Mapping CCK-producing neurons in the sea lamprey — one of the oldest living vertebrates — reveals that this gut-brain peptide system has been conserved for over 500 million years of evolution.
500+ million yearsCCK peptide structure has been conserved from ancient jawless fish to modern humans — one of the longest-running signaling systems in vertebrate evolution
What the researchers found
The sea lamprey CCK-8 peptide is highly similar to mammalian CCK, with CCK neurons distributed across hypothalamus, midbrain, and brainstem regions, and showing the first documented GABA-CCK co-localization in a non-mammalian vertebrate.
Why it matters
Understanding CCK in the most ancient vertebrates reveals which aspects of this gut-brain signaling system are fundamental to all vertebrates, providing evolutionary context for how CCK regulates appetite, digestion, and mood in humans.
The numbers in context
8+ brain regions with CCK neurons; first GABA/CCK co-localization in non-mammal; adult-specific populations
How the study worked
cDNA cloning and sequencing, mRNA in situ hybridization for neuron mapping, custom antiserum generation for immunohistochemistry, and co-localization studies with GABA, glutamate, serotonin, tyrosine hydroxylase, and neuropeptide Y.
Who was studied
Sea lampreys (Petromyzon marinus), adults and larvae
What this study cannot tell us
Study is limited to neuroanatomical mapping in one species and does not test CCK function in the lamprey. Differences between larval and adult expression patterns complicate interpretation. Findings may not directly translate to understanding CCK function in mammals.
How to read the evidence
Rated moderate because the study uses rigorous neuroanatomical and molecular techniques with comprehensive brain mapping, though it is descriptive rather than functional.
When this study was published
Published in 2020, this study provides foundational evolutionary data about CCK signaling that remains relevant for understanding neuropeptide evolution.
The bigger picture
The deep conservation of CCK signaling from lampreys to humans suggests this peptide plays such a fundamental role in vertebrate biology that evolution has preserved it largely unchanged for over half a billion years, underscoring its importance in gut-brain communication.
Questions still open
- What functional role does GABA-CCK co-expression play in lamprey neurons, and is this co-localization functionally equivalent to mammalian systems?
- Does lamprey CCK regulate feeding behavior the same way it does in mammals?
- How did CCK signaling diversify as vertebrates evolved jaws and more complex nervous systems?
Common questions
What is the sea lamprey and why study its brain?
What is CCK and why does its presence in lampreys matter?
Read the original research
Cholecystokinin in the central nervous system of the sea lamprey Petromyzon marinus: precursor identification and neuroanatomical relationships with other neuronal signalling systems.
Brain structure & function, 225(1), 249-284
Citation
Sobrido-Cameán, D; Yáñez-Guerra, L A; Robledo, D; López-Varela, E; Rodicio, M C; Elphick, M R; Anadón, R; Barreiro-Iglesias, Antón. (2020). Cholecystokinin in the central nervous system of the sea lamprey Petromyzon marinus: precursor identification and neuroanatomical relationships with other neuronal signalling systems.. Brain structure & function, 225(1), 249-284. https://doi.org/10.1007/s00429-019-01999-2