Abstract
Polycystins (PKD2, PKD2L1 and PKD2L2) are members of transient receptor potential (TRP) family, which form ciliary ion channels. Most notably, PKD2 dysregulation in the kidney is associated with polycystic kidney disease but the physiological role of PKD2L1 is largely undefined. In this report, we develop animal models to track the expression and subcellular localization of these channels in the brain. We discover PKD2L1 localizes and functions as a Ca2+ channel in the primary cilia of hippocampal neurons, which apically radiate from the axon hillock. Loss of PKD2L1 expression ablates primary cilia maturation, and attenuates neuronal high frequency excitability, and precipitates seizure susceptibility and autism spectrum disorder-like behavior in mice. The disproportionate impairment of interneuron excitability suggests circuit disinhibition underlies the neurophenotypic features of these mice. Our results identify PKD2L1 channels as regulators of hippocampal excitability and the neuronal primary cilia as organelle mediators of brain electrical signaling.
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