Article
Multidisciplinary Sciences
Shane B. Johnson, Ryan T. Lingg, Timothy D. Skog, Dalton C. Hinz, Sara A. Romig-Martin, Victor Viau, Nandakumar S. Narayanan, Jason J. Radley
Summary: This study explores the link between behavioral and biological features of stress responses in the brain. It identifies the involvement of the medial prefrontal cortex (mPFC) and midbrain dorsolateral periaqueductal gray (PAG) in active stress coping behaviors, while a different circuit involving the rostral mPFC and ventrolateral PAG limits passive behaviors. Furthermore, the activation of the caudal mPFC-dorsolateral PAG projection can attenuate the increase in stress hormone output and immobility associated with a passive coping response. These findings provide insights into how the brain coordinates different responses to stress and contributes to stress resilience.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Fernando M. C. V. Reis, Dean Mobbs, Newton S. Canteras, Avishek Adhikari
Summary: This article discusses the central role of the midbrain periaqueductal gray (PAG) in controlling various defensive responses and explores how PAG-centered circuits influence both innate and learned defensive actions in rodents and humans. It highlights the use of traditional methods like lesions, electrical stimulation, and pharmacology, as well as recent advancements in neural activity imaging and anatomical and genetic control methods to gain a better understanding of PAG function.
Article
Neurosciences
Lan Yang, Jingshan Lu, Jianpeng Guo, Jian Chen, Fangfang Xiong, Xinyao Wang, Li Chen, Changxi Yu
Summary: This study investigated the role of vlPAG astrocytes in diabetic neuropathic pain (DNP) using a multidimensional approach. The results showed that vlPAG astrocytes can regulate pain sensation and pain-related behaviors, and also alleviate anxiety-like behavior induced by DNP.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Acoustics
Yibo Wang, Lili Niu, Wen Meng, Zhengrong Lin, Junjie Zou, Tianyuan Bian, Xiaowei Huang, Hui Zhou, Long Meng, Ping Xie, Hairong Zheng
Summary: This study demonstrated that LIFUS stimulation of the PAG induced defensive behaviors in mice, without causing any injury to the brain tissue. LIFUS may be a novel neuromodulatory tool for treating psychological diseases associated with defensive behaviors.
IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL
(2021)
Article
Behavioral Sciences
Long Wang, Lu-Lan Fu, Zi-Ru Deng, Juan Zhang, Mei-Dan Zu, Jun-Cang Wu, Yu Wang
Summary: The overexpression of BDNF in vlPAG may have a protective effect, reducing pain sensitivity, scratching behavior, and spontaneous seizures in a comorbid model of epilepsy and migraine. This is accompanied by a decrease in c-Fos labeling neurons and CGRP immunoreactivity in TNC and TG.
BRAIN AND BEHAVIOR
(2022)
Article
Neurosciences
Yu Rao, Ziyan Gao, Xianping Li, Xing Li, Jun Li, Shanshan Liang, Daihan Li, Jinliang Zhai, Junan Yan, Jiwei Yao, Xiaowei Chen
Summary: The ventrolateral periaqueductal gray (VLPAG) plays a crucial role in controlling bladder function and has the potential to be a therapeutic target for neurogenic bladder dysfunction.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Ricardo P. Bindi, Cibele C. Guimaraes, Amanda R. de Oliveira, Fernando F. Melleu, Miguel A. X. de Lima, Marcus V. C. Baldo, Simone C. Motta, Newton S. Canteras
Summary: The present study systematically analyzed the afferent and efferent projections of the CUN and investigated its role in fear responses. The CUN was found to be a caudal component of the periaqueductal gray and had strong links with the dorsolateral periaqueductal gray. It was also found to mediate innate antipredatory responses but not learned fear responses.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Review
Cell Biology
Priscila Vazquez-Leon, Abraham Miranda-Paez, Kenji Valencia-Flores, Hugo Sanchez-Castillo
Summary: Serotonin is a crucial neurotransmitter that regulates various physiological processes and psychiatric disorders. The periaqueductal gray matter is an important center for defensive behaviors, and electrical stimulation in this region can induce panic, fight-flight, and freezing responses. Serotonergic activity in the periaqueductal gray matter is influenced by other brain areas and the activation of specific receptors, promoting serotonin release. This review emphasizes the role of 5-HT1A and 5-HT2A/C receptors in anxiety, panic, fear, analgesia, and aggression, suggesting their potential for the treatment of mental disorders.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Jeremy Signoret-Genest, Nina Schukraft, Sara L. Reis, Dennis Segebarth, Karl Deisseroth, Philip Tovote
Summary: In this study, the researchers identify rapid microstates that are associated with specific behaviors and heart rate dynamics. These microstates are affected by long-lasting macrostates and reflect context-dependent threat levels. The study also demonstrates that freezing behavior, as a defensive response, is part of an integrated cardio-behavioral microstate mediated by Chx10(+) neurons in the periaqueductal gray. The framework presented in this study allows for a better understanding of complex neural defensive states and their associated functions.
