Nitric oxide feedback to ciliary photoreceptor cells gates a UV avoidance circuit

Neuronal Circuits Conference
March 21, 2024

Gáspár Jékely

Centre for Organismal Studies, Heidelberg University

Mastodon: @jekely@biologists.social

Phylogeny of Metazoa and diversity of nervous systems

Platynereis dumerilii







  • breeding culture, full life-cycle
  • embryos daily, year round
  • genome sequence
  • microinjection, transgenesis
  • neuron-specific promoters and antibodies
  • knock-out lines
  • neuronal connectome
  • whole-body neuronal activity imaging
  • whole-animal pharmacology by bath application 😎

Platynereis dumerilii















Spawning
movie by Albrecht Fischer


Synchronously developing larvae

UV response in Platynereis larvae

UV response in Platynereis larvae

Brain ciliary photoreceptors with ramified cilia




Ciliary photoreceptors express a UV opsin, c-opsin1

Reduced ciliary compartment in c-opsin1 mutants

UV avoidance is dependent on c-opsin1

Whole-body volume EM of an entire three-day-old larva


Synaptic connectome

Head neuropils and connectivity

Circuitry of ciliary photoreceptors




Circuitry of ciliary photoreceptors


Serotonergic neurons to activate cilia

Ser-h1 neurons, EM reconstruction

Strong cPRC activation after UV exposure

UV response is c-opsin1-dependent

Nitric-oxide synthase in postsynaptic interneurons



      HCR             Transgenic labelling         immunostaining

NO is produced in the neuropil after UV stimulation

NOS mutants have altered cPRC response

NOS mutants have altered INRGW response

Ciliary response to UV in wt and NOS mutants







ciliary beat frequency







Swimming speed

NOS mutants show defective UV avoidance



NO signal is short-range

NOS protein in the INNOS dendritic compartment

Two unusual guanylyl cyclases in the cPRCs

NIT-GC1 RNA
NIT-GC1 protein
NIT-GC2 RNA
NIT-GC2 protein

Two unusual guanylyl cyclases in the cPRCs

NIT-GC1 producs cGMP upon NO addition

NIT-GC1 mediates NO-feedback




anti-NIT-GC1 immuno




NIT-GC2 mediates phototransduction




anti-NIT-GC2 immuno

Mathematical modelling of the circuit

Model fitting

wild type
NOS-11
NOS-23
NIT-GC2 mo.

Integration and memory of UV exposure

Synaptic+chemical connectomes -> circuit dynamics and function

Acknowledgements

Heidelberg

  • Alexandra Kerbl
  • Sanja Jasek
  • Emily Savage
  • Benedikt Dürr
  • Simone Wolters
  • Lara Keweloh
  • Kevin Urbansky

  • Suat Özbek
  • Maike Fath
  • Ibrahim Akhtar

Exeter

  • Kei Jokura
  • Emelie Brodrick
  • Luis A. Bezares-Calderón
  • Luis Yanez
  • Victoria Moris
  • Daniel Thiel
  • Adam Johnstone