Biology subjects

Grandjean, J.

Publications and source records attributed to Grandjean, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Resting state fMRI detects pathological functional brain connectivity in the Ndufs4 knockout mouse model of Leigh syndrome during the pre-symptomatic stage of the disease

Leigh syndrome (LS) is a progressive encephalopathy and generally regarded as the most common inborn mitochondrial disease. Mutations in mitochondrial respiratory complex I are common in patients with LS and a mutational hotspot has been identified in the gene that encodes the NDUFS4 subunit of respiratory complex I. The Ndufs4 knockout mouse (Ndufs4 KO) model of LS closely resembles the phenotypes of LS patients and show like the patient brain lesions when the symptoms are manifested. It is speculated but unproven that brain functional connectivity may precede the onset of symptoms. Therefore, the present study was set out to investigate the progression of brain functional connectives in Ndufs4 KO mice before and after the manifestation of LS-like symptoms using in vivo resting-state functional magnetic resonance imaging (rs-fMRI). Since the brain lesions may be caused by increased reactive oxygen species (ROS) in the brain, we also examined the potential protective effect of KH176, a small molecular for modulating ROS levels, on brain functional connectivity. Rs-fMRI results showed that in Ndufs4 KO mice the functional connectivity of the piriform cortex, motor cortex, barrel cortex, visual cortex, auditory cortex, prefrontal cortex, lateral striatum, ventral striatum cortex and amygdala was increased, starting from the pre-symptomatic stage (middle stage) to the symptomatic stage (late stage) of the disease. KH176 had no effect on the changes in functional connectivity in the mice. In conclusion, these results show that there are abnormalities in functional connectivity in Ndufs4 KO mice during the pre-symptomatic phase of the disease and that KH176 treatment does not modify the connectivity changes.

neuroscience↗

bioRxiv2025

Perfect imperfections: seeking molecular and cellular asymmetries in the mouse brain

Although perfect symmetry is a mathematical ideal, many Bilateria exhibit left-right asymmetries of body, brain and behavior that are adaptive 1-3. In the human brain, various aspects of cognition are lateralized, including language 4 and handedness 5, which rely on left hemisphere dominance in most people. Brain hemispheric specialization can support parallel processing, neural efficiency, and action selection 3,6, while atypical structural or functional asymmetries are often found in neuropsychiatric disorders 7-10. Mice may be useful models for studying brain asymmetry because they show hemispheric differences of structure 11,12 and neurophysiology 13, but the extent to which molecular and cellular differences are involved remains unknown. We applied spatial transcriptomics with single molecule resolution to coronal sections from 31 adult mouse brains, to assess left-right differences of gene expression and cell types. Sections were chosen to capture the hippocampus and auditory cortex, as these two regions have shown the most prior evidence for functional asymmetry 13-15. In the hippocampus, Crhr1 (Corticotropin-Releasing Hormone Receptor 1) was more highly expressed in the pyramidal layers of CA1, CA3 and the dentate gyrus of the left hemisphere compared to the right. In the auditory cortex, three principal components capturing transcriptomic variation showed hemispheric differences, including prominent contributions from genes that have shown associations with human brain asymmetry. Overall cellular density and cell type proportions generally showed no significant hemispheric differences, with Car3 cortical excitatory neurons showing the most laterality. The transcriptional left-right differences that we found may relate to functional asymmetries for learning, memory and hearing. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=195 SRC="FIGDIR/small/675542v1_ufig1.gif" ALT="Figure 1"> View larger version (119K): org.highwire.dtl.DTLVardef@1530502org.highwire.dtl.DTLVardef@16dd244org.highwire.dtl.DTLVardef@107950corg.highwire.dtl.DTLVardef@ca52a3_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIMolecular and cellular basis of functional brain asymmetry is barely known C_LIO_LISpatial transcriptomics with cellular resolution applied to mouse brain coronal sections C_LIO_LIGenes implicated in human brain asymmetry showed hemispheric differences in mice C_LIO_LINo hemispheric differences of cell type abundances C_LI

neuroscience↗

bioRxiv2024

The Hurst exponent as a marker of inhibition in the developing brain

The maturation of inhibitory neurons is crucial for regulating plasticity in developing brains. Previous work using computational models has suggested that the Hurst exponent, the decay in power over frequency, reflects inhibition, but empirical data supporting this link is sparse. Here, we took a cross-species approach to validating the Hurst exponent of fMRI as a marker of inhibition, then characterized the development of the Hurst exponent in childhood. We found significant spatial correlations between the Hurst exponent and ex vivo parvalbumin mRNA expression in human children and adults, and between the Hurst exponent and parvalbumin-positive cell counts in mice. We identified a plateau in the mRNA expression by late childhood, aligning with the Hurst exponent plateau in both humans and rats. In sum, this work suggests that the Hurst exponent can be used to study the development of inhibition in vivo, and in the future, to understand individual differences in plasticity.

