@article{pmid39890796,

title = {SIV infection induces alterations in gene expression and loss of interneurons in Rhesus Macaque frontal cortex during early systemic infection},

author = {Richard C Crist and Samar N Chehimi and Saurabh S Divakaran and Michael J Montague and Sébastien Tremblay and Noah Snyder-Mackler and Martin O Bohlen and Kenneth L Chiou and Trish M Zintel and  and Michael L Platt and Halvor Juul and Guido Silvestri and Matthew R Hayes and Dennis L Kolson and Benjamin C Reiner},

doi = {10.1038/s41398-025-03261-2},

issn = {2158-3188},

year  = {2025},

date = {2025-01-01},

journal = {Transl Psychiatry},

volume = {15},

number = {1},

pages = {38},

abstract = {Understanding the neurobiological mechanisms underlying HIV-associated neurocognitive decline in people living with HIV is frequently complicated by an inability to analyze changes across the course of the infection and frequent presence of comorbid psychiatric and substance use disorders. Preclinical non-human primate simian immunodeficiency virus (SIV) models help address these shortcomings. However, SIV studies frequently target protracted endpoints, limiting our understanding of the neuromolecular alterations during the early post-infection window. To begin to address this knowledge gap, we utilized single nuclei transcriptomics to examine frontal cortex samples of rhesus macaques 10- and 20-days post-SIV infection, compared to non-infected controls. We identify and validated a decrease in inhibitory neurons during the early post infection window, representing a potential substrate of longer-term injury and neurocognitive impairment in people living with HIV. Differential expression identified alterations in cellular subtype gene expression that persisted over the 20-day time course and short-lived differences only detected at 10-days post-SIV infection. In silico predicted regulatory mechanisms and dysregulated neural signaling pathways are presented. Analysis of cell-cell interaction networks identify altered signal pathways in the frontal cortex that may represent regional alterations in cell-cell communications. In total, these results identify cell type-specific molecular mechanisms putatively capable of underlying long-term neurocognitive alterations in persons living with HIV.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Farinas2024,

title = {Mapping Nociceptive and Opioidergic Cell-Types in the Cingulate Cortex of Mice and Non-Human Primates},

author = {Sofia A. Farinas and Gregory Salimando and Sebastien Tremblay and Jacqueline W.K. Wu and Lisa Wooldridge and Nora McCall and Michael L. Platt and Charu Ramakrishnan and Karl Deisseroth and Gregory Corder},

doi = {10.1016/j.jpain.2024.01.081},

issn = {1526-5900},

year  = {2024},

date = {2024-04-16},

urldate = {2024-11-12},

journal = {The Journal of Pain},

volume = {25},

number = {4},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38480888,

title = {Neural signatures of natural behaviour in socializing macaques},

author = {Camille Testard and Sébastien Tremblay and Felipe Parodi and Ron W DiTullio and Arianna Acevedo-Ithier and Kristin L Gardiner and Konrad Kording and Michael L Platt},

doi = {10.1038/s41586-024-07178-6},

issn = {1476-4687},

year  = {2024},

date = {2024-04-01},

journal = {Nature},

volume = {628},

number = {8007},

pages = {381--390},

abstract = {Our understanding of the neurobiology of primate behaviour largely derives from artificial tasks in highly controlled laboratory settings, overlooking most natural behaviours that primate brains evolved to produce. How primates navigate the multidimensional social relationships that structure daily life and shape survival and reproductive success remains largely unclear at the single-neuron level. Here we combine ethological analysis, computer vision and wireless recording technologies to identify neural signatures of natural behaviour in unrestrained, socially interacting pairs of rhesus macaques. Single-neuron and population activity in the prefrontal and temporal cortex robustly encoded 24 species-typical behaviours, as well as social context. Male-female partners demonstrated near-perfect reciprocity in grooming, a key behavioural mechanism supporting friendships and alliances, and neural activity maintained a running account of these social investments. Confronted with an aggressive intruder, behavioural and neural population responses reflected empathy and were buffered by the presence of a partner. Our findings reveal a highly distributed neurophysiological ledger of social dynamics, a potential computational foundation supporting communal life in primate societies, including our own.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37824616,

title = {A single-cell multi-omic atlas spanning the adult rhesus macaque brain},

author = {Kenneth L Chiou and Xingfan Huang and Martin O Bohlen and Sébastien Tremblay and Alex R DeCasien and Diana R O'Day and Cailyn H Spurrell and Aishwarya A Gogate and Trisha M Zintel and  and Madeline G Andrews and Melween I Martínez and Lea M Starita and Michael J Montague and Michael L Platt and Jay Shendure and Noah Snyder-Mackler},

