Increase in cortical endocannabinoid signaling in a rat model of basal forebrain cholinergic dysfunction

Llorente-Ovejero, Alberto; Manuel, Iván; Rodrı́guez-Puertas, Rafael

doi:10.1016/j.neuroscience.2017.08.008

Cited by 18 publications

(29 citation statements)

References 64 publications

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“…We recently found that disrupting OFC function abolished control of discrimination accuracy by signaled reward probability in our task ( Ward et al, 2015b ; Hall-McMaster et al, 2017 ) similarly to what we found here. Finally, other signaling pathways in the BF-prefrontal circuit, such as the endocannabinoid system, have recently been identified as important in BF modulation of cortical activity and in the processing of reward-driven motivational salience ( Llorente-Ovejero et al, 2017 ; Brancato et al, 2018 ). Clearly, further work that delineates the specific neural populations and timecourse of neural activity involved in SPSA performance is needed in order to clarify the specific role of cholinergic and non-cholinergic BF projections neurons and other circuitry in the effects seen here.…”

Section: Discussionmentioning

confidence: 99%

Basal Forebrain Mediates Motivational Recruitment of Attention by Reward-Associated Cues

Tashakori-Sabzevar

Ward

2018

Front. Neurosci.

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The basal forebrain, composed of distributed nuclei, including substantia innominata (SI), nucleus basalis and nucleus of the diagonal band of Broca plays a crucial neuromodulatory role in the brain. In particular, its projections to the prefrontal cortex have been shown to be important in a wide variety of brain processes and functions, including attention, learning and memory, arousal, and decision-making. In the present study, we asked whether the basal forebrain is involved in recruitment of cognitive effort in response to reward-related cues. This interaction between motivation and cognition is critically impacted in psychiatric conditions such as schizophrenia. Using the Designer Receptor Exclusively Activated by Designer Drug (DREADD) technique combined with our recently developed signaled probability sustained attention task (SPSA), which explicitly assays the interaction between motivation and attention, we sought to determine the role of the basal forebrain in this interaction. Rats were stereotaxically injected in the basal forebrain with either hM4D(Gi) (a virus that expresses receptors which silence neurons in the presence of the drug clozapine-N-oxide; CNO) or a control virus and tested in the SPSA. Behavior of rats during baseline and under saline indicated control by reward probability. In the presence of CNO, differential accuracy of hM4D(Gi) rats on high and low reward-probability trials was abolished. This result occurred despite spared ability of the reward-probability signals to differentially impact choice-response latencies and omissions. These results indicate that the basal forebrain is critical for the motivational recruitment of attention in response to reward-related cues and are consistent with a role for basal forebrain in encoding and transmitting motivational salience of reward-related cues and readying prefrontal circuits for further attentional processing.

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Section: Discussionmentioning

confidence: 99%

Basal Forebrain Mediates Motivational Recruitment of Attention by Reward-Associated Cues

Tashakori-Sabzevar

Ward

2018

Front. Neurosci.

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“…After 20 s exploration, the door opened and the step‐through latency time to enter the black‐closed compartment was measured. In this test session, maximum cut‐off time was 150 s …”

Section: Methodsmentioning

confidence: 99%

Thymoquinone Can Improve Neuronal Survival and Promote Neurogenesis in Rat Hippocampal Neurons

Beker

Dalli

Elibol

2018

Molecular Nutrition Food Res

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“…Different groups have reported increases [19], decreases [20], or no changes [21] in CB 1 receptor levels in several brain areas (at the mRNA, protein, or receptor coupling efficiency) in the past few years. The current perception is that CB 1 receptors may play a role in the progression of AD, but it is difficult to establish the precise role(s) in which they might contribute.…”

Section: The Endocannabinoid System In Alzheimer's Diseasementioning

confidence: 99%

Cannabinoid pharmacology/therapeutics in chronic degenerative disorders affecting the central nervous system

Aymerich

Aso

Abellanas

et al. 2018

Biochemical Pharmacology

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The endocannabinoid system (ECS) exerts a modulatory effect of important functions such as neurotransmission, glial activation, oxidative stress, or protein homeostasis. Dysregulation of these cellular processes is a common neuropathological hallmark in aging and in neurodegenerative diseases of the central nervous system (CNS). The broad spectrum of actions of cannabinoids allows targeting different aspects of these multifactorial diseases. In this review, we examine the therapeutic potential of the ECS for the treatment of chronic neurodegenerative diseases of the CNS focusing on Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. First, we describe the localization of the molecular components of the ECS and how they are altered under neurodegenerative conditions, either contributing to or protecting cells from degeneration. Second, we address recent advances in the modulation of the ECS using experimental models through different strategies including the direct targeting of cannabinoid receptors with agonists or antagonists, increasing the endocannabinoid tone by the inhibition of endocannabinoid hydrolysis, and activation of cannabinoid receptor-independent effects. Preclinical evidence indicates that cannabinoid pharmacology is complex but supports the therapeutic potential of targeting the ECS. Third, we review the clinical evidence and discuss the future perspectives on how to bridge human and animal studies to develop cannabinoid-based therapies for each neurodegenerative disorder. Finally, we summarize the most relevant opportunities of cannabinoid pharmacology related to each disease and the multiple unexplored pathways in cannabinoid pharmacology that could be useful for the treatment of neurodegenerative diseases.

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Increase in cortical endocannabinoid signaling in a rat model of basal forebrain cholinergic dysfunction

Cited by 18 publications

References 64 publications

Basal Forebrain Mediates Motivational Recruitment of Attention by Reward-Associated Cues

Basal Forebrain Mediates Motivational Recruitment of Attention by Reward-Associated Cues

Thymoquinone Can Improve Neuronal Survival and Promote Neurogenesis in Rat Hippocampal Neurons

Cannabinoid pharmacology/therapeutics in chronic degenerative disorders affecting the central nervous system

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