neuroscience↗

bioRxiv2024

The Neural Blueprint of Stress Susceptibility: Brain-wide neuronal activity associated with the consequences of stress

Understanding the neurobiological mechanisms of stress susceptibility is key to advancing our insight into stress-related psychopathology like post-traumatic stress disorder (PTSD). Preclinical animal models however typically lack translationally relevant brain readouts. Here, we used a mouse model for severe stress, segregating mice into stress-susceptible and resilient groups. We analyzed and contrasted their whole-brain neuronal activity pre-, peri- and post-stress exposure and compared functional connectivity of the salience (SN), default mode (DMN) and executive control network (lateral cortical network (LCN) in rodents). We found that stress-susceptible mice exhibited pre-existing hyperactivity in the lateral orbital area, a potential risk factor for stress vulnerability, and heightened retrosplenial cortex activity peri- and post-stress, potentially contributing to maladaptive fear memory. Upon stress exposure, susceptible mice showed strong recruitment of visual and memory-related areas, whereas resilient mice displayed marked reductions in retrosplenial activity and increased activation in the agranular insula and ventral striatum. Observations of enhanced intra-SN and SN-DMN connectivity in susceptible mice mirrored those observed in individuals with PTSD. Moreover, susceptible mice displayed aberrant DMN-LCN network pre- and peri-stress. These findings highlight the importance of dynamic network interactions in stress susceptibility and suggest novel brain region targets for (early) intervention.

neuroscience↗

bioRxiv2024

Left-Right Brain-Wide Asymmetry of Neuroanatomy in the Mouse Brain

Left-right asymmetry of the human brain is widespread through its anatomy and function. However, limited microscopic understanding of it exists, particularly for anatomical asymmetry where there are few well-established animal models. In humans, most brain regions show subtle, population-average regional asymmetries in thickness or surface area, alongside a macro-scale twisting called the cerebral petalia in which the right hemisphere protrudes anteriorly past the left. Here, we ask whether neuroanatomical asymmetries can be observed in mice, leveraging 6 mouse neuroimaging cohorts from 5 different research groups ([~]3,500 animals). We found an anterior-posterior pattern of volume asymmetry with anterior regions larger on the right and posterior regions larger on the left. This pattern appears driven by similar trends in surface area and positional asymmetries, with the results together indicating a small brain-wide twisting pattern, similar to the human cerebral petalia. Furthermore, the results show no apparent relationship to known functional asymmetries in mice, emphasizing the complexity of the structure-function relationship in brain asymmetry. By establishing a signature of anatomical brain asymmetry in mice, we aim to provide a foundation for future studies to probe the mechanistic underpinnings of brain asymmetry seen in humans - a feature of the brain with extremely limited understanding. Significance StatementThe human brain shows significant left-right anatomical asymmetry. Understanding its microscopic basis has implications for studies of autism and schizophrenia, evolution, embryonic brain development, and the relationship between structure and function in the brain. One of the biggest challenges to understanding this aspect of the brain is that animal models are limited. Here we show a brain-wide twisting pattern of asymmetry in the mouse brain using over 3,500 animals from six independent cohorts. These findings provide a basis for using mice to interrogate the microscopic underpinnings of anatomical asymmetry in humans and a roadmap for exploring anatomical asymmetry in additional species.

neuroscience↗

bioRxiv2024

Functional-based parcellation of the mouse prefrontal cortex for network perturbation analysis

