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 study this question, 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 P15. In contrast, silenced CA3 pyramidal neurons appear to develop normally. Silenced dentate granule cells develop with input specific decreases in spine density starting at P11; yet, 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 critical role for intrinsic neuronal excitability in establishing hippocampal connectivity and reveal that neuronal development in each hippocampal region is distinctly regulated by excitability.
- Received January 7, 2015.
- Accepted September 10, 2015.