Neural circuit mechanisms of the cholecystokinin (CCK) neuropeptide system in addiction

Ma, Yihe; Giardino, William J.

doi:10.1016/j.addicn.2022.100024

Cited by 15 publications

(8 citation statements)

References 83 publications

(80 reference statements)

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“…Remarkably, we find an important increase of CCK -expressing cells in human vs. mouse dorsal striatum, which might indicate its greater involvement in highly complex computational processes for motor and cognitive functions in the human. Little is known about the role of CCK -expressing cells in the central nervous system 44 , although CCK is widely used as an interneuron marker in cortical areas. Further investigations would be needed to decipher the role of one of the most abundant interneuron classes in the human striatum.…”

Section: Discussionmentioning

confidence: 99%

Interneuron diversity in the human dorsal striatum

Garma

Harder

Barba-Reyes

et al. 2023

Preprint

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Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangle the complex neurological and psychiatric diseases affecting this brain structure. We performed single-nucleus RNA-sequencing (snRNA-seq) of postmortem human caudate nucleus (CN) and putamen (Pu) samples to elucidate the diversity and abundance of interneuron populations and their transcriptional structure in the human dorsal striatum. We propose a new taxonomy of striatal interneurons with eight main classes. We provide specific markers for all subclasses and validated some of them with quantitative in situ fluorescence hybridization, such as a novel PTHLH-expressing population that exhibits different abundance and gene expression between CN and Pu. For the most abundant interneuron populations in human striatum, PTHLH and TAC3, we found matching known mouse interneuron populations based on key functional genes such as ion channels and synaptic receptors. Remarkably, human TAC3 and mouse Th populations share important similarities including the expression of the neuropeptide tachykinin 3. Finally, we were able to integrate our dataset with several prior smaller human striatal snRNA-seq studies, thus supporting the generalizability of this new harmonized taxonomy.

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Section: Discussionmentioning

confidence: 99%

Interneuron diversity in the human dorsal striatum

Garma

Harder

Barba-Reyes

et al. 2023

Preprint

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“…In fact, CCK appears to be involved in female’s reproductive behavior (Liu and Cao, 2022; Yin et al, 2022). A sex difference is also observed in CCK neuron activity and CCK receptor signaling in modulating drug intake and drug-seeking in rodent (Ma and Giardino, 2022). These data emphasize the need to examine sex and hormonal influences in CCK response and more generally in biology and health.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, CCK appears to be involved in female's reproductive behavior (Liu and Cao, 2022;Yin et al, 2022). A sex difference is also observed in CCK neuron activity and CCK receptor signaling in modulating drug intake and drug-seeking in rodent (Ma and Giardino, 2022).…”

Section: Cck2r Antagonist Impairs Male Motor Coordinationmentioning

confidence: 99%

Cholecystokinin exerts a major control on corticostriatal synapse and motor behavior

Guillaume¹,

Sáez

Castellano³

et al. 2022

Preprint

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Cholecystokinin (CCK) is a neuropeptide detected and produced at high concentrations in the brain. To date it was mainly used as a neuronal marker of neuronal subtypes and its role as a neuromodulator was poorly known. However, few studies showed that it could be an essential neuromodulator in various brain structures, playing a role on synaptic plasticity and memory consolidation. In order to better understand the processes by which CCK impacts plasticity, we focus our attention on the striatum, a nucleus involved in procedural learning and motor behavior, with a rich expression of CCK receptor type 2 (CCK2R). By using in-vivo and ex-vivo electrophysiological approaches, we show that CCK is involved in the corticostriatal synaptic transmission and has a key role in its plasticity. Using in-vivo optopatch-clamp of identified MSNs, we observe a decrease of corticostriatal synaptic transmission after an injection of CCK2R antagonist, leading to a reduction of evoked excitatory post synaptic potential rec-orded on both MSNs populations (direct and indirect pathways). In addition, we evaluate the impact of CCK2R antagonist on corticostriatal synaptic plasticity using Spike Timing Dependent Plasticity (STDP) protocols on MSNs of acute rat brain slices. Results demonstrate that the CCK2R antagonist is able to reverse the corticostriatal synaptic plasticity (i.e. LTP protocol leads to LTD). Finally, we evaluate the effect of CCK2R antagonist on the motor behavior of juvenile rats challenged with different locomotor tests and show a sex-dependent impairment of motor behavior. Overall, our results demonstrate that CCK and its receptor CCK2R are es-sential for inputs processing encoding in the corticostriatal network with consequences on motor activity.

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“…Remarkably, we nd an important increase of CCK-expressing cells in human vs. mouse dorsal striatum, which might indicate its greater involvement in highly complex computational processes for motor and cognitive functions in the human. Little is known about the role of CCKexpressing cells in the central nervous system 44 , although CCK is widely used as an interneuron marker in cortical areas. Further investigations would be needed to decipher the role of one of the most abundant interneuron classes in the human striatum.…”

Section: Interneuron Diversity In the Human Striatum Is Higher Than E...mentioning

confidence: 99%

Interneuron diversity in the human dorsal striatum

Garma

Harder

Barba-Reyes

et al. 2023

Preprint

View full text Add to dashboard Cite

Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangle the complex neurological and psychiatric diseases affecting this brain structure. We performed snRNA-seq of postmortem human caudate nucleus and putamen samples to elucidate the diversity and abundance of interneuron populations and their transcriptional structure in the human dorsal striatum. We propose a new taxonomy of striatal interneurons with eight main classes and fourteen subclasses and provide their specific markers and some quantitative FISH validation, particularly for a novel PTHLH-expressing population. For the most abundant populations, PTHLH and TAC3, we found matching known mouse interneuron populations based on key functional genes such as ion channels and synaptic receptors. Remarkably, human TAC3 and mouse Th populations share important similarities including the expression of the neuropeptide tachykinin 3. Finally, we were able to integrate other published datasets supporting the generalizability of this new harmonized taxonomy.

show abstract

Neural circuit mechanisms of the cholecystokinin (CCK) neuropeptide system in addiction

Cited by 15 publications

References 83 publications

Interneuron diversity in the human dorsal striatum

Interneuron diversity in the human dorsal striatum

Cholecystokinin exerts a major control on corticostriatal synapse and motor behavior

Interneuron diversity in the human dorsal striatum

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