Article
Pharmacology & Pharmacy
Kevin Clare, Chelsea Pan, Gloria Kim, Kicheon Park, Juan Zhao, Nora D. Volkow, Zhicheng Lin, Congwu Du
Summary: The study revealed increased density of D2r-positive cells in the medial prefrontal cortex and ventral tegmental area of both male and female mice passively exposed to chronic cocaine, alongside an overall decrease in neuronal density. Higher levels of Drd2 mRNA in the mPFC and Dstr of female mice exposed to cocaine suggest limited sensitivity of the method used. This shift in neuronal phenotype and potential cognitive impairments warrant further investigation.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mathilde C. C. Guillaumin, Paulius Viskaitis, Eva Bracey, Denis Burdakov, Daria Peleg-Raibstein
Summary: Overeating is driven by both the hedonic component ('liking') of food and the motivation ('wanting') to eat it. The nucleus accumbens (NAc) plays a key role in encoding 'liking' and 'wanting', but the specific contributions of different NAc cell populations are unclear. This study used cell-specific recording and optogenetic manipulation in mice to investigate the roles of NAc D1 and D2 cells in 'liking' and 'wanting'. The findings revealed complementary roles of D1 and D2 cells in consumption, assigning neural bases to 'liking' and 'wanting' in a unifying framework of D1 and D2 cell activity.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Zheng-Dong Zhao, Xiao Han, Renchao Chen, Yiqiong Liu, Aritra Bhattacherjee, Wenqiang Chen, Yi Zhang
Summary: The striatum plays a critical role in regulating addiction-related behaviors. A subtype of D1 MSNs, Tac2+, demonstrates an unconventional and subtype/projection-specific negative regulatory function in drug addiction.
Article
Neurosciences
Jenya Kolpakova, Vincent van der Vinne, Pablo Gimenez-Gomez, Timmy Le, Gilles E. Martin
Summary: Animal studies support the important role of striatal cholinergic interneurons in basal ganglia function, particularly in associative learning, reward processing, and motor control. ChIs regulate synaptic excitability of medium spiny neurons by modulating dopamine, glutamate, and GABA neurotransmission. The effect of ChIs on dopamine D1- and D2 receptor-expressing neurons differs, and is altered after binge alcohol drinking.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Behavioral Sciences
Jiaxin Tang, Chengmei Yang, Mengwen Shi, Weihai Chen
Summary: Conditioned avoidance responses (CAR) behavior is a widely used paradigm for studying aversive conditioning and defensive motivation behavior. This study found that activation of dopamine D-2 receptors in the shell of nucleus accumbens evokes CAR behavior, while activation of dopamine D-1 receptors and dorsolateral striatum does not. This suggests that the shell of nucleus accumbens is the critical brain region for dopamine to elicit CAR behavior, and activation of dopamine D-2 receptors in the shell of nucleus accumbens is sufficient and necessary for triggering CAR behavior.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Article
Neurosciences
Xiao-Bo Wu, Qian Zhu, Ming-Hui Gao, Sheng-Xiang Yan, Pan-Yang Gu, Peng-Fei Zhang, Meng-Lin Xu, Yong-Jing Gao
Summary: Itch is a complex sensation regulated by neural circuits involving the nucleus accumbens (NAc) and excitatory afferents from the medial prefrontal cortex (mPFC), amygdala, and hippocampus. This study reveals that acute itch decreases the intrinsic membrane excitability in dopamine receptor D1-expressing medium spiny neurons (Drd1-MSNs) in the NAc core, and that chemogenetic activation of Drd1-MSNs alleviates itch-induced scratching behaviors. Furthermore, it was found that excitatory synaptic afferents from the mPFC play a crucial role in itch modulation.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Tong-Yu Liang, Hua Zhou, Yan-Gang Sun
Summary: Ventral tegmental area (VTA) dopaminergic neurons participate in itch processing through their projection to the nucleus accumbens (NAc). The roles of dopamine receptor subtypes in different subregions of the NAc during itch processing were investigated. It was found that dopamine D1 receptors (D1R) blockade in the lateral shell (LaSh) impaired pruritogen-induced scratching behavior, while D2R activation in both LaSh and medial shell (MeSh) attenuated scratching behavior. Dopamine release in LaSh was elevated during scratching behavior, suggesting a motivational component of itch processing. This study highlights the importance of D1R in the LaSh of the NAc in itch signal processing.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
