bioRxiv : the preprint server for biology
August 13, 2026
David S Jacobs, Alejandro Torrado Pacheco, Randall Olson et al.
preprint
Emerging clinical research with psilocybin highlights the value of the psychedelic experience on successful treatment of a multitude of psychiatric disorders. While the psychedelic trip or clinical support procedures cannot be modeled in rodents, neural processes critical to meta-learning and flexible modification of previously learned strategies can be quantified during psilocybin exposure....
bioRxiv : the preprint server for biology
August 4, 2026
Kanchan Sinha Roy, Payton Martinez, Sedona N Ewbank et al.
preprint
The psychiatric utility of ketamine is limited by its dissociative and systemic side effects. Recently, to enable precision ketamine pharmacotherapy, we introduced SonoKet, ketamine-loaded acoustically activatable liposomes that enable focused ultrasound (FUS)-targeted ketamine delivery to millimeter-sized brain regions. In initial studies, we observed that SonoKet uncaging targeted ketamine to...
bioRxiv : the preprint server for biology
June 18, 2026
Jacob J. Baker, Emily Kogan, Shaorong Ma et al.
It is unclear how serotonin 2A receptors (5-HT 2A Rs) in cortical layer 5 pyramidal neurons (L5 PyrNs) differentially contribute to psilocybin-induced hallucinations versus neuroplasticity. Here we show that psilocybin promotes synapse formation and maturation while accelerating the elimination of pre-existing synapses. Cell type-specific manipulation further demonstrated that 5-HT 2A R...
bioRxiv : the preprint server for biology
June 12, 2026
Timothy Lawn, Johan Nakuci, Steve Cr Williams et al.
Analyses of neuroimaging data increasingly leverage the distribution of neurotransmitter receptors derived from Positron Emission Tomography (PET) to bridge the gap between micro- and macro-scale brain function. However, these receptor maps are highly spatially overlapping which can give rise to interpretive and analytical challenges. Here, we systematically investigate the impact of spatial...
bioRxiv : the preprint server for biology
June 1, 2026
Panagiotis Fotiadis, Hyunwoo Jang, Rui Dai et al.
Brain waves are ubiquitous phenomena of human brain activity. As they propagate, they coordinate neural communication, shaping conscious perception. Understanding how brain waves unfold across space and time is thus critical for uncovering the neural mechanisms that support and suppress consciousness. Here, we analyzed data from the Human Connectome Project alongside multiple independent human...
bioRxiv : the preprint server for biology
May 26, 2026
Joel I Berger, Matthew I Banks, Emily R Dappen et al.
preprint
Although much is known about the molecular and cellular effects of general anesthetics, the neural mechanisms underlying loss and recovery of consciousness during anesthesia remain elusive. We provide the first report of human single neuron activity recorded throughout emergence from general anesthesia. Following cessation of propofol infusion, emergence was assessed as motor response to verbal...
bioRxiv : the preprint server for biology
May 12, 2026
Tiara Bounyarith, David Braun, Aaron Kucyi
Much of a typical individual's mental life is characterized by spontaneous thoughts that occur independently of external stimuli. In prior studies, ongoing mental experiences and their neural correlates have been captured using thought probes presented at random intervals during functional Magnetic Resonance Imaging (fMRI). However, this approach results in temporally imprecise estimates of...
bioRxiv : the preprint server for biology
May 11, 2026
Jared Plotkin, Elaine Zhu, Mélanie Druart et al.
Psychedelics produce long-lasting effects, but their circuit mechanisms remain unclear. Here we show that, in rats, a single dose of lysergic acid diethylamide (LSD) persistently reduces pain affect. This effect is recapitulated by local administration in the anterior cingulate cortex (ACC), but not primary somatosensory cortex. Neuropixels recordings reveal that LSD suppresses stimulus-evoked...
bioRxiv : the preprint server for biology
April 22, 2026
Cory A. Knox, Samuel C Woodburn, Amelia D. Gilbert et al.
