Article
Neurosciences
Travis M. Moschak, T. Joseph Sloand, Regina M. Carelli
Summary: Distress tolerance (DT) is the ability to persist in challenging goal-directed behavior in the face of stress. Preclinical study in rats reveals that low DT is associated with heightened drug-seeking behavior. The study also demonstrates that the prelimbic cortex (PrL) plays an important role in DT and drug-seeking behavior, particularly in male rats with a history of cocaine.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Cell Biology
Lanfang Yu, Chenshan Chu, Yu Yuan, Xinli Guo, Chao Lei, Huan Sheng, Li Yang, Dongyang Cui, Bin Lai, Ping Zheng
Summary: The study highlights the important role of the paraventricular nucleus of the thalamus (PVT) in the retrieval of morphine withdrawal memory, and indicates that the activity of PrL-PVT projection neurons is necessary for this process. Moreover, the conditioned context induces plastic changes in the activity of these projection neurons during withdrawal memory retrieval.
Article
Pharmacology & Pharmacy
Anuja R. Bony, Jeffrey R. McArthur, Rocio K. Finol-Urdaneta, David J. Adams
Summary: This study is the first to report the potentiation of GIRK channels via allosteric alpha-conotoxin Vc1.1-GABA(B) receptor agonism, leading to decreased neuronal excitability. This finding contributes to the understanding of the analgesic effects of Vc1.1 and baclofen in vivo.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Anuja R. Bony, Jeffrey R. McArthur, Rocio K. Finol-Urdaneta, David J. Adams
Summary: The study shows that analgesic alpha-conotoxins potentiate GIRK channels via GABA(B) receptor-dependent mechanisms, leading to decreased neuronal excitability.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Xiaofeng Han, Shuxia Guo, Nan Ji, Tian Li, Jian Liu, Xiangqiao Ye, Yi Wang, Zhixi Yun, Feng Xiong, Jing Rong, Di Liu, Hui Ma, Yujin Wang, Yue Huang, Peng Zhang, Wenhao Wu, Liya Ding, Michael Hawrylycz, Ed Lein, Giorgio A. Ascoli, Wei Xie, Lijuan Liu, Liwei Zhang, Hanchuan Peng
Summary: In this study, a unique approach was proposed to collect three-dimensional images of brain neurons by injecting dyes into patients' brain tissues. The research found that human neurons are more diverse across brain regions than by subject age or gender. Furthermore, the strong stereotypy within brain region cohorts allows for the generation of a statistical tensor field of neuron morphology to characterize the anatomical modularity of a human brain.
Article
Multidisciplinary Sciences
Cong Wang, Peter G. Stratton, Pankaj Sah, Roger Marek
Summary: Fear learning and its extinction are important processes for responding to aversive events and threats. This study investigated the neural mechanisms underlying fear learning and its relapse. The findings suggest that synchronized activity between the different subregions of the medial prefrontal cortex is crucial for the context-dependent retrieval of fear extinction memory.
Article
Clinical Neurology
Julian Guarque-Chabrera, Isis Gil-Miravet, Francisco Olucha-Bordonau, Ignasi Melchor-Eixea, Marta Miquel
Summary: Reciprocal pathways between the cerebellum and prefrontal cortex play a crucial role in modulating cognitive functions and psychiatric disorders related to substance use. Cue-action-reward associations in individuals with substance use disorder can trigger craving and relapse, with cerebellar activations observed during drug-related cue presentations. Inactivation of the Infralimbic cortex in rats during cocaine-induced conditioning led to increased preference for drug-related cues, enhanced cerebellar activity, and altered expression of perineuronal nets around Golgi interneurons, suggesting a potential role of cerebellar dysfunction in facilitating drug-induced memory acquisition.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Article
Neurosciences
Reginald Cannady, Tiffany Nguyen, Audrey E. Padula, Jennifer A. Rinker, Marcelo F. Lopez, Howard C. Becker, John J. Woodward, Patrick J. Mulholland
Summary: The interaction between ethanol and stress may lead to increased alcohol consumption, cognitive deficits, and negative affective behaviors in mice. Ethanol exposure results in structural adaptations, while repeated stress exposure drives functional changes in prefrontal and infralimbic cortical neurons, suggesting distinct morphological and functional alterations may underlie excessive drinking and cognitive deficits associated with ethanol-stress interactions.
Article
Cell Biology
Rym Aouci, Mey El Soudany, Zakaria Maakoul, Anastasia Fontaine, Hiroki Kurihara, Giovanni Levi, Nicolas Narboux-Neme
Summary: The study found that the regulation of Dlx5/6 genes in adult GABAergic neurons has a direct impact on the density of PV-positive neurons, anxiety and compulsivity-like behaviors, reinforcing their importance in neuropsychiatric conditions.