doi = {10.1126/sciadv.adh1914},

issn = {2375-2548},

year  = {2023},

date = {2023-10-01},

journal = {Sci Adv},

volume = {9},

number = {41},

pages = {eadh1914},

abstract = {Cataloging the diverse cellular architecture of the primate brain is crucial for understanding cognition, behavior, and disease in humans. Here, we generated a brain-wide single-cell multimodal molecular atlas of the rhesus macaque brain. Together, we profiled 2.58 M transcriptomes and 1.59 M epigenomes from single nuclei sampled from 30 regions across the adult brain. Cell composition differed extensively across the brain, revealing cellular signatures of region-specific functions. We also identified 1.19 M candidate regulatory elements, many previously unidentified, allowing us to explore the landscape of cis-regulatory grammar and neurological disease risk in a cell type-specific manner. Altogether, this multi-omic atlas provides an open resource for investigating the evolution of the human brain and identifying novel targets for disease interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37704594,

title = {Human OPRM1 and murine Oprm1 promoter driven viral constructs for genetic access to μ-opioidergic cell types},

author = {Gregory J Salimando and Sébastien Tremblay and Blake A Kimmey and Jia Li and Sophie A Rogers and Jessica A Wojick and Nora M McCall and Lisa M Wooldridge and Amrith Rodrigues and Tito Borner and Kristin L Gardiner and Selwyn S Jayakar and Ilyas Singeç and Clifford J Woolf and Matthew R Hayes and Bart C De Jonghe and F Christian Bennett and Mariko L Bennett and Julie A Blendy and Michael L Platt and Kate Townsend Creasy and William R Renthal and Charu Ramakrishnan and Karl Deisseroth and Gregory Corder},

doi = {10.1038/s41467-023-41407-2},

issn = {2041-1723},

year  = {2023},

date = {2023-09-01},

journal = {Nat Commun},

volume = {14},

number = {1},

pages = {5632},

abstract = {With concurrent global epidemics of chronic pain and opioid use disorders, there is a critical need to identify, target and manipulate specific cell populations expressing the mu-opioid receptor (MOR). However, available tools and transgenic models for gaining long-term genetic access to MOR+ neural cell types and circuits involved in modulating pain, analgesia and addiction across species are limited. To address this, we developed a catalog of MOR promoter (MORp) based constructs packaged into adeno-associated viral vectors that drive transgene expression in MOR+ cells. MORp constructs designed from promoter regions upstream of the mouse Oprm1 gene (mMORp) were validated for transduction efficiency and selectivity in endogenous MOR+ neurons in the brain, spinal cord, and periphery of mice, with additional studies revealing robust expression in rats, shrews, and human induced pluripotent stem cell (iPSC)-derived nociceptors. The use of mMORp for in vivo fiber photometry, behavioral chemogenetics, and intersectional genetic strategies is also demonstrated. Lastly, a human designed MORp (hMORp) efficiently transduced macaque cortical OPRM1+ cells. Together, our MORp toolkit provides researchers cell type specific genetic access to target and functionally manipulate mu-opioidergic neurons across a range of vertebrate species and translational models for pain, addiction, and neuropsychiatric disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37461580,

title = {Neural signatures of natural behavior in socializing macaques},

author = {Camille Testard and Sebastien Tremblay and Felipe Parodi and Ronald W DiTullio and Arianna Acevedo-Ithier and Kristin Gardiner and Konrad Paul Kording and Michael Platt},

doi = {10.1101/2023.07.05.547833},

issn = {2692-8205},

year  = {2023},

date = {2023-09-01},

urldate = {2023-09-01},

journal = {bioRxiv},

abstract = {Our understanding of the neurobiology of primate behavior largely derives from artificial tasks in highly-controlled laboratory settings, overlooking most natural behaviors primate brains evolved to produce1. In particular, how primates navigate the multidimensional social relationships that structure daily life and shape survival and reproductive success remains largely unexplored at the single neuron level. Here, we combine ethological analysis with new wireless recording technologies to uncover neural signatures of natural behavior in unrestrained, socially interacting pairs of rhesus macaques within a larger colony. Population decoding of single neuron activity in prefrontal and temporal cortex unveiled robust encoding of 24 species-typical behaviors, which was strongly modulated by the presence and identity of surrounding monkeys. Male-female partners demonstrated near-perfect reciprocity in grooming, a key behavioral mechanism supporting friendships and alliances, and neural activity maintained a running account of these social investments. When confronted with an aggressive intruder, behavioral and neural population responses reflected empathy and were buffered by the presence of a partner. Surprisingly, neural signatures in prefrontal and temporal cortex were largely indistinguishable and irreducible to visual and motor contingencies. By employing an ethological approach to the study of primate neurobiology, we reveal a highly-distributed neurophysiological record of social dynamics, a potential computational foundation supporting communal life in primate societies, including our own.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36536242,

title = {Neural cognitive signals during spontaneous movements in the macaque},

author = {Sébastien Tremblay and Camille Testard and Ron W DiTullio and Jeanne Inchauspé and Michael Petrides},