NATURE NEUROSCIENCE
(2023)
Article
Anesthesiology
Mehnaz Ferdousi, Patricia Calcagno, Morgane Clarke, Sonali Aggarwal, Connie Sanchez, Karen L. Smith, David J. Eyerman, John P. Kelly, Michelle Roche, David P. Finn
Summary: Chronic pain often coexists with anxiety and depression, impacting therapeutic outcomes. The role of endogenous mu-opioid receptor system and genetic background in chronic pain are poorly understood. Wistar-Kyoto rats show decreased responsiveness to morphine, suggesting a deficit in the descending inhibitory pain pathway that may underlie hyperalgesia in this genetically predisposed strain.
Article
Multidisciplinary Sciences
Julia Ruat, Andreas J. Genewsky, Daniel E. Heinz, Sebastian F. Kaltwasser, Newton S. Canteras, Michael Czisch, Alon Chen, Carsten T. Wotjak
Summary: A study found that mice with high anxiety-related behavior emit audible calls, which are sensitive to anxiolytics and controlled by the activity of the periaqueductal gray. These calls can attract both predators and conspecifics, depending on the context.
Article
Neurosciences
Zhenhua Jiang, Qun Wang, Jianshuai Zhao, Jiajia Wang, You Li, Wei Dai, Xiao Zhang, Zongping Fang, Wugang Hou, Lize Xiong
Summary: Sex differences in the analgesic effects of cannabinoids were investigated in mice, and it was found that females exhibited stronger analgesia compared to males. This difference was attributed to the higher expression of GABAergic CB(1)Rs in the vlPAG in females. Activation of CB(1)Rs in the vlPAG also reduced GABA-mediated inhibitory currents more significantly in females. These findings suggest that GABAergic CB(1)Rs in the vlPAG modulate cannabinoid-mediated analgesia in a sex-specific manner.
JOURNAL OF COMPARATIVE NEUROLOGY
(2022)
Article
Neurosciences
Olga A. Lyubashina, Ivan B. Sivachenko, Aleksandr A. Mikhalkin
Summary: The study reveals that colonic inflammation alters the functioning of the midbrain periaqueductal gray (PAG), leading to impaired control of visceral nociception. This dysfunction in ascending and descending pathways may contribute to visceral hyperalgesia associated with gut injury.
BRAIN RESEARCH BULLETIN
(2022)
Article
Physiology
Gustavo Henrique de Mello Rosa, Farhad Ullah, Yara Bezerra de Paiva, Juliana Almeida da Silva, Luiz Guilherme S. Branco, Alexandre Pinto Corrado, Priscila Medeiros, Norberto Cysne Coimbra, Audrey Franceschi Biagioni
Summary: Defensive immobility is an adaptive response in rodents during unavoidable threats, regulated by the ventrolateral periaqueductal gray matter (vlPAG) and associated with changes in pain perception and breathing. Chemical stimulation of vlPAG induces defensive immobility and alters respiratory responses.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Article
Neurosciences
Xixiao Zhu, Yingling Xu, Zui Shen, Haiyan Zhang, Siqi Xiao, Yichen Zhu, Mengwei Wu, Yeqing Chen, Zemin Wu, Yunyun Xu, Xiaofen He, Boyu Liu, Jinggen Liu, Junying Du, Jing Sun, Jianqiao Fang, Xiaomei Shao
Summary: This study revealed a novel pathway, the rACC(Glu)-vIPAG pathway, which mediates neuropathic pain and pain-induced anxiety. The activation and inhibition of this pathway were found to have effects on hyperalgesia and anxiety-like behaviors using chemogenetic methods and electroacupuncture therapy.
