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Cholecystokininergic signaling exerts major control on cortico-striatal synaptic plasticity


The global obesity epidemic, a major public health issue, is the direct consequence of a deregulated food consumption. The first moments of life (DOHAD) would represent a critical window for the development of inappropriate eating habits during which the brain circuits controlling food intake could malfunction and lead to obesogenic behaviors later in life. In this context, our recent studies have shown that an unbalanced perinatal diet altered food preferences for fat and sweetness. This phenotype was associated with important reorganizations of the brain circuits controlling food intake, especially in the NAc and striatum. In these animals, the cholecystokinin receptor gene (CCK2R) was highly overexpressed. Does CCK, through this specific receptor, play a role in the appearance of the phenotype, in the reorganization of brain circuits underlying decision making and reward, and what is its role in brain plasticity? In addition to its well-known role as a satiety hormone, CCK also have (due to its very high presence in the brain) a major role largely unexplored on synaptic plasticity and memory, as suggested by a growing number of studies. In order to better understand the processes by which CCK impact plasticity, we chose to focus our attention on the striatum. This region presents a high level of plasticity and is part of the reward network which is crucial for the cognitive processes of motivation and appreciation, two major components of the feeding process. In our study, on horizontal slices of juvenile rat brains (P20-P35) we evaluated the impact of CCK2R (LY225910) and CCK1R (Lorglumide) antagonists on cortico-striatal plasticity by patch-clamp technique of MSNs using the most physiological synaptic plasticity induction protocol (STDP). This first part of our study shows that the CCK2R antagonist reverses sLTP synaptic plasticity (i.e. sLTD) and has no effect on sLTD. The CCK1R antagonist does not appear to have an effect on STDP. This first result unexpectedly indicates that CCK and its brain receptors CCK2R are essential for information processing coding in the cortico-striatal network. Further ex-vivo and in vivo experiments will allow us to better understand the involvement of this CCKergic signaling in the functioning of these brain circuits.
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hal-03271287 , version 1 (25-06-2021)


  • HAL Id : hal-03271287 , version 1


Chloe Guillaume, Patricia Parnet, Vincent Paillé. Cholecystokininergic signaling exerts major control on cortico-striatal synaptic plasticity. NeuroFrance 2021, May 2021, Strasbourg - à distance, France. . ⟨hal-03271287⟩
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