Summary of the key research on CCK-driven neuronal homeostasis
| Process | Main findings | Brain region | References |
|---|---|---|---|
| Homeostatic plasticity (I): synaptic scaling | CCK colocalizes with glutamate neurons and controls glutamatergic excitatory projections and local GABAergic basket cells that gate signal flow and modulate network dynamics | Cortices, hippocampus, amígdala, ventral tegmental area | [62, 73, 74, 79, 80, 82, 83, 153] |
| CCK stimulates glutamate release and promotes long-term potentiation | Cortices, hippocampus, amygdala | [46–48, 81, 82, 120, 121] | |
| CCK shifts the plasticity of GABA synapses from long-term depression to long-term potentiation | Hipothalamus | [50] | |
| Homeostatic plasticity (II): intrinsic excitability | CCK-8 enhances acid-sensing ion channel currents in primary sensory neurons | Spinal cord | [130] |
| Endocannabinoid interactions | Coupling of CCKergic interneurons co-expressing CB1 receptors is involved in the generation and stability of rhythmic synchronous network activity of the hippocampal CA1 subfield | Hippocampus | [136] |
| CB1 and CCK2 receptors work together to modulate cortical GABAergic release in opposite ways | Cortex, periaqueductal grey | [80, 137] | |
| Neuroprotection | CCK triggers anti-oxidative stress pathway | Striatum, substantia nigra | [146] |
| CCK inactivates pro-inflammatory microglia response | Medial prefrontal cortex, caudate-putamen, hippocampus | [147] | |
| Dynamic neuromodulation of CCK release | Serotonin induces CCK release via 5-HT3R | Cortex, nucleus accumbens | [153] |
| GABA regulates CCK release | Cortex | [156] | |
| NMDA receptors promote CCK release | Cortex, hippocampus | [120, 121] | |
| Dopamine controls CCK release | Striatum | [157] | |
| Endogenous opioids mediate CCK release | Spinal cord, frontal cortex | [158, 159] |
CCK: cholecystokinin; CB1: cannabinoid type-1
SJB: Conceptualization, Investigation, Methodology, Validation, Writing—original draft, Writing—review & editing.
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Santiago J. Ballaz, who is the Guest Editor of Exploration of Drug Science, had no involvement in the decision-making or the review process of this manuscript.
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