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Chronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivity.

ABSTRACT: Elucidating how cannabinoids affect brain function is instrumental for the development of therapeutic tools aiming to mitigate 'on target' side effects of cannabinoid-based therapies. A single treatment with the cannabinoid receptor agonist, WIN 55,212-2, disrupts recognition memory in mice. Here, we evaluate how prolonged, intermittent (30 days) exposure to WIN 55,212-2 (1 mg/kg) alters recognition memory and impacts on brain metabolism and functional connectivity. We show that chronic, intermittent treatment with WIN 55,212-2 disrupts recognition memory (Novel Object Recognition Test) without affecting locomotion and anxiety-like behaviour (Open Field and Elevated Plus Maze). Through 14 C-2-deoxyglucose functional brain imaging we show that chronic, intermittent WIN 55,212-2 exposure induces hypometabolism in the hippocampal dorsal subiculum and in the mediodorsal nucleus of the thalamus, two brain regions directly involved in recognition memory. In addition, WIN 55,212-2 exposure induces hypometabolism in the habenula with a contrasting hypermetabolism in the globus pallidus. Through the application of the Partial Least Squares Regression (PLSR) algorithm to the brain imaging data, we observed that prolonged WIN 55,212-2 administration alters functional connectivity in brain networks that underlie recognition memory, including that between the hippocampus and prefrontal cortex, the thalamus and prefrontal cortex, and between the hippocampus and the perirhinal cortex. In addition, our results support disturbed lateral habenula and serotonin system functional connectivity following WIN 55,212-2 exposure. Overall, this study provides new insight into the functional mechanisms underlying the impact of chronic cannabinoid exposure on memory and highlights the serotonin system as a particularly vulnerable target.

SUBMITTER: Mouro FM

PROVIDER: S-EPMC6220860 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Chronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivity.

Mouro Francisco M FM Ribeiro Joaquim A JA Sebastião Ana M AM Dawson Neil N

Journal of neurochemistry 20180927 1

Elucidating how cannabinoids affect brain function is instrumental for the development of therapeutic tools aiming to mitigate 'on target' side effects of cannabinoid-based therapies. A single treatment with the cannabinoid receptor agonist, WIN 55,212-2, disrupts recognition memory in mice. Here, we evaluate how prolonged, intermittent (30 days) exposure to WIN 55,212-2 (1 mg/kg) alters recognition memory and impacts on brain metabolism and functional connectivity. We show that chronic, intermi ...[more]

PMID: 29989183

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Project description:Brain connectivity analysis plays an essential role in the research of working memory that involves complex coordination of various brain regions. In this research, we present a comprehensive view of trans-states brain connectivity variation based on continuous scalp EEG, extending beyond traditional stimuli-lock averaging or restriction to short time scales of hundreds of milliseconds after stimulus onset. The scalp EEG was collected under three conditions: quiet, memory, and control. The only difference between the memory and control conditions was that in the memory condition, subjects made an effort to retain information. We started our investigation with calibrations of Pearson correlation in EEG analysis and then derived two indices, link strength and node connectivity, to make comparisons between different states. Finally, we constructed and studied trans-state brain connectivity variation topography. Comparing memory and control states with quiet state, we found that the beta topography highlights links between T5/T6 and O1/O2, which represents the visual ventral stream, and the gamma topography conveys strengthening of inter-hemisphere links and weakening of intra-hemisphere frontal-posterior links, implying parallel inter-hemisphere coordination combined with sequential intra-hemisphere coordination when subjects are confronted with visual stimuli and a motor task. For comparison between memory and control states, we also found that the node connectivity of T6 stands out in gamma topography, which provides strong proof from scalp EEG for the information binding or relational processing function of the temporal lobe in memory formation. To our knowledge, this is the first time for any method to effectively capture brain connectivity variation associated with working memory from a relatively large scale both in time (from a second to a minute) and in space (from the scalp). The method can track brain activity continuously with minimal manual interruptions; therefore, it has promising potential in applications such as brain computer interfaces and brain training.

Dataset Information

Chronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivity.

Publications

Chronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivity.

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