Review
Neurosciences
Ayla Arslan
Summary: GABA(A) receptors play a key role in inhibiting the adult brain, with specific subtypes like the delta-subunit-GABA(A) receptors expressed in areas like the hippocampus. These receptors, containing the delta subunit, have integrative roles in network oscillations, adding complexity to the understanding of their functions.
JOURNAL OF INTEGRATIVE NEUROSCIENCE
(2021)
Review
Neurosciences
Yu Sun, Zechun Peng, Xiaofei Wei, Nianhui Zhang, Martin Wallner, Istvan Mody, Carolyn R. Houser
Summary: The decreased expression of the delta subunit of the GABA(A) receptor has been found to be associated with altered modulation of tonic inhibition in dentate granule cells in animal models of epilepsy and other disorders. This study aimed to investigate if viral transfection of delta subunits could restore network excitability in a mouse model of epilepsy. The results showed that transfection of delta subunits increased delta subunit expression, downregulated other GABA(A) receptor subunits, and restored more normal network excitability.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Neurosciences
Czarina Ramos, Stefano Lutzu, Miwako Yamasaki, Yuchio Yanagawa, Kenji Sakimura, Susumu Tomita, Masahiko Watanabe, Pablo E. Castillo
Summary: This study provides the first direct evidence of functional extrasynaptic kainate receptors (KARs) on mossy cells (MCs) in the hippocampus. These KARs are mainly located extrasynaptically and play a critical role in the activity of MCs. Increases in ambient glutamate can activate the KARs on MCs.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Cell Biology
Meredith Lodge, Maria-Clemencia Hernandez, Jan M. Schulz, Josef Bischofberger
Summary: GABA can depolarize immature neurons and inhibit AP firing in adult neurogenesis. Different interneuron subtypes mediate GABAergic inputs in newborn hippocampal granule cells, with young neurons showing nonlinear voltage dependence with increasing conductance. The opening of α5-GABA(A)Rs in young neurons is crucial for the inhibition of AP firing and generation of balanced and sparse firing activity.
Article
Multidisciplinary Sciences
Yi Zhou, Yijing Su, Shiying Li, Benjamin C. Kennedy, Daniel Y. Zhang, Allison M. Bond, Yusha Sun, Fadi Jacob, Lu Lu, Peng Hu, Angela N. Viaene, Ingo Helbig, Sudha K. Kessler, Timothy Lucas, Ryan D. Salinas, Xiaosong Gu, H. Isaac Chen, Hao Wu, Joel E. Kleinman, Thomas M. Hyde, David W. Nauen, Daniel R. Weinberger, Guo-li Ming, Hongjun Song
Summary: This study identified molecular characteristics of immature dentate granule cells (imGCs) in the adult human hippocampus using single-nucleus RNA sequencing, revealing common molecular hallmarks across the lifespan and age-dependent transcriptional dynamics. The study also showed a decreased number of imGCs in Alzheimer's disease and demonstrated neurogenesis in the adult human hippocampus.
Article
Biology
Nicholas P. Vyleta, Jason S. Snyder
Summary: Adult-born granule neurons in the hippocampus exhibit enhanced excitability and plasticity during immature stages, which is believed to contribute to their unique roles in learning and memory. Our findings reveal hyper-excitability in the presynaptic terminals of mossy fibers onto CA3 pyramidal neurons, and suggest rapid functionality in immature neurons. Electrophysiological recordings in mouse hippocampal slices demonstrate faster maturation of action potential waveforms in the presynaptic bouton of adult-born granule neurons compared to the soma.
COMMUNICATIONS BIOLOGY
(2023)
Article
Clinical Neurology
Risa Yamazaki, Dianru Wang, Anna De Laet, Renato Maciel, Claudio Agnorelli, Sebastien Cabrera, Sebastien Arthaud, Paul-Antoine Libourel, Patrice Fort, Hyunsook Lee, Pierre-Herve Luppi
Summary: The study aimed to investigate the reactivation of neurons in the hippocampus and supramammillary nucleus during wakefulness and paradoxical sleep. The results showed different activated neurons in these regions during wakefulness and paradoxical sleep, and the activation of granule cells in the infrapyramidal blade of the DG during paradoxical sleep. Further research is needed to determine the role of these granule cells in memory reactivation during paradoxical sleep.