The classic psychedelic psilocybin elicits long-lasting neural plasticity and behavioral effects, but prior studies largely examined stress-naive animals. Using longitudinal imaging, we show that psilocybin increases dendritic spine density in frontal cortical neurons and facilitates fear extinction after chronic restraint stress, demonstrating psilocybin's effects in a translationally relevant...
bioRxiv : the preprint server for biology
April 21, 2026
Jeanine Yacoub, Elena Bray, Jude Bayyat et al.
Serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) and 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin) show therapeutic promise for psychiatric and neurodegenerative disorders but may be limited by liabilities from serotonin (5-HT)-2A mediated psychoactive effects and potential cardiotoxicity via 5-HT2B activation. To address these limitations, we designed and synthesized...
bioRxiv : the preprint server for biology
April 17, 2026
Pasha A. Davoudian, Quan Jiang, Cory A. Knox et al.
Psychedelics show therapeutic potential for treating psychiatric disorders. While studies have emphasized the roles of cortical pyramidal cells, GABAergic neurons also express serotonin receptors and are therefore likely targets of psychedelics. In this study, we determine the effect of psilocybin on the activity dynamics of major GABAergic cell types in the mouse medial frontal cortex....
bioRxiv : the preprint server for biology
March 27, 2026
James D. Johnson, Runyi Tian, Yasaman Etemadi et al.
Psilocybin can produce sustained benefits in affective and trauma-related disorders, yet if and how it reshapes sensory representations of learned valence associations remains largely unclear. To address this, we used longitudinal two-photon calcium imaging in awake C57BL/6 mice to examine how psilocybin modulates layer 2/3 auditory cortex activity at single-cell and population levels. Evoked...
bioRxiv : the preprint server for biology
March 6, 2026
Natasha E Wade, Ryan M Sullivan, Alexander L. Wallace et al.
Adolescents experience extensive neurocognitive development, with cannabis use potentially impacting developmental trajectories. Here, we comprehensively assess the influence of adolescent cannabis use onset on neurocognitive trajectories and consider how recent delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) may influence neurocognition. We use the large, diverse longitudinal...
bioRxiv : the preprint server for biology
January 24, 2026
Kwang-Hyun Hur, Lisa D Nickerson, Jack Bergman et al.
Δ 9 -tetrahydrocannabinol (THC)-containing products are widely used recreationally, partly due to THC's ability to enhance the appetitive (i.e., rewarding) properties of diverse stimuli. However, the neural mechanisms through which THC modulates reward-related processing remain poorly understood. Here, we used a Pavlovian paradigm in adult squirrel monkeys (3males, 1female) to associate a...
bioRxiv : the preprint server for biology
January 22, 2026
Margareth Nogueira, Giuseppe Giannotti, Carley N Miller et al.
Opioid use disorder remains a major health challenge worldwide. Neuronal activity in the ventral pallidum (VP) regulates opioid reward and relapse to opioid seeking but the underlying cellular mechanisms remain largely unknown. A sizable population of VP neurons previously linked to drug relapse expresses the calcium binding protein parvalbumin (VP PV ). Across the brain parvalbumin neurons are...
bioRxiv : the preprint server for biology
January 16, 2026
Fernanda Daher, Caio T Fukushima, Erik A Ingebretsen et al.
1 citation
Chronic stress disrupts glutamatergic and GABAergic plasticity in the medial prefrontal cortex (mPFC), impairing circuit integration and contributing to the pathophysiology of stress-related disorders, such as Major Depressive Disorder (MDD). Rapid-acting antidepressants like ketamine can rapidly reverse these deficits, but its clinical use is limited by psychotomimetic side effects. Notably,...
bioRxiv : the preprint server for biology
January 14, 2026
Teppei Matsubara, Abbas Sohrabpour, Seppo Ahlfors et al.