J. Daniel Obray, Christina A. Small, Emily K. Baldwin, Eun Young Jang, Jin Gyeom Lee, Chae Ha Yang, Jordan T. Yorgason, Scott C. Steffensen
Summary: This study found that peripherally administered dopamine can enhance dopamine levels in the nucleus accumbens and modulate related behaviors. Dopamine subtype-2 receptors are involved in this process and can influence dopamine neuron activity.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Behavioral Sciences
Yi Zhang, Huan Gui, Lang Hu, Chengxi Li, Jie Zhang, Xiaoli Liang
Summary: Aging delays emergence from anesthesia in elderly mice, with changes in EEG power. The activation or inhibition of D1R in the NAc shell modulates emergence in young mice, but this capacity declines in aged mice along with decreased D1R expression in the NAc shell.
BRAIN AND BEHAVIOR
(2021)
Article
Biochemistry & Molecular Biology
Yi Zhang, Huan Gui, Zikun Duan, Tian Yu, Jie Zhang, Xiaoli Liang, Chengxi Liu
Summary: Systemic activation of D1 receptors has been found to promote emergence from propofol-induced unconsciousness, with the nucleus accumbens (NAc) showing disinhibited neuronal activity during the recovery phase. D1 receptor modulation on the activity of NAc MSNs plays a vital role in facilitating the emergence from propofol-induced unconsciousness, as shown by whole-cell patch clamp recordings and pharmacological intervention experiments.
NEUROCHEMICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Anna Kruyer, Jeffrey Parrilla-Carrero, Courtney Powell, Lasse Brandt, Stefan Gutwinski, Ariana Angelis, Reda M. Chalhoub, Thomas C. Jhou, Peter W. Kalivas, Davide Amato
Summary: Antipsychotic-induced dopamine supersensitivity is a problematic consequence of long-term antipsychotic treatment, characterized by motor abnormalities, refractory symptoms, and rebound psychosis. This phenomenon is associated with long-lasting synaptic plasticity and hyperexcitability in a subpopulation of D2 receptor-expressing neurons, leading to behavioral endophenotypes of treatment resistance and substance use disorder. Chemogenetic restoration of inhibitory postsynaptic currents may offer a novel therapeutic direction for preventing antipsychotic-induced supersensitivity.
MOLECULAR PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Daniel J. Christoffel, Jessica J. Walsh, Paul Hoerbelt, Boris D. Heifets, Pierre Llorach, Ricardo C. Lopez, Charu Ramakrishnan, Karl Deisseroth, Robert C. Malenka
Summary: The study reveals that dopamine and serotonin modulate excitatory synaptic transmission in the nucleus accumbens in input-specific ways, influencing motivated behaviors differently. Endogenous release of DA and 5-HT, as well as optogenetic inhibition, alter the behavioral effects of drugs in distinct manners.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Dan P. Covey, Edith Hernandez, Miguel A. Lujan, Joseph F. Cheer
Summary: The study found that dopamine release in the nucleus accumbens responds differently to cues signaling increasing cost of reward. Endocannabinoid signaling facilitates goal-seeking and nucleus accumbens dopamine release, while chronic MAGL treatment stably facilitates goal-seeking and dopamine encoding without the development of tolerance.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Pharmacology & Pharmacy
Richard B. Mailman, Yang Yang, Xuemei Huang
Summary: Research suggests that selective D-1 agonists may play a critical role in the treatment of Parkinson's disease, providing profound symptomatic relief even when current drugs are ineffective. Existing Parkinson's medications have limited efficacy in severe cases, but high intrinsic activity D-1 agonists could offer a major therapeutic advance in improving patients' quality of life.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Qiuping Tong, Xiao Cui, Hao Xu, Xiaoshuang Zhang, Songhui Hu, Fang Huang, Lei Xiao
Summary: Dopamine plays a key role in regulating emotion, and the dysfunction of dopamine signal has been linked to psychiatric disorders such as anxiety. The Ventral tegmental area (VTA) is an important region with dopamine-producing neurons. This study demonstrates that activation/inhibition of D1 receptors in the VTA can alleviate/aggravate anxiety-like behaviors in mice, and knocking down D1 receptor expression in the VTA also has an anxiogenic effect. The functional expression of D1 receptors in VTA neurons was confirmed using fluorescence in situ hybridization and electrophysiological recording.