Article
Clinical Neurology
Risa Yamazaki, Dianru Wang, Anna De Laet, Renato Maciel, Claudio Agnorelli, Sebastien Cabrera, Sebastien Arthaud, Paul-Antoine Libourel, Patrice Fort, Hyunsook Lee, Pierre-Herve Luppi
Summary: The study aimed to determine whether the same neurons were reactivated in the hippocampus and the supramammillary nucleus when mice were exposed to different periods of wakefulness and paradoxical sleep. The results showed that different neurons were activated during wakefulness and paradoxical sleep in the two brain regions, with granule cells of the infrapyramidal blade of the DG specifically activated during paradoxical sleep. Further experiments are needed to confirm if these granule cells are involved in memory engrams during paradoxical sleep.
Review
Neurosciences
Tasuku Araki, Yuji Ikegaya, Ryuta Koyama
Summary: Hippocampal neurogenesis continues throughout life and is tightly controlled by environmental conditions, with microglia and astrocytes playing key roles in modulating the process. Glial cells release factors that support adult neurogenesis under normal conditions, but can also contribute to inflammation and hinder neurogenesis in diseases like Alzheimer's, depression, and epilepsy.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Milad Afrasiabi, Akshay Gupta, Huaying Xu, Bogumila Swietek, Vijayalakshmi Santhakumar
Summary: This study reveals that fast-spiking parvalbumin interneurons (PV-INs) contribute minimally to basal synaptic inhibition but selectively mediate sustained feedback inhibition in a subtype of dentate projection neurons called semilunar granule cells (SGCs). The blunting of activity-driven sustained inhibitory gating in SGCs may play a crucial role in their preferential and persistent recruitment during behavioral tasks.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Erin R. Cullen, Kamran Tariq, Amy N. Shore, Bryan W. Luikart, Matthew C. Weston
Summary: This study found that although mTORC2 inactivation can partially rescue morphologic and electrophysiological abnormalities caused by PTEN loss, it is unable to prevent seizures. Further research demonstrated that mTORC2 inactivation, while rescuing dendritic arbor overgrowth, increases synaptic strength and causes impairments in presynaptic function. These results suggest that an increase in excitatory connectivity and co-occurring synaptic dysfunction, even in the absence of morphologic changes, is sufficient to generate seizures downstream of PTEN loss.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Cell Biology
Matias Mugnaini, Mariela F. Trinchero, Alejandro F. Schinder, Veronica C. Piatti, Emilio Kropff
Summary: Optogenetic activation experiments in mice reveal that young adult-born granule cells play a unique role in remodeling spatial maps in the hippocampus, while mature adult-born granule cells do not have this ability.
Article
Cell Biology
Birgit Kriener, Hua Hu, Koen Vervaeke
Summary: This study investigates the role of dendrites in network oscillations in gamma frequency band. The researchers find that the slope of the dendritic input-output relationship in parvalbumin-expressing basket cells is exceptionally low, thereby reducing the cell's sensitivity to changes in its input. Simulation experiments further demonstrate that the low gain is crucial for increasing spike synchrony in basket cell assemblies.
Review
Biochemistry & Molecular Biology
Angela Kecskes, Boldizsar Czeh, Miklos Kecskes
Summary: This review summarizes the role of mossy cells in healthy and overexcited hippocampus, discussing the controversy surrounding their involvement in temporal lobe epilepsy.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Article
Cell & Tissue Engineering
Ya-Dong Li, Yan-Jia Luo, Ling Xie, Dalton S. Tart, Ryan N. Sheehy, Libo Zhang, Leon G. Coleman, Xian Chen, Juan Song
Summary: Patients with Alzheimer's disease (AD) show memory loss, depression, and anxiety, along with impaired adult hippocampal neurogenesis (AHN). This study demonstrates that optogenetic stimulation of the hypothalamic supramammillary nucleus (SuM) enhances AHN in AD mouse models, improving memory and emotion deficits. Activation of SuM-enhanced adult-born neurons (ABNs) triggers synaptic plasticity and microglia phagocytosis, providing insights into the signaling mechanisms involved.
Article
Substance Abuse
Gregg E. Homanics
Review
Substance Abuse
Gregory R. Rompala, Gregg E. Homanics
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2019)
Article
Multidisciplinary Sciences
Mathieu Nollet, Harriet Hicks, Andrew P. McCarthy, Huihai Wu, Carla S. Moller-Levet, Emma E. Laing, Karim Malki, Nathan Lawless, Keith A. Wafford, Derk-Jan Dijk, Raphaelle Winsky-Sommerer
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Substance Abuse
Gregory R. Rompala, Carolyn Ferguson, Gregg E. Homanics
Article
Neurosciences
S. Gallegos, L. San Martin, A. Araya, D. M. Lovinger, G. E. Homanics, L. G. Aguayo
Summary: The alpha 2 subunit of the inhibitory glycine receptor is important for enhancing GlyRs in the adult brain, potentially leading to reduced sedation and increased ethanol consumption.
