The isolation, characterization, and bioactivity in the feeding circuitry o
f a novel neuropeptide in the Aplysia californica central nervous system ar
e reported. The 17-residue amidated peptide, NGGTADALYNLPDLEKlamide, has be
en termed cerebrin due to its primary location in the cerebral ganglion. Li
quid chromatographic purification guided by matrix-assisted laser desorptio
n/ionization time-of-flight mass spectrometry allowed the isolation of the
peptide with purity adequate for Edman sequencing. The cerebrin cDNA has be
en characterized and encodes an 86 amino acid prohormone that predicts cere
brin and one additional peptide. Mapping using in situ hybridization and im
munocytochemistry showed that cerebrin containing neuronal somata are local
ized almost exclusively in the cerebral ganglion, mostly in the F- and C-cl
usters. Both immunostaining and mass spectrometry demonstrated the presence
of cerebrin in the neurohemal region of the upper labial nerve. In additio
n, immunoreactive processes were detected in the neuropil of all of the gan
glia, including the buccal ganglia, and in some interganglionic connectives
, including the cerebral-buccal connective. This suggests that cerebrin may
also function as a local signaling molecule. Cerebrin has a profound effec
t on the feeding motor pattern elicited by the command-like neuron CBI-2, d
ramatically shortening the duration of the radula protraction in a concentr
ation-dependent manner, mimicking the motor-pattern alterations observed in
food induced arousal states. These findings suggest that cerebrin may cont
ribute to food-induced arousal in the animal. Cerebrin-like immunoreactivit
y is also present in Lymnaea stagnalis suggesting that cerebrin-like peptid
es may be widespread throughout gastropoda.