Optogenetic stimulation effectively enhances intrinsically generated network synchrony

Ahmed El Hady,Ghazaleh Afshar,Kai Bröking,Walter Stühmer,Theo Geisel,Fred Wolf,Oliver M Schlüter

doi:10.3389/fncir.2013.00167

Abstract

Synchronized bursting is found in many brain areas and has also been implicated in the pathophysiology of neuropsychiatric disorders such as epilepsy, Parkinson’s disease, and schizophrenia. Despite extensive studies of network burst synchronization, it is insufficiently understood how this type of network wide synchronization can be strengthened, reduced, or even abolished. We combined electrical recording using multi-electrode array with optical stimulation of cultured channelrhodopsin-2 transducted hippocampal neurons to study and manipulate network burst synchronization. We found low frequency photo-stimulation protocols that are sufficient to induce potentiation of network bursting, modifying bursting dynamics, and increasing interneuronal synchronization. Surprisingly, slowly fading-in light stimulation, which substantially delayed and reduced light-driven spiking, was at least as effective in reorganizing network dynamics as much stronger pulsed light stimulation. Our study shows that mild stimulation protocols that do not enforce particular activity patterns onto the network can be highly effective inducers of network-level plasticity.

Highlights

Regular highly synchronized bursting in vivo has been observed in hippocampus (Kandel and Spencer, 1961), visual cortex (Cattaneo et al, 1981; Martinez-Conde et al, 2000), and lateral geniculate nucleus (Reinagel et al, 1999)
We found that wholefield light stimulation of channelrhodopsin-2 transducted neuronal networks induced a change in the bursting dynamics of the network
Both the average normalized burst occurrence rate (BR) (n = 10 experiments) and the average normalized intra-burst firing rate (IBFR) significantly increased by 36 and 15%, respectively, after stimulation. These results indicate that the observed change in the network dynamics is both amino-3-hydroxy-5-methyl4-isoxazolepropionic acid (AMPA)- and NMDAdependent

Summary

Introduction

Regular highly synchronized bursting in vivo has been observed in hippocampus (Kandel and Spencer, 1961), visual cortex (Cattaneo et al, 1981; Martinez-Conde et al, 2000), and lateral geniculate nucleus (Reinagel et al, 1999). Bursting has been implicated in the development of neural circuits in visual system (Rochefort et al, 2009), in barrel cortex (Minlebaev et al, 2009), and in hippocampus (Leinekugel et al, 2002). In vitro pyramidal neuron bursting underlies population synchrony in hippocampal and cortical slices (Miles et al, 1988; Silva et al, 1991; Van Drongelen et al, 2003). Neuronal network bursting and synchronization have clinical implications. There are diseases where a lack of neural synchrony affects cognitive function as has been argued in the case of schizophrenia (Uhlhaas and Singer, 2010)

Methods

Results

Conclusion