Article
Biochemistry & Molecular Biology
Elena Lopez-Terrones, Veronica Paz, Leticia Campa, Sara Conde-Berriozabal, Merce Masana, Francesc Artigas, Maurizio S. Riga
Summary: The reciprocal connectivity between the medial prefrontal cortex (mPFC) and the dorsal raphe nucleus (DR) plays a role in mood control and stress resilience. The infralimbic subdivision (IL) of the mPFC, similar to the ventral anterior cingulate cortex, is associated with major depressive disorder (MDD). Stimulation of IL suppresses serotonergic activity more than stimulation of PrL, indicating the differential control of serotonergic activity by these two subdivisions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Yara Otor, Shay Achvat, Nathan Cermak, Hadas Benisty, Maisan Abboud, Omri Barak, Yitzhak Schiller, Alon Poleg-Polsky, Jackie Schiller
Summary: This study reveals the different tuft computational properties of layer 5 pyramidal tract neurons during motor tasks, indicating the potential morphologically dependent framework for motor computations.
Article
Multidisciplinary Sciences
Mohit Srivastava, Cintia Angel, Reka Eszter Kisvarday, Zsolt Kocsis, Andras Stelescu, Petra Talapka, Zoltan Kisvarday
Summary: This study reports the characteristics of a novel deep-layer neuron, which has distinct morphological and functional features. It has a large cell body and multiple spine-free dendrites, and its axon can project up to 2.8 mm before entering the white matter. The dendritic length, surface area, and volume of this neuron are significantly larger than other known cortical neuron types. The boutons of this neuron mainly target dendritic spines and show immunopositivity to GABA. Optical imaging reveals an uneven distribution of the boutons in different orientations. The layer 6 stellate neuron plays an important integrating role in deep cortical layers and other cortical and/or subcortical regions.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Victor Hugo Cornejo, Netanel Ofer, Rafael Yuste
Summary: Dendritic spines play a critical role in excitatory neurotransmission in the nervous system. The membrane potentials of spines and dendrites were measured during spontaneous activity and sensory stimulation in mice. Spines and dendrites were depolarized together during action potentials, but experienced different voltages during subthreshold and resting potentials. The regulation of voltage compartmentalization could have important implications for synaptic function and plasticity, dendritic integration, and disease states.
Article
Neurosciences
Veronica Lopez-Virgen, Rafael Olivares-Moreno, Victor de Lafuente, Luis Concha, Gerardo Rojas-Piloni
Summary: This study investigated the PTNs projecting to the red and pontine nuclei in the mouse motor cortex, revealing distinct subtypes that may contribute differently to sensorimotor integration.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Lou Beaulieu-Laroche, Norma J. Brown, Marissa Hansen, Enrique H. S. Toloza, Jitendra Sharma, Ziv M. Williams, Matthew P. Frosch, Garth Rees Cosgrove, Sydney S. Cash, Mark T. Harnett
Summary: The size of neurons influences their input-output features, with different species showing conservative rules of adaptation and human neurons exhibiting atypical behavior in terms of potassium and HCN conductance.
Article
Neurosciences
Timothy R. Rose, Ezequiel Marron Fernandez de Velasco, Baovi N. Vo, Megan E. Tipps, Kevin Wickman
Summary: Drug-induced neuroadaptations in the mouse mPFC, specifically affecting pyramidal neurons in the prelimbic region, have been shown to increase cocaine-induced activity and disrupt trace fear learning. Enhancing the excitability of these neurons selectively replicates behavioral hallmarks of repeated cocaine exposure in mice.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Margot C. DeBaker, Ezequiel Marron Fernandez de Velasco, Nora M. McCall, Anna M. Lee, Kevin Wickman
Summary: Drugs of abuse enhance dopamine signaling in the mesocorticolimbic circuitry by engaging inhibitory G-protein-dependent feedback pathways in VTA DA neurons, influencing addiction-related behaviors.
Article
Pharmacology & Pharmacy
Allison Anderson, Baovi N. Vo, Ezequiel Marron Fernandez de Velasco, Corey R. Hopkins, C. David Weaver, Kevin Wickman
Summary: The newly identified GIRK channel inhibitor VU0468554 shows effective inhibition of cardiac GIRK channels, indicating promising therapeutic implications for relevant cardiac arrhythmias. Studies suggest that VU0468554 selectively targets cardiac over neuronal GIRK channels and partially reverses GIRK-mediated bradycardia in isolated mouse heart models.
MOLECULAR PHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Earnest L. Taylor, Samantha R. Weaver, Ian M. Lorang, Katherine M. Arnold, Elizabeth W. Bradley, Ezequiel Marron Fernandez de Velasco, Kevin Wickman, Jennifer J. Westendorf
Summary: Long bones are formed and repaired through the process of endochondral ossification. In this study, the role of GIRK channels in non-excitable cells involved in endochondral bone formation was investigated. The results showed that Girk3 controls several processes involved in bone lengthening, including collagen and VEGF receptor-related gene expression, micromass production, and response to kappa opioid receptor ligand. This suggests that GIRK3 plays a crucial role in skeletal development and long bone growth.
