PTEN Loss Increases the Connectivity of Fast Synaptic Motifs and Functional Connectivity in a Developing Hippocampal Network.
作者： Caitlynn M. Barrows , Matthew P. McCabe , Hongmei Chen , John W. Swann , Matthew C. Weston
DOI: 10.1523/JNEUROSCI.0878-17.2017
关键词:
摘要: Changes in synaptic strength and connectivity are thought to be a major mechanism through which many gene variants cause neurological disease. Hyperactivation of the PI3K-mTOR signaling network, via loss function repressors such as PTEN, causes epilepsy humans animal models, altered mTOR may contribute broad range diseases. transmission have been reported models PTEN loss; however, full extent these changes, their effect on network function, is still unknown. To better understand scope we recorded from pairs mouse hippocampal neurons cultured two-neuron microcircuit configuration that allowed us characterize all four connection types within hippocampus. Loss caused changes excitatory inhibitory connectivity, were postsynaptic, presynaptic, transynsaptic, suggesting disruption has potential affect most circuit. Given complexity at level, measured behavior after deleting Pten an organotypic slice network. Slices containing -deleted showed increased recruitment into bursts. Importantly, not confined neurons, but involved entire extensive rewire way promotes widespread increase functional connectivity. SIGNIFICANCE STATEMENT Homozygous deletion neuronal subpopulations serves valuable model by hyperactivation. how deletions lead activity, investigated effects occur one week deletion. connections, including two forms inhibition inhibition, These data suggest single mutations diseases surprising types. Moreover, given robustness homeostatic plasticity, diverse necessary phenotypes synchrony.
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