Cholecystokinin Modulates Corticostriatal Transmission and Plasticity in Rodents

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Neuropeptide Signaling

Background:

• Cholecystokinin (CCK) is recognized as a crucial neuropeptide involved in synaptic plasticity and memory.
• Its role in the striatum, essential for motor control, remains largely unexplored despite its abundance in basal ganglia.

Purpose of the Study:

• To investigate the role of CCK in modulating striatal medium spiny neuron (MSN) membrane properties.
• To examine CCK's influence on synaptic transmission and plasticity between the secondary somatosensory cortex (S2) and MSNs in rodents.

Main Methods:

• In vivo optopatch-clamp recordings in mice to assess CCK receptor Type 2 (CCK2R) antagonist effects on corticostriatal transmission.
• Ex vivo rat preparation to analyze CCK2R inhibition's impact on MSN membrane properties and synaptic plasticity.

Main Results:

• CCK2R antagonists decreased corticostriatal transmission in both direct and indirect pathway MSNs.
• CCK2R inhibition increased MSN excitability by reducing spike threshold and rheobase.
• CCK2R blockade shifted spike-timing-dependent plasticity from long-term potentiation to long-term depression.

Conclusions:

• CCK, primarily through CCK2R, significantly modulates corticostriatal transmission and MSN excitability.
• This research provides novel insights into striatal function and plasticity, highlighting CCK's potential relevance to basal ganglia disorders.