MOLECULAR PSYCHIATRY
(2023)
Article
Clinical Neurology
Rachel-Karson Theriault, Joshua D. Manduca, Colin R. Blight, Jibran Y. Khokhar, Tariq A. Akhtar, Melissa L. Perreault
JOURNAL OF PSYCHOPHARMACOLOGY
(2020)
Article
Cell Biology
Abdalla M. Albeely, Olivia O. F. Williams, Melissa L. Perreault
Summary: The study suggests that increased activity of GSK-3 beta (S9A) in the PFC or vHIP of rats affects neuronal oscillatory activity and leads to deficits in learning and memory. These changes are accompanied by aberrant phosphorylation of tau protein. Therefore, abnormal GSK-3 beta signaling may contribute to cognitive dysfunction disorders.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rachel-Karson Theriault, Myles St-Denis, Tristen Hewitt, Jibran Y. Khokhar, Jasmin Lalonde, Melissa L. Perreault
Summary: The study reveals that CBD induces rapid increases in cortical neuronal activity and sex-specific drug interactions upon coadministration with ILO, indicating the need to consider sex when implementing adjunct therapy for the treatment of SZ.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Shoshana Buckhalter, Eric Soubeyrand, Sarah A. E. Ferrone, Duncan J. Rasmussen, Joshua D. Manduca, M. Sameer Al-Abdul-Wahid, Jude A. Frie, Jibran Y. Khokhar, Tariq A. Akhtar, Melissa L. Perreault
Summary: Krakom, a traditional herbal medicine used to enhance mood and alleviate pain, has shown increased usage in Europe and North America. The study evaluated the effects of purified alkaloid kratom extract on neuronal oscillatory systems, pain relief, and antidepressant-like behavior, as well as kratom-induced changes in Delta FosB expression. The results suggest that kratom has both antidepressant and analgesic properties, with specific changes in neuronal circuit function, but does not affect the Delta FosB signaling pathway known to be involved in addiction.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Cell Biology
Ryan T. McCallum, Melissa L. Perreault
Summary: This study discussed the widespread multi-system involvement of GSK-3 in contributing to the neuropathology of MDD, emphasizing the feed-forward mechanistic links between all major neuronal signaling pathways.
Review
Neurosciences
Olivia O. F. Williams, Madeleine Coppolino, Susan R. George, Melissa L. Perreault
Summary: Dopamine is a key neurotransmitter in neuropsychiatric illness, and sex differences play an important role in dopamine signaling. Understanding sex differences is crucial for personalized therapeutic strategies.