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Clinical Neurology
C. M. Holton, N. Hanley, E. Shanks, P. Oxley, A. McCarthy, B. J. Eastwood, T. K. Murray, A. Nickerson, K. A. Wafford
ALZHEIMERS RESEARCH & THERAPY
(2020)
Article
Neurosciences
Delia Belelli, Derk Hogenkamp, Kelvin W. Gee, Jeremy J. Lambert
NEUROBIOLOGY OF STRESS
(2020)
Article
Neurosciences
Richa S. Rathod, Carolyn Ferguson, Amit Seth, Annalisa M. Baratta, Sonja L. Plasil, Gregg E. Homanics
Article
Neurosciences
Caterina Montani, Carola Canella, Adam J. Schwarz, Jennifer Li, Gary Gilmour, Alberto Galbusera, Keith Wafford, Daniel Gutierrez-Barragan, Andrew McCarthy, David Shaw, Karen Knitowski, David McKinzie, Alessandro Gozzi, Christian Felder
Summary: The cholinergic drug xanomeline, acting at M1/M4 muscarinic receptors, induces widespread functional activity changes in the rodent brain, including decreased connectivity in the neocortex and striatum, and increased functional connectivity within the nucleus accumbens. Moreover, its effects on phencyclidine and ketamine suggest a modulatory role in specific functional networks within the brain.
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Alexander G. Figueroa, Claudia Benkwitz, Gabe Surges, Nicholas Kunz, Gregg E. Homanics, Robert A. Pearce
Summary: This study found that a specific genetic mutation in mice can resist the inhibitory effects of the general anesthetic etomidate on the formation of new memories. Furthermore, the research suggests that different subunits of GABA(A) receptors play important roles in controlling long-term potentiation and inhibiting neuronal activity. These findings have implications for understanding how anesthetics block memory formation and how inhibitory circuits regulate learning and memory.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Andrew P. McCarthy, Kjell A. Svensson, Elaine Shanks, Claire Brittain, Brian J. Eastwood, William Kielbasa, Kevin M. Biglan, Keith A. Wafford
Summary: This study provides the first translational evidence of the effects of a selective dopamine receptor 1 positive allosteric modulator (D1PAM) on sleep and wakefulness in both humanized dopamine receptor 1 mice and sleep-deprived healthy male volunteers. The findings suggest that sleep-wake activity can serve as a translational biomarker for D1PAM and that D1PAMs may have therapeutic potential for sleep disorders and excessive daytime sleepiness associated with neurodegenerative disorders.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
Melanie J. Grubisha, Tao Sun, Leanna Eisenman, Susan L. Erickson, Shinnyi Chou, Cassandra D. Helmer, Melody T. Trudgen, Ying Ding, Gregg E. Homanics, Peter Penzes, Zachary P. Wills, Robert A. Sweet
Summary: The study demonstrates that the development of neuronal dendrites is regulated by the Nogo receptor 1 pathway, which is stimulated by OMGp and requires the Rho guanine nucleotide exchange factor Kalirin-9. The research also shows that a missense mutation in the Kalrn gene identified in a schizophrenia cohort may lead to abnormal neuronal dendritic function, affecting the perception of gap durations in sound.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Paula de Oliveira, Claire Cella, Nicolas Locker, Kiran K. G. Ravindran, Agampodi Mendis, Keith Wafford, Gary Gilmour, Derk-Jan Dijk, Raphaelle Winsky-Sommerer
Summary: This study investigated the effects of trazodone on cellular pathways and behavioral features of tauopathies in mice. The results showed that trazodone reduced neuroinflammation and unfolded protein response, improved sleep quality and memory performance. These findings provide preliminary evidence for the potential therapeutic value of sleep-modulating compounds in the treatment of tauopathies.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Substance Abuse
Annalisa M. Baratta, Regina A. Mangieri, Heather C. Aziz, Marcelo F. Lopez, Sean P. Farris, Gregg E. Homanics
Summary: Extracellular vesicles (EVs) play important roles in cellular and molecular processes. This study reveals that chronic ethanol exposure significantly alters the RNA cargo of brain-derived EVs, which may impact neuronal function.
Article
Neurosciences
Erik Beeler, Zachary L. Nobile, Gregg E. Homanics