Abstract
Primary cilia are known to play essential signaling roles in nearly every cell in the human body, including neural subtypes. Decades of research have shown that cilia function is critical for neurogenesis and cortical formation during embryonic development. Intriguingly, although neuronal cilia are maintained throughout the life of an animal, their contributions to postnatal brain function remain unclear. Mutations in cilia genes or impairments to cilia structure cause pleiotropic disorders in humans that manifest with developmental abnormalities and cognitive deficits. Recently, additional neuropsychiatric disorders and neurodegenerative diseases have been linked to ciliary dysfunction. Here, we present evidence that cilia-mediated signaling dynamically regulates excitatory synaptic properties. We find that acute disruption of cilia in postnatal excitatory pyramidal neurons leads to increased excitatory synaptic strengths and numbers. We characterize the expression of the cilia-localized neuropeptide receptor SSTR3, and find its expression is nearly exclusive to excitatory neurons in the postnatal visual cortex of rats. Finally, we report that the activation state of SSTR3 bidirectionally modulates excitatory synaptic strengths of excitatory neurons in vitro. This work proposes that primary cilia provide extrasynaptic modulation of neuronal excitability in the postnatal cortex, and may provide insights into the molecular underpinnings of neuronal disorders.