Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons
- Brandeis University, United States
Abstract
Primary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured rat neocortical pyramidal neurons, and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to excitatory neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses, and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for all relevant figures.
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Author details
Funding
National Institute of General Medical Sciences (R35 GM122463)
- Piali Sengupta
National Institute of Mental Health (R21 MH118464)
- Gina G Turrigiano
- Piali Sengupta
National Institute of Neurological Disorders and Stroke (R35 NS111562)
- Gina G Turrigiano
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental procedures were approved by the the Brandeis University IACUC (IACUC protocol # 18002) and were performed according to NIH guidelines.
Copyright
© 2021, Tereshko et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons
eLife 10:e65427.
https://doi.org/10.7554/eLife.65427