FRONTIERS IN NEUROSCIENCE
(2022)
Editorial Material
Clinical Neurology
Nandakumar S. Narayanan, Faheem Sheriff, John M. Boyce
Article
Clinical Neurology
Jordan L. Schultz, Alivia N. Brinker, Jia Xu, Sarah E. Ernst, Fariba Tayyari, Adam J. Rauckhorst, Lei Liu, Ergun Y. Uc, Eric B. Taylor, Jacob E. Simmering, Vincent A. Magnotta, Michael J. Welsh, Nandakumar S. Narayanan
Summary: This 12-week pilot study in people with PD suggests that terazosin may engage its target and increase ATP levels in the brain and blood. However, mild dizziness/lightheadedness was more common in the terazosin group, leading to dropouts in some participants. Further studies are needed to explore the disease-modifying potential of terazosin.
PARKINSONISM & RELATED DISORDERS
(2022)
Review
Neurosciences
Puja K. Parekh, Shane B. Johnson, Conor Liston
Summary: Depression is characterized by mood state transitions with poorly understood neurobiological mechanisms. Antidepressants reverse the effects of stress and depression on synapse function, suggesting that synaptic remodeling plays a key role in depression pathophysiology and antidepressant function. Antidepressants initially act by facilitating plasticity and reconfiguring the brain state, with synaptogenesis sustaining these changes over time.
ANNUAL REVIEW OF NEUROSCIENCE
(2022)
Article
Behavioral Sciences
Matthew A. Weber, Mackenzie M. Conlon, Hannah R. Stutt, Linder Wendt, Patrick Ten Eyck, Nandakumar S. Narayanan
Summary: Dopamine in the prefrontal cortex has an inverted U-shaped relationship with cognitive function, with optimal dopamine and D1DR signaling being required for peak cognitive function. The relationship explains 10% of the variance in working memory performance. Prefrontal D1DR signaling has a stronger effect, explaining 26% of the variance. These findings provide insights into the dynamics of prefrontal dopamine and have implications for pharmacological interventions and the pathophysiology of brain diseases.
BEHAVIORAL NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Annette Klomp, Ryotaro Omichi, Yoichiro Iwasa, Richard J. Smith, Yuriy M. Usachev, Andrew F. Russo, Nandakumar S. Narayanan, Amy Lee
Summary: Voltage-gated Ca2+ channels play a critical role in the development and function of the nervous system. Mutations in the CACNA2D4 gene, which encodes the alpha(2)delta-4 auxiliary subunit of these channels, are associated with neuropsychiatric and neurodevelopmental disorders. This study investigates the behavioral phenotypes of alpha(2)delta-4 knockout mice and reveals unexpected roles of alpha(2)delta-4 in sensorimotor gating and motor function.
Article
Behavioral Sciences
Travis Larson, Vaibhav Khandelwal, Matthew A. Weber, Mariah R. Leidinger, David K. Meyerholz, Nandakumar S. Narayanan, Qiang Zhang
Summary: Interval timing is a crucial executive process that is impaired in patients with Alzheimer's disease (AD). Studying interval timing tasks in animal models of AD can provide insights into the human disease. This study evaluated the interval timing performance of P301S transgenic mice, a model of tauopathy, and found that they consistently underestimated temporal intervals. This finding may have relevance to human tauopathies such as AD.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Article
Audiology & Speech-Language Pathology
Peter A. Santi, Shane Johnson, Julian Wuester, Matthew Griesbach, Alexander Claussen, Jonathon Kirk
Summary: Postmortem examination of the cochlea with a cochlear implant presents challenges due to the presence of wires and metal components that make sectioning difficult. Plastic embedded implanted cochleas have been successfully sectioned using specialized methods. An alternative non-destructive method is optical sectioning of a chemically cleared cochlea, but the presence of metal components results in artifacts in the 2D optical sections. Removal of the implant prior to imaging yields the best image quality.
