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Monoallelic deletion of the microRNA biogenesis gene Dgcr8 produces deficits in the development of excitatory synaptic transmission in the prefrontal cortex.

Neural development | Apr 5, 2011

BACKGROUND: Neuronal phenotypes associated with hemizygosity of individual genes within the 22q11.2 deletion syndrome locus hold potential towards understanding the pathogenesis of schizophrenia and autism. Included among these genes is Dgcr8, which encodes an RNA-binding protein required for microRNA biogenesis. Dgcr8 haploinsufficient mice (Dgcr8+/-) have reduced expression of microRNAs in brain and display cognitive deficits, but how microRNA deficiency affects the development and function of neurons in the cerebral cortex is not fully understood. RESULTS: In this study, we show that Dgcr8+/- mice display reduced expression of a subset of microRNAs in the prefrontal cortex, a deficit that emerges over postnatal development. Layer V pyramidal neurons in the medial prefrontal cortex of Dgcr8+/- mice have altered electrical properties, decreased complexity of basal dendrites, and reduced excitatory synaptic transmission. CONCLUSIONS: These findings demonstrate that precise microRNA expression is critical for the postnatal development of prefrontal cortical circuitry. Similar defects in neuronal maturation resulting from microRNA deficiency could represent endophenotypes of certain neuropsychiatric diseases of developmental onset.

Pubmed ID: 21466685 RIS Download

Mesh terms: Animals | Brain | Dendrites | Electrophysiological Phenomena | Excitatory Postsynaptic Potentials | Image Processing, Computer-Assisted | Mice | Mice, Inbred C57BL | Mice, Transgenic | MicroRNAs | Neurons | Patch-Clamp Techniques | Prefrontal Cortex | Proteins | Pyramidal Cells | RNA-Binding Proteins | Reverse Transcriptase Polymerase Chain Reaction | Synaptic Transmission