doi = {10.1038/s41593-022-01220-4},

issn = {1546-1726},

year  = {2023},

date = {2023-02-01},

journal = {Nat Neurosci},

volume = {26},

number = {2},

pages = {295--305},

abstract = {The single-neuron basis of cognitive processing in primates has mostly been studied in laboratory settings where movements are severely restricted. It is unclear, therefore, how natural movements might affect neural signatures of cognition in the brain. Moreover, studies in mice indicate that body movements, when measured, account for most of the neural dynamics in the cortex. To examine these issues, we recorded from single-neuron ensembles in the prefrontal cortex in moving monkeys performing a cognitive task and characterized eye, head and body movements using video tracking. Despite considerable trial-to-trial movement variability, single-neuron tuning could be precisely measured and decision signals accurately decoded on a single-trial basis. Creating or abolishing spontaneous movements through head restraint and task manipulations had no measurable impact on neural responses. However, encoding models showed that uninstructed movements explained as much neural variance as task variables, with most movements aligned to task events. These results demonstrate that cognitive signals in the cortex are robust to natural movements, but also that unmeasured movements are potential confounds in cognitive neurophysiology experiments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36424430,

title = {Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment},

author = {Kenneth L Chiou and Alex R DeCasien and Katherina P Rees and Camille Testard and Cailyn H Spurrell and Aishwarya A Gogate and Hannah A Pliner and Sébastien Tremblay and Arianne Mercer and Connor J Whalen and Josué E Negrón-Del Valle and Mareike C Janiak and Samuel E Bauman Surratt and Olga González and Nicole R Compo and Michala K Stock and Angelina V Ruiz-Lambides and Melween I Martínez and  and Melissa A Wilson and Amanda D Melin and Susan C Antón and Christopher S Walker and Jérôme Sallet and Jason M Newbern and Lea M Starita and Jay Shendure and James P Higham and Lauren J N Brent and Michael J Montague and Michael L Platt and Noah Snyder-Mackler},

doi = {10.1038/s41593-022-01197-0},

issn = {1546-1726},

year  = {2022},

date = {2022-12-01},

journal = {Nat Neurosci},

volume = {25},

number = {12},

pages = {1714--1723},

abstract = {Aging is accompanied by a host of social and biological changes that correlate with behavior, cognitive health and susceptibility to neurodegenerative disease. To understand trajectories of brain aging in a primate, we generated a multiregion bulk (N = 527 samples) and single-nucleus (N = 24 samples) brain transcriptional dataset encompassing 15 brain regions and both sexes in a unique population of free-ranging, behaviorally phenotyped rhesus macaques. We demonstrate that age-related changes in the level and variance of gene expression occur in genes associated with neural functions and neurological diseases, including Alzheimer's disease. Further, we show that higher social status in females is associated with younger relative transcriptional ages, providing a link between the social environment and aging in the brain. Our findings lend insight into biological mechanisms underlying brain aging in a nonhuman primate model of human behavior, cognition and health.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tremblay2022,

title = {Epiphenomenal neural activity in the primate cortex},

author = {Sébastien Tremblay and Camille Testard and Jeanne Inchauspé and Michael Petrides},

url = {http://biorxiv.org/lookup/doi/10.1101/2022.09.12.506984},

doi = {10.1101/2022.09.12.506984},

year  = {2022},

date = {2022-09-13},

urldate = {2022-09-13},

journal = {bioRxiv},

publisher = {Cold Spring Harbor Laboratory},

abstract = {<jats:title>Abstract</jats:title><jats:p>When neuroscientists record neural activity from the brain, they often conclude that neural responses observed during task performance are indicative of the functional role of the brain area(s) studied. In humans and nonhuman primates, it is often hard to combine recordings and causal techniques within the same experiment, leaving the possibility that the activity recorded may be epiphenomenal rather than reflecting a specific functional role. Currently, the prevalence of epiphenomenal neural activity in the cortex is unknown. To estimate the extent of such activity in primates, we chronically recorded neural activity in the prefrontal cortex of the same monkeys using the same neural implants during the performance of four different cognitive tasks. The four tasks were carefully selected such that only one of them causally depends on the brain area recorded, as demonstrated by previous double dissociation studies. Using the four most common single neuron analyses methods in the field, we found that the prevalence and strength of neural correlates were just as high across all four tasks, including for the three tasks that do not depend on this brain area. These results suggest that the probability of observing epiphenomenal activity in primate cortex is high, which can mislead investigators relying on neural recording or imaging to map brain function.</jats:p><jats:sec><jats:title>One-Sentence Summary</jats:title><jats:p>Tremblay, Testard and colleagues show that inferring a brain area’s function from neural recordings alone could be misleading.</jats:p></jats:sec>},

howpublished = {bioRxiv},

keywords = {},

pubstate = {published},

tppubtype = {article}

}