Editorial Material
Clinical Neurology
Melissa L. Perreault, Malcolm King, Chelsea Gabel, Christopher J. Mushquash, Yves De Koninck, Ashley Lawson, Caterina Marra, Caroline Menard, Jennie Z. Young, Judy Illes
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2023)
Review
Psychiatry
Olivia O. F. Williams, Madeleine Coppolino, Melissa L. Perreault
Summary: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with significant sex differences in memory, cognitive flexibility, verbal fluency, and social communication. Despite the lack of information on sex-dependent mechanisms of ASD and sex-specific symptoms, individuals across the spectrum often receive standardized diagnoses.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Thomas Parmentier, Fiona M. K. James, Elizabeth Hewitson, Craig Bailey, Nicholas Werry, Steven D. Sheridan, Roy H. Perlis, Melissa L. Perreault, Luis Gaitero, Jasmin Lalonde, Jonathan LaMarre
Summary: Activity-induced neurogenesis has been widely studied in rodents but less in humans. In this study, neuronal activity and associated neurogenesis were investigated in cerebral spheroids derived from human induced pluripotent stem cells (iPSCs). The results show that 4AP increases neuronal activity, promotes the generation of new neurons, and reduces the number of new glial cells. Furthermore, the expression of miR-135a, a key regulator of exercise-induced neurogenesis, was significantly decreased, suggesting its involvement in the process. These findings highlight the potential of iPSC-derived cerebral spheroids as a model for studying activity-induced neurogenesis.
SCIENTIFIC REPORTS
(2022)
Review
Neurosciences
Caitlin J. Nolan, Troy A. Roepke, Melissa L. Perreault
Summary: Schizophrenia research has largely ignored transgender and gender-nonconforming populations, resulting in limited understanding of their risk for the disorder. This review emphasizes the need for inclusion and discusses potential factors contributing to the elevated risk. Strategies for making research more inclusive are also offered.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Neurosciences
Abdalla M. Albeely, Caitlin J. Nolan, Duncan J. Rasmussen, Craig D. C. Bailey, Melissa L. Perreault
Summary: This study evaluated the impact of prefrontal cortical dopamine D5 receptor (D5R) knockdown on learning and memory in rats, and also assessed the role of D5R in the regulation of neuronal oscillatory activity and glycogen synthase kinase-3 beta (GSK-3 beta). The results showed that knockdown of D5R led to deficits in learning and memory, accompanied by increased theta oscillations in the prefrontal cortex, orbitofrontal cortex, and hippocampus, increased coherence between prefrontal cortex and orbitofrontal cortex, and decreased coherence between prefrontal cortex and thalamus.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Tristen Hewitt, Beguem Alural, Manali Tilak, Jennifer Wang, Natalina Becke, Ellis Chartley, Melissa Perreault, Stephen J. Haggarty, Steven D. Sheridan, Roy H. Perlis, Nina Jones, Nikolaos Mellios, Jasmin Lalonde
Summary: Research has found abnormal calcium signaling and neural development in bipolar disorder (BD) patient induced pluripotent stem cell-derived neural progenitor cells (BD-NPCs) and neurons. BD-NPCs showed attenuated store-operated calcium entry (SOCE) and accelerated neurodifferentiation. They also exhibited slower proliferation, increased neurite outgrowth, and decreased neurosphere formation, as well as decreased subventricular areas in developing BD cerebral organoids. BD-NPCs had high expression of the let-7 family and BD neurons had increased miR-34a, both of which are microRNAs implicated in neurodevelopment and BD etiology.
MOLECULAR PSYCHIATRY
(2023)
Review
Pharmacology & Pharmacy
Miles Schaffrick, Melissa L. Perreault, A. Maxwell P. Jones, Judy Illes
Summary: This study conducted a rapid scoping review to analyze 68 empirical studies on cannabis use among Indigenous peoples. The majority of studies focused on substance use disorders, prevalence rates, predictors, and motivators for use. The research identified a lack of empirical studies exploring the lived experiences of Indigenous peoples and cannabis, as well as a lack of transparency regarding author positionality.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Meeting Abstract
Neurosciences
Rachel-Karson Theriault, Joshua Manduca, Melissa Perreault
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Rachel-Karson Theriault, Joshua D. Manduca, Melissa L. Perreault
Summary: The study found that female rats exhibited higher theta coherence in hippocampal connections at baseline, and both female and male rats had different neural oscillatory patterns under stress exposure. Stress-susceptible animals showed distinct oscillatory changes, and stress exposure led to alterations in neural pathways that coincided with the onset of depression-like behaviors in a time-dependent manner.
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
(2021)
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.