The cerebellum is increasingly recognized as a key component of large-scale brain networks implicated in epilepsy, yet its electrophysiological characterization remains limited in noninvasive recordings. This limitation arises from the cerebellum's depth, complex folding, and unfavorable source orientations, which challenge conventional magnetoencephalography (MEG) and electroencephalography...
bioRxiv : the preprint server for biology
December 5, 2025
Zev E Jarrett, Brad A Grueter
preprint
Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid constituent of the cannabis plant that shows promise for the treatment of a variety of neuropsychiatric disorders such as anxiety disorders, post-traumatic stress disorder, and substance use disorders. The nucleus accumbens (NAc) is a key brain region in the etiologies of these disorders and is actively modulated by CBD. Prior research...
bioRxiv : the preprint server for biology
November 26, 2025
Sandra M. Martin-Guerrero, Marco Taddei-Tardón, Jessica L Maltman et al.
preprint
Psychedelic drugs can induce intense changes in perception and thought, and some also promote long-lasting adaptations in brain circuits that are being explored for treatment of mood and anxiety disorders. How these compounds differ at the level of intracellular signalling, and how hallucinogenic drugs diverge from related non-hallucinogenic forms, is poorly understood. A central question is...
bioRxiv : the preprint server for biology
November 13, 2025
Winson F.z. Yang, Ruby M. Potash, Grace Mackin et al.
preprint
Humans can experience a rich array of conscious experience, including highly stable, positive, and refined states of non-ordinary perception that can be elicited through advanced meditation. Here, we present the first group-level, ultra-high-field (7T) fMRI study of jhana advanced concentration absorption meditation (ACAM-J). We combined local (regional homogeneity), mesoscale (connectivity...
bioRxiv : the preprint server for biology
November 8, 2025
Lucie Berkovitch, Alexandre Salvador, Thomas Andrillon et al.
preprint
Ketamine is an NMDA-receptor antagonist, which alters the state of wakeful consciousness at high doses. At lower doses, it induces reversible psychotic-like symptoms and has been used as a pharmacological model of psychosis. In this study, we explore whether low doses of ketamine disrupt conscious access in relation with its psychotomimetic effects, and investigate the neural correlates of its...
bioRxiv : the preprint server for biology
October 15, 2025
Rolf J. Skyberg, Christopher W Fields, Dylan M. Martins et al.
preprint
Psychedelic compounds have the ability to generate altered states of consciousness and profoundly distort perception, often resulting in visual hallucinations. While psychedelics have recently regained attention for their potential cognitive and therapeutic effects, how these drugs affect visual processing to generate visual distortions and hallucinations is not as well characterized....
bioRxiv : the preprint server for biology
October 7, 2025
Stefan Sumsky, Rory Ashmeade, Jiayang Liu et al.
preprint
Absence epilepsy is marked by sudden lapses in consciousness accompanied by spike-wave discharges (SWDs), yet the neural mechanisms underlying impaired sensorimotor processing in these episodes remain unresolved. Prior work has shown that normal-appearing signals can persist in primary sensory cortical areas during seizures, suggesting that impaired behavioral responsiveness may arise from...
bioRxiv : the preprint server for biology
September 30, 2025
Ya'El Courtney, Josephine M Anderson, Christian Lagares-Linares et al.
preprint
Despite increasing non-medical use and clinical investigation of psychedelics, the consequences of prenatal exposure remain unknown. In mice, maternal lysergic acid diethylamide (LSD; 0.3 mg kg -1 ) crossed the placenta, appearing in embryonic cerebrospinal fluid (CSF) within minutes at E12.5 and E16.5. Within 30 minutes, LSD and other serotonergic psychedelics induced a 5-HT 2 C agonist-like...
bioRxiv : the preprint server for biology
September 21, 2025
Johanna Rehn, Lucas Admeus, Bernat Kocsis
preprint
The Cannabinoid 1-receptor (CB1R) is found in particularly high levels in the hippocampus (HPC), increased CB1R density and binding observed in patients with schizophrenia, and epidemiological studies suggest that regular cannabis use during adolescence is a risk factor for the disease. Historically, concerns around adolescent marijuana use focused on the development of psychosis later in life,...