Nature
June 1, 2025
Ling-Xiao Shao, Clara Liao, Pasha A. Davoudian et al.
75 citations
Psilocybin is a serotonergic psychedelic with therapeutic potential for treating mental illnesses1-4. At the cellular level, psychedelics induce structural neural plasticity5,6, exemplified by the drug-evoked growth and remodelling of dendritic spines in cortical pyramidal cells7-9. A key question is how these cellular modifications map onto cell-type-specific circuits to produce the...
bioRxiv (Cold Spring Harbor Laboratory)
November 3, 2024
Ling-Xiao Shao, Clara Liao, Pasha A. Davoudian et al.
preprint
Abstract Psilocybin is a serotonergic psychedelic with therapeutic potential for treating mental illnesses 1–4 . At the cellular level, psychedelics induce structural neural plasticity 5,6 , exemplified by the drug-evoked growth and remodeling of dendritic spines in cortical pyramidal cells 7–9 . A key question is how these cellular modifications map onto cell type-specific circuits to produce...
Proceedings for Annual Meeting of The Japanese Pharmacological Society
2022
Ryota Shinohara, Brendan Hare, Rong-Jian Liu et al.
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is the prototype for a potential new generation of glutamate-based antidepressants that rapidly relieve symptoms of depression within hours of treatment. Studies in rodents have demonstrated that neuroplasticity in the medial prefrontal cortex (mPFC) is critical for the antidepressant actions of ketamine. However, effector circuits...
Journal of Clinical Investigation
November 19, 2019
Danielle M. Gerhard, Santosh Pothula, Rong-Jian Liu et al.
345 citations
A single sub-anesthetic dose of ketamine, an NMDA receptor (NMDAR) antagonist, produces rapid and sustained antidepressant actions in depressed patients, addressing a major unmet need for the treatment of mood disorders. Ketamine produces a rapid increase in extracellular glutamate and synaptic formation in the prefrontal cortex, but the initial cellular trigger that initiates these and its...
Neurobiology of Disease
November 7, 2019
Sriparna Ghosal, Catharine H. Duman, Rong-Jian Liu et al.
94 citations
Dysfunction of medial prefrontal cortex (mPFC) in association with imbalance of inhibitory and excitatory neurotransmission has been implicated in depression. However, the precise cellular mechanisms underlying this imbalance, particularly for GABAergic transmission in the mPFC, and the link with the rapid acting antidepressant ketamine remains poorly understood. Here we determined the...
Journal of Clinical Investigation
April 16, 2019
T. Kato, Santosh Pothula, Rong-Jian Liu et al.
88 citations
Preclinical studies demonstrate that rapid acting antidepressants, including ketamine require stimulation of mTORC1 signaling. This pathway is regulated by neuronal activity, endocrine and metabolic signals, notably the amino acid leucine, which activates mTORC1 signaling via binding to the upstream regulator sestrin. Here, we examined the antidepressant actions of NV-5138, a novel highly...
Nature Communications
January 15, 2019
Brendan Hare, R. Shinohara, Rong-Jian Liu et al.
Impaired function in the medial prefrontal cortex (mPFC) contributes to depression, and the therapeutic response produced by novel rapid-acting antidepressants such as ketamine are mediated by mPFC activity. The mPFC contains multiple types of pyramidal cells, but it is unclear whether a particular subtype mediates the rapid antidepressant actions of ketamine. Here we tested two major subtypes,...
Proceedings of the National Academy of Sciences
December 17, 2018
Kenichi Fukumoto, Manoela V. Fogaça, Rong-Jian Liu et al.
191 citations
Significance A metabolite of ketamine, (2 R ,6 R )-hydroxynorketamine [(2 R ,6 R )-HNK], produces rapid and sustained antidepressant effects in animal models but without the side effects of ketamine. Notably, (2 R ,6 R )-HNK does not block the NMDA receptor, the primary target of ketamine. Here, we demonstrate that the antidepressant effects of (2 R ,6 R )-HNK require activity dependent release...
Neuropharmacology
January 2012
Ronald S Duman, Nanxin Li, Rong-Jian Liu et al.
Currently available medications have significant limitations, most notably low response rate and time lag for treatment response. Recent clinical studies have demonstrated that ketamine, an NMDA receptor antagonist produces a rapid antidepressant response (within hours) and is effective in treatment resistant depressed patients. Molecular and cellular studies in rodent models demonstrate that...
Biological Psychiatry
February 3, 2011
Nanxin Li, Rong-Jian Liu, J. Dwyer et al.
Background Despite widely reported clinical and preclinical studies of rapid antidepressant actions of glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonists, there has been very little work examining the effects of these drugs in stress models of depression that require chronic administration of antidepressants, or the molecular mechanisms that could account for the rapid responses....