Systems NeuroscienceResearch PaperAltered synchrony and connectivity in neuronal networks expressing an autism-related mutation of neuroligin 3
Section snippets
Primary cell culture
Dissociated primary co-cultures of neurons and glia were grown on p-type, 12 Ω/cm, boron-doped, double-side polished, 1 cm2 pre-cut silicon wafers, 1 mm in thickness (Silicon Quest International, Reno, NV, USA) as described (Goda and Colicos, 2006). Wafers were treated with poly-d-lysine (Sigma-Aldrich, St. Louis) (50 μg/ml working dilution) overnight. Wafers were then washed in PBS 3×10 min and incubated for 3 h with mouse laminin (Sigma-Aldrich) at a final concentration of 10 μg/ml.
Recording of spontaneous network activity
Correlated spatiotemporal activity patterns of neuronal networks are suggested to be important for reliable transmission, processing and storage of information (Madhavan et al 2007, Xu and Clancy 2008). To investigate the role of NL3 in neuronal connectivity we compared the spontaneous activity patterns of networks containing cells overexpressing wild type or mutant NL3. Network activity was monitored by recording intracellular calcium (Ca2+) of neurons using the fluorescent Ca2+ sensitive dye
Discussion
Biochemical studies as well as postmortem and genetic data have provided important insights into the underlying molecular basis of ASD. However autism presents as a cognitive disorder, there are currently few functional or systems-level paradigms to assess how specific biochemical pathways affect activity patterns, and consequently information processing, in the brain. Addressing this in a model system has been difficult, for example, results collected from NL3 knockout mice suggest there is no
Acknowledgments
We thank Robyn Flynn for comments on the manuscript and Lucas Scott for technical assistance. This work was supported by CIHR and Cure Autism Now grants to M.C. M.C. is an AHFMR Scholar and an HSFC Investigator. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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