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Publication : Excitability governs neural development in a hippocampal region-specific manner.

First Author  Johnson-Venkatesh EM Year  2015
Journal  Development Volume  142
Issue  22 Pages  3879-91
PubMed ID  26417041 Mgi Jnum  J:226695
Mgi Id  MGI:5698295 Doi  10.1242/dev.121202
Citation  Johnson-Venkatesh EM, et al. (2015) Excitability governs neural development in a hippocampal region-specific manner. Development 142(22):3879-91
abstractText  Neuronal activity, including intrinsic neuronal excitability and synaptic transmission, is an essential regulator of brain development. However, how the intrinsic neuronal excitability of distinct neurons affects their integration into developing circuits remains poorly understood. To investigate this problem, we created several transgenic mouse lines in which intrinsic excitability is suppressed, and the neurons are effectively silenced, in different excitatory neuronal populations of the hippocampus. Here we show that CA1, CA3 and dentate gyrus neurons each have unique responses to suppressed intrinsic excitability during circuit development. Silenced CA1 pyramidal neurons show altered spine development and synaptic transmission after postnatal day 15. By contrast, silenced CA3 pyramidal neurons seem to develop normally. Silenced dentate granule cells develop with input-specific decreases in spine density starting at postnatal day 11; however, a compensatory enhancement of neurotransmitter release onto these neurons maintains normal levels of synaptic activity. The synaptic changes in CA1 and dentate granule neurons are not observed when synaptic transmission, rather than intrinsic excitability, is blocked in these neurons. Thus, our results demonstrate a crucial role for intrinsic neuronal excitability in establishing hippocampal connectivity and reveal that neuronal development in each hippocampal region is distinctly regulated by excitability.
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