Article
Clinical Neurology
Jacob E. Simmering, Michael J. Welsh, Jordan Schultz, Nandakumar S. Narayanan
Summary: This study found that men using terazosin and closely related alpha 1-adrenergic receptor antagonists had a lower risk of developing Parkinson's disease compared to those using tamsulosin or 5 alpha-reductase inhibitors.
MOVEMENT DISORDERS
(2022)
Article
Neurosciences
Gail I. S. Harmata, Aubrey C. Chan, Madison J. Merfeld, Rebecca J. Taugher-Hebl, Anjit K. Harijan, Jason B. Hardie, Rong Fan, Jeffrey D. Long, Grace Z. Wang, Brian J. Dlouhy, Amal K. Bera, Nandakumar S. Narayanan, John A. Wemmie
Summary: Individuals differ in their sensitivity to acute alcohol intoxication, and alcohol effects are complex and may be related to acid-sensing ion channels (ASICs). This study found that ASIC1A plays a role in the intoxicating effects of alcohol, and its absence affects the electrophysiological responses and behavior. These findings suggest that ASICs might contribute to the intoxicating effects of alcohol and AUD in humans.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Shane B. Johnson, Ryan T. Lingg, Timothy D. Skog, Dalton C. Hinz, Sara A. Romig-Martin, Victor Viau, Nandakumar S. Narayanan, Jason J. Radley
Summary: This study explores the link between behavioral and biological features of stress responses in the brain. It identifies the involvement of the medial prefrontal cortex (mPFC) and midbrain dorsolateral periaqueductal gray (PAG) in active stress coping behaviors, while a different circuit involving the rostral mPFC and ventrolateral PAG limits passive behaviors. Furthermore, the activation of the caudal mPFC-dorsolateral PAG projection can attenuate the increase in stress hormone output and immobility associated with a passive coping response. These findings provide insights into how the brain coordinates different responses to stress and contributes to stress resilience.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Peter A. Santi, Shane B. Johnson
Summary: Deafness is a common sensory impairment, particularly in the elderly population. However, studying the relationship between the structure and function of the inner ear has been challenging. To overcome this, researchers have developed a light-sheet microscope that can image and digitize the entire cochlea, enabling a better understanding of its structure and function. Using this technique, researchers were able to quantify the loss of hair cells and spiral ganglion neurons, as well as observe local reductions in spiral ganglion neurons within the cochlea.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Clinical Neurology
Arun Singh, Rachel C. Cole, Arturo Espinoza, Jan R. Wessel, James F. Cavanagh, Nandakumar S. Narayanan
Summary: Cognitive dysfunction in Parkinson's disease is associated with abnormal low-frequency cortical rhythms in the mid-frontal region. These rhythms can predict cognitive impairment in PD and may serve as potential biomarkers and targeted therapies for cognitive symptoms.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Neurosciences
Shana Harris, Nandakumar S. S. Narayanan, Daniel Tranel
Summary: Black patients are diagnosed with Parkinson's disease at a lower rate than White patients, and the reasons for this disparity are unknown. Practitioner bias surrounding facial expressivity in Black patients may lead to misinterpretation of hypomimia as higher levels of facial expressivity and negative personality traits. This bias in the evaluation of hypomimia could significantly impact referral decisions and diagnosis rates. Exploring these differences is crucial for addressing healthcare disparities and improving detection of Parkinson's disease in Black patients.
NPJ PARKINSONS DISEASE
(2023)
Article
Neurosciences
Rachel C. Cole, Arturo Espinoza, Arun Singh, Joel Berger, James F. Cavanagh, Jan R. Wessel, Jeremy D. Greenlee, Nandakumar S. Narayanan
Summary: This study investigates the corticostriatal mechanisms underlying novelty-response deficits in Parkinson's disease (PD) patients. The results suggest that novel auditory stimuli trigger specific low-frequency rhythms, where 1-4 Hz delta rhythms are associated with slowing response and 4-7 Hz theta rhythms are attenuated in PD patients. Moreover, subthalamic nucleus (STN) neurons show response modulation and coherence with midfrontal 1-4 Hz activity, indicating the involvement of hyperdirect frontobasal ganglia circuits in evaluating new information.