The actions of cholecystokinin and related peptides on pyramidal neurones of the mammalian hippocampus.

The presence of cholecystokinin octapeptide (CCK-8) immunoreactivity in the vicinity of the pyramidal neurones of the mammalian hippocampus has allowed us to investigate the central postsynaptic actions of CCK-8 and a number of related peptides, at a site thought to be innervated by a peptidergic pathway. Intracellular records from pyramidal cells of the CA1 region of the hippocampal slice preparation were used to determine changes in excitability and associated changes in membrane potential and resistance evoked by the pressure application of peptides into the cell body layer, from an independently mounted multibarrelled micropipette. The tetra- and octa-peptide C-terminal fragments of cholecystokinin evoked abrupt and rapidly reversible depolarizations which were accompanied by marked increases in excitability and a decrease in membrane input resistance. A comparison was made of the actions of these peptides with those of glutamate, released by iontophoresis from an adjacent barrel of the same multibarrelled pipette. The rate of onset of the cholecystokinin-evoked response was similar to that of the response evoked by glutamate. C-terminal fragments of gastrin (G-13 and G-14) and bombesin were also found to be excitatory to pyramidal neurones in the CA1 region. However, the nonsulphated form of CCK-8 was inactive, as was substance P, a peptide not present in the hippocampus.