RT Journal Article
SR Electronic
T1 A serotonergic axon-cilium synapse drives nuclear signaling to maintain chromatin accessibility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.27.461878
DO 10.1101/2021.09.27.461878
A1 Shu-Hsien Sheu
A1 Srigokul Upadhyayula
A1 Vincent Dupuy
A1 Song Pang
A1 Andrew L. Lemire
A1 Deepika Walpita
A1 H. Amalia Pasolli
A1 Fei Deng
A1 Jinxia Wan
A1 Lihua Wang
A1 Justin Houser
A1 Silvia Sanchez-Martinez
A1 Sebastian E. Brauchi
A1 Sambashiva Banala
A1 Melanie Freeman
A1 C. Shan Xu
A1 Tom Kirchhausen
A1 Harald F. Hess
A1 Luke Lavis
A1 Yu-Long Li
A1 Séverine Chaumont-Dubel
A1 David E. Clapham
YR 2021
UL http://biorxiv.org/content/early/2021/09/28/2021.09.27.461878.abstract
AB Chemical synapses between axons and dendrites mediate much of the brain’s intercellular communication. Here we describe a new kind of synapse – the axo-ciliary synapse - between axons and primary cilia. By employing enhanced focused ion beam – scanning electron microscopy on samples with optimally preserved ultrastructure, we discovered synapses between the serotonergic axons arising from the brainstem, and the primary cilia of hippocampal CA1 pyramidal neurons. Functionally, these cilia are enriched in a ciliary-restricted serotonin receptor, 5-hydroxytryptamine receptor 6 (HTR6), whose mutation is associated with learning and memory defects. Using a newly developed cilia-targeted serotonin sensor, we show that optogenetic stimulation of serotonergic axons results in serotonin release onto cilia. Ciliary HTR6 stimulation activates a non-canonical Gαq/11-RhoA pathway. Ablation of this pathway results in nuclear actin and chromatin accessibility changes in CA1 pyramidal neurons. Axo-ciliary synapses serve as a distinct mechanism for neuromodulators to program neuron transcription through privileged access to the nuclear compartment.Competing Interest StatementThe authors have declared no competing interest.