Article
Multidisciplinary Sciences
Alexander G. J. Skorput, Reshma Gore, Rachel Schorn, Maureen S. Riedl, Ezequiel Marron Fernandez de Velasco, Bailey Hadlich, Kelley F. Kitto, Carolyn A. Fairbanks, Lucy Vulchanova
Summary: This study compared the transduction patterns of neurons using AAV9 and AAV2retro vectors. The results revealed notable differences in the access of the two AAV serotypes to primary afferent neurons in the colon and spinal projection neurons in the parabrachial complex. Additionally, the study emphasized the superior sensitivity of neuronal transduction detection based on reporter gene expression compared to viral protein expression.
Review
Biochemistry & Molecular Biology
Ana Fajardo-Serrano, Alberto J. Rico, Elvira Roda, Adriana Honrubia, Sandra Arrieta, Goiaz Ariznabarreta, Julia Chocarro, Elena Lorenzo-Ramos, Alvaro Pejenaute, Alfonso Vazquez, Jose Luis Lanciego
Summary: The gene therapy field, particularly targeting neurodegenerative disorders, is currently in the spotlight due to the development of new therapeutics. With the increasing number of ongoing clinical trials, providing advice on the best delivery route for AAV-based therapeutic approaches is crucial for beginners.
Review
Cell Biology
Haichang Luo, Ezequiel Marron Fernandez de Velasco, Kevin Wickman
Summary: G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels play a critical inhibitory role in neurons. They are regulated by G proteins, phosphatidylinositol 4,5-bisphosphate (PIP2), phosphorylation, regulator of G protein signaling (RGS) proteins, as well as intracellular Na+ and Ca2+. Various stimuli can modify neuronal GIRK channel activity transiently or persistently, including exposure to drugs of abuse, changes in neuronal activity patterns, and aversive experience. Dysregulation of GIRK channel activity has been implicated in neurological diseases and disorders.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Clinical Neurology
Rocio Alfaro-Ruiz, Carolina Aguado, Alejandro Martin-Belmonte, Ana Esther Moreno-Martinez, Jesus Merchan-Rubira, Felix Hernandez, Jesus Avila, Yugo Fukazawa, Rafael Lujan
Summary: N-methyl-D-aspartate receptors are important in Alzheimer's disease, and their expression and localization differ at synaptic and extrasynaptic sites, which is associated with accumulation of phospho-tau.
Article
Biochemistry & Molecular Biology
Kira D. A. Rienecker, Robert G. Poston, Joshua S. Segales, Isabelle W. Finholm, Morgan H. Sono, Sorina J. Munteanu, Mina Ghaninejad-Esfahani, Ayna Rejepova, Susana Tejeda-Garibay, Kevin Wickman, Ezequiel Marron Fernandez de Velasco, Stanley A. Thayer, Ramendra N. Saha
Summary: This study found that mild depolarization induces a wide array of IEGs and transiently depresses transcriptional and signaling responses to a successive stimulus. Furthermore, mild depolarization acutely subdues subsequent spontaneous and bicuculline-evoked activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Timothy R. Rose, Ezequiel Marron Fernandez de Velasco, Eric H. Mitten, Kevin Wickman
Summary: Drug-induced neuroadaptations in the prefrontal cortex (PFC) have been linked to drug-associated memories. This study found that ablation of GIRK channels and GABA(B) receptors did not affect acquisition of cocaine-related memories, but GIRK channel ablation impaired extinction of cocaine-related memories in male mice. Increasing GIRK channel activity accelerated the extinction of cocaine-related memories.
Article
Biochemistry & Molecular Biology
Rocio Alfaro-Ruiz, Carolina Aguado, Alejandro Martin-Belmonte, Ana Esther Moreno-Martinez, Jesus Merchan-Rubira, Felix Hernandez, Jesus Avila, Yugo Fukazawa, Rafael Lujan
Summary: The accumulation of tau proteins in diseases like Alzheimer's disease is associated with alterations in glutamate receptor dynamics, leading to synaptic dysfunction. This study investigated the impact of tau pathology on AMPAR expression, density, and distribution in the hippocampus of P301S mice. The results showed that the accumulation of phospho-tau resulted in reduced AMPAR density in excitatory synapses on pyramidal cell spines and interneuron dendrites, as well as at extrasynaptic sites in CA1 pyramidal cells and interneurons. These findings suggest that tau pathology disrupts AMPAR trafficking and synaptic transmission, contributing to the pathological events in Alzheimer's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Margot C. DeBaker, Eric H. Mitten, Timothy R. Rose, Ezequiel Marron Fernandez de Velasco, Runbo Gao, Anna M. Lee, Kevin Wickman
Summary: This study found that RGS6 protein negatively regulates inhibitory G protein signaling pathways in VTA dopamine neurons in mice and has a sex-dependent positive influence on binge-like alcohol consumption in adult mice.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemical Research Methods
Kevin Lin, Ya-Chu Chang, Ezequiel Marron Fernandez de Velasco, Kevin Wickman, Chad L. Myers, Anja-Katrin Bielinsky
Summary: This scalable approach for high-throughput compound screening utilizing a small custom library provides higher coverage and greater timepoint resolution compared to genome-wide screens.