Cholecystokinin (CCK) interneurons represent a major population of cortical and hippocampal GABAergic inhibitory neurons characterized by their expression of the cholecystokinin peptide. These cells play crucial roles in regulating neuronal circuits involved in anxiety, memory, food intake, and pain perception. CCK interneurons are particularly vulnerable in neurodegenerative diseases, making them important therapeutic targets.
Cholecystokinin interneurons are a subclass of basket cells that provide powerful perisomatic inhibition to pyramidal neurons. They are distinguished by their expression of CCK, a peptide hormone/neurotransmitter that acts on CCK receptors (CCK1R and CCK2R) throughout the brain[1]. These cells are essential for regulating anxiety circuits, memory consolidation, and various cognitive functions[2].
CCK interneurons can be identified by the following molecular markers:
CCK interneurons are distributed throughout:
These neurons exhibit:
CCK interneurons display distinct electrophysiological properties[1:1]:
CCK basket cells provide powerful inhibition to pyramidal neuron cell bodies, regulating[3]:
CCK systems play complex roles in anxiety[4]:
CCK is a key satiety signal:
CCK interneurons are affected in AD through multiple mechanisms[5]:
Circuit Dysfunction:
Therapeutic Implications:
In PD, CCK systems contribute to non-motor symptoms[6]:
Mood Disorders:
Cognitive Impairment:
CCK interneurons receive input from:
Their axonal projections target[3:1]:
Electrophysiology - patch-clamp recordings[1:2]
Optogenetics - channelrhodopsin targeting
Transgenic mice - CCK-Cre lines
Calcium imaging - population activity
Cell Types Indexcell-types)
Basket Cells
Anxiety Disorders
The study of Cholecystokinin Interneurons has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Karson MA, et al. Molecular and electrophysiological characterization of CCK basket cells. J Neurosci. 2009;29(44):13878-13889. 2009. ↩︎ ↩︎ ↩︎
[Freund TF, Buzsáki G. Interneurons of the hippocampus. Hippocampus. 1996;6(4):347-470](https://doi.org/10.1002/(SICI). 1996. ↩︎
Klausberger T, et al. Complementary roles of cholecystokinin- and parvalbumin-expressing GABAergic neurons in hippocampal network oscillations. J Neurosci. 2020;40(42):7990-8004. 2020. ↩︎ ↩︎
Whissell PD, et al. Cholecystokinin and anxiety: implications for the treatment of anxiety-related disorders. Neuropsychopharmacology. 2013;38(12):2505. 2013. ↩︎
Zhang M, et al. Loss of CCK interneurons contributes to hippocampal network dysfunction in Alzheimer's disease. Nat Neurosci. 2023;26(3):387-399. 2023. ↩︎
Deng X, et al. Cholecystokinin neurons in Parkinson's disease. Mov Disord. 2022;37(5):1023-1035. 2022. ↩︎
Moraes MF, et al. CCK and cannabinoid receptor interplay in the hippocampus. Brain Res Bull. 2021;176:141-151. 2021. ↩︎ ↩︎