Brain Structure and Function

, Volume 225, Issue 1, pp 249–284 | Cite as

Cholecystokinin in the central nervous system of the sea lamprey Petromyzon marinus: precursor identification and neuroanatomical relationships with other neuronal signalling systems

  • D. Sobrido-Cameán
  • L. A. Yáñez-Guerra
  • D. Robledo
  • E. López-Varela
  • M. C. Rodicio
  • M. R. Elphick
  • R. Anadón
  • Antón Barreiro-IglesiasEmail author
Original Article


Cholecystokinin (CCK) is a neuropeptide that modulates processes such as digestion, satiety, and anxiety. CCK-type peptides have been characterized in jawed vertebrates and invertebrates, but little is known about CCK-type signalling in the most ancient group of vertebrates, the agnathans. Here, we have cloned and sequenced a cDNA encoding a sea lamprey (Petromyzon marinus L.) CCK-type precursor (PmCCK), which contains a CCK-type octapeptide sequence (PmCCK-8) that is highly similar to gnathostome CCKs. Using mRNA in situ hybridization, the distribution of PmCCK-expressing neurons was mapped in the CNS of P. marinus. This revealed PmCCK-expressing neurons in the hypothalamus, posterior tubercle, prethalamus, nucleus of the medial longitudinal fasciculus, midbrain tegmentum, isthmus, rhombencephalic reticular formation, and the putative nucleus of the solitary tract. Some PmCCK-expressing neuronal populations were only observed in adults, revealing important differences with larvae. We generated an antiserum to PmCCK-8 to enable immunohistochemical analysis of CCK expression, which revealed that GABA or glutamate, but not serotonin, tyrosine hydroxylase or neuropeptide Y, is co-expressed in some PmCCK-8-immunoreactive (ir) neurons. Importantly, this is the first demonstration of co-localization of GABA and CCK in neurons of a non-mammalian vertebrate. We also characterized extensive cholecystokinergic fibre systems of the CNS, including innervation of habenular subnuclei. A conspicuous PmCCK-8-ir tract ascending in the lateral rhombencephalon selectively innervates a glutamatergic population in the dorsal isthmic grey. Interestingly, this tract is reminiscent of the secondary gustatory/visceral tract of teleosts. In conclusion, this study provides important new information on the evolution of the cholecystokinergic system in vertebrates.


Lamprey Cholecystokinin GABA Glutamate Brain Spinal cord 





Anterior lateral line nerve


Anterior rhombencephalic reticular nucleus


Rhombencephalic Müller cell 3


Optic chiasm


Dorsal cell


Dorsal column


Dorsal column nucleus


Dorsal hypothalamus


Dorsal isthmic commissure


Dorsal isthmic grey


Dorsal nucleus of the octavolateralis area


Descending trigeminal root


Prethalamic eminence


Fasciculus retroflexus


Gamma-aminobutyric acid


Glomerular layer of olfactory bulb








Giant isthmic neuron


Oculomotor nucleus, dorsal subnucleus


Oculomotor nucleus, lateral subnucleus


Interpeduncular nucleus




Dorsal isthmus region


Ventral isthmus region


Trochlear nucleus


Glossopharyngeal motor nucleus


Left habenula


Lateral hypothalamus


Lateral pallium


Lateral pallium, dorsal part


Lateral pallium, ventral part


Lamina terminalis




Giant Müller cells 1–3


Nucleus M5 of Schober


Mammillary nucleus


Medial longitudinal fasciculus


Medial nucleus of the octavolateralis area


Medial pallium


Mammillary recess


Medial rhombencephalic reticular nucleus


Mauthner neuron




Nucleus of the medial longitudinal fasciculus


Olfactory bulb


Octavolateralis area


Octavomotor anterior nucleus


Optic nerve


Optic tectum


Optic tract


Pineal organ


Posterior commissure


Choroid plexus


Posterior lateral line nerve


Petromyzon marinus


Preoptic nucleus


Nucleus of the postoptic commissure


Postoptic recess


Perioculomotor region


Posterior rhombencephalic reticular nucleus






Posterior tubercle nucleus




Right habenula


Neurobiotin labelling from the spinal cord


Neuropeptide Y


Spinal cord


Subhippocampal lobe


Sulcus limitans


Nucleus of the solitary tract


Spino‐occipital motor column






Tyrosine hydroxylase




Torus semicircularis




Facial motor nucleus


Octaval nerve


Ventral hypothalamus


Trigeminal motor nucleus


Ventral nucleus of the octavolateralis area


Trigeminal spinal nucleus


Vagal motor nucleus


Zona limitans intrathalamica



Grant sponsors: Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund 2007–2013 (Grant number: BFU-2017-87079-P). L.A.Y.G was supported by a PhD studentship awarded by the Mexican Council of Science and Technology (CONACyT studentship no. 418612) and Queen Mary University of London. D.R. is supported by Institute Strategic Funding Grants to The Roslin Institute (BBS/E/D/20002172, BBS/E/D/30002275 and BBS/E/D/10002070). The authors thank the staff of Ximonde Biological Station for providing the lampreys used in this study, and the Microscopy Service (University of Santiago de Compostela) and Dr. Mercedes Rivas Cascallar for confocal microscope facilities and help.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest (financial or non-financial).

Ethical standards

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

429_2019_1999_MOESM1_ESM.pdf (74 kb)
Supplementary Figure 1. Alignment of selected CCK precursors from chordates used for construction of the phylogenetic tree in figure 1. Conserved residues are highlighted. Conservation in more than 70% of sequences is highlighted in black, conservative substitutions are highlighted in grey. Species names and accession numbers are as follows: Hsap (Homo sapiens; P06307), Rnor (Rattus norvegicus; P01355), Sscr (Sus scrofa; P01356), Ggal (Gallus gallus; Q9PU41), Cpic (Chrysemys picta belli; XP_005278641.1, XP_005278642.1), Amis (Alligator mississippiensis; KYO43311.1), Lcha (Latimeria chalumnae; XP_006013099.1), Ipun (Ictalurus punctatus; XM_017484277.1), Amex (Astyanax mexicanus; XP_022531953.1), Drer (Danio rerio; XP_002665661.2), Saca (Squalus acanthias; CAB10585.1), Cmil (Callorhinchus milii; XP_007895078.1), Pmar (P. marinus; ADJ57604.1), Lcam (Lethenteron camtschaticum; APJL01044986.1), Cint (Ciona intestinalis; NP_001027711.1) (PDF 74 kb)


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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Functional Biology, Edificio CIBUS, Campus Vida, Faculty of BiologyUniversidade de Santiago de CompostelaSantiago de CompostelaSpain
  2. 2.School of Biological and Chemical SciencesQueen Mary University of LondonLondonUK
  3. 3.The Roslin Institute and Royal (Dick) School of Veterinary StudiesThe University of EdinburghMidlothianUK

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