The prefrontal cortex (PFC) is a region of the brain involved in higher-order cognitive processes such as attention, emotional regulation, and social behavior, making it a hotspot for an ongoing clinical and fundamental research. Importantly, its functionality is intricately interconnected within a wide array of functional networks encompassing multiple other brain areas. However, the delineation of distinct subdivisions within the mouse PFC and their contributions to the broader brain network function remain topics of ongoing debate. In the current study, we used resting-state functional magnetic resonance imaging (rsfMRI) from a large cohort of wildtype animals to derive the functional-connectivity (FC) based parcellation of the mouse PFC with voxel resolution. Our findings indicate the presence of FC-based clusters that deviate from the established anatomical subdivisions within the cingulate and prelimbic areas, while they align in infralimbic and orbital cortices. To further underscore the association of these FC-based clusters with distinct functional networks, we performed network-specific perturbations using chemogenetics in the identified clusters in dorsal PFC and monitor the elicited effects with fMRI (chemo-fMRI). Our recordings revealed that FC perturbations were observed only within the functional networks linked to the targeted clusters and did not spread to neighbouring anatomical areas or functional clusters. We propose that FC-based parcellation is a valuable approach for tracking the impact of external activations and confirming the precise site of activation. O_FIG O_LINKSMALLFIG WIDTH=127 HEIGHT=200 SRC="FIGDIR/small/586664v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@11d4042org.highwire.dtl.DTLVardef@165cb5forg.highwire.dtl.DTLVardef@b0a4aorg.highwire.dtl.DTLVardef@d093c9_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

The universe is asymmetric, the mouse brain too.

Hemispheric brain asymmetry is a basic organizational principle of the human brain and has been implicated in various psychiatric conditions, including autism spectrum disorder. Brain asymmetry is not a uniquely human feature and is observed in other species such as the mouse. Yet, asymmetry patterns are generally nuanced, and substantial sample sizes are required to detect these patterns. In this pre-registered study, we use a mouse dataset from the Province of Ontario Neurodevelopmental Network, which comprises structural MRI data from over 2000 mice, including genetic models for autism spectrum disorder, to reveal the scope and magnitude of hemispheric asymmetry in the mouse. Our findings demonstrate the presence of robust hemispheric asymmetry in the mouse brain, such as larger right hemispheric volumes towards the anterior pole and larger left hemispheric volumes toward the posterior pole, opposite to what has been shown in humans. This suggests the existence of species-specific traits. Further clustering analysis identified distinct asymmetry patterns in autism spectrum disorder models, a phenomenon that is also seen in atypically developing participants. Our study shows potential for the use of mouse models in studying the biological bases of typical and atypical brain asymmetry but also warrants caution as asymmetry patterns seem to differ between humans and mice.

neuroscience↗

bioRxiv2023

Comparing mouse and human cingulate cortex organization using functional connectivity

The subdivisions of the extended cingulate cortex of the human brain are both implicated in a number of high-level behaviors and affected by a range of neuropsychiatric disorders. Its anatomy, function, and response to therapeutics are often studied using non-human animals, including the mouse. However, the similarity of human and mouse frontal cortex, including cingulate areas, is still not fully understood. Some accounts emphasize resemblances between mouse cingulate cortex and human cingulate cortex while others emphasize similarities with human granular prefrontal cortex. We use comparative neuroimaging to study the connectivity of the cingulate cortex in the mouse and human, allowing comparisons between mouse gold standard tracer and imaging data, and, in addition, comparison between the mouse and the human using comparable imaging data. We find overall similarities in organization of the cingulate between species, including anterior and midcingulate areas and a retrosplenial area. However, human cingulate contains subareas with a more fine-grained organization than is apparent in the mouse and it has connections to prefrontal areas not present in the mouse. Results such as these help formally address between-species brain organization with an aim to improve the translation from preclinical to human results.

neuroscience↗

bioRxiv2023

Estimating foraging behavior in rodents using a modified paradigm measuring threat imminence dynamics

Animals display defensive behaviors in response to threats to avoid danger and approach rewards. In nature, these responses did not evolve alone but are always accompanied by motivational conflict. A semi-naturalistic threat imminence continuum model models the approach-avoidance conflict and is able to integrate multiple defensive behaviors into a single paradigm. However, its comprehensive application is hampered by the lack of a detailed protocol and data about some fundamental factors including sex, age, and motivational level. Here, we modified a previously established paradigm measuring threat imminence continuum dynamics, involving modifications of training and testing protocols, and utilization of commercial materials combined with open science codes, making it more standardized and easier to replicate. We demonstrate that foraging behavior is modulated by age, hunger level, and sex. This paradigm can be used to study defensive behaviors in animals in a more naturalistic manner with relevance to human approach-avoid conflicts and associated psychