quick and efficient way of screening possible therapeutics.

Spontaneous and event-driven activity in a neuronal network strongly depends on intrinsic cellular properties, synaptic connections and network topological features. Relevant dynamics of neuronal activity within the network results from the coordinated discharge of large groups of neurons; within these groups, some their components form specific functional assembles displaying normal or anomalous activity patterns, influenced by intrinsic, synaptic and network properties. Network patterns or states of activity significantly affect sensory and endogenous neuronal activity and behaviors.

The mutually interacting factors – intrinsic, synaptic and network properties- make coherent network activity highly sensitive to small perturbations and influences, as for example, ephaptic interactions. Small influences may be amplified, leading to new dominant states of activity or even to extinguish spontaneous normal activity.

We have found abnormal network activity patters in Fragile X mouse brain slices. In the Fragile X syndrome, abnormal network dynamics might interfere with the formation of neuronal assembles, precluding normal representations and neuronal computation capabilities. Our aim is to relate the anomalous network dynamics of the mutant brain slices to its underlying intrinsic, synaptic and network characteristics. Additionally, we aim to establish network dynamics as a sensitive drug screening method for testing possible therapeutics strategies.