Molecular switch discovery could lead to new neurological therapies

The researchers looked at the role of the natural substance cholecystokinin (CCK) in modulating communication between cells in the brain. CCK, originally isolated from the digestive tract, is one of the most abundant small proteins, or peptides, in the brain, and it is linked to psychiatric disorders such as anxiety, depression, and schizophrenia.

The study appears as an Advanced Online Publication in Nature Neuroscience. Using sophisticated electrophysiological measurements, the UC Irvine team showed that CCK functions in the brain as an extremely specific switch with a highly unusual, dual action.

On the one hand, CCK enhances the synthesis and release of natural marijuana-like (endocannabinoid) substances from a particular class of nerve cells known to modulate neuronal excitability in brain circuits critical for cognition and mood. On the other hand, CCK robustly increases electrical activity in a different class of nerve cells that play critical roles in learning and memory.

“These results reveal a new mechanism for CCK to regulate nerve cell activity in a highly specific manner,” said Csaba Foldy, postdoctoral researcher in anatomy and neurobiology and lead author of the study.

The study looked at the hippocampus, the region of the brain involved in learning, memory and emotion. Damage or alterations to the hippocampus can cause cognitive disorders, epilepsy, and mental illness.

Ivan Soltesz, professor and chair of the Department of Anatomy and Neurobiology and senior author of the study, said: “This discovery offers the potential for new drug therapies because the link between CCK and cannabinoids can now be further investigated to determine how its modulation by either pharmacological or genetic means alters excitability in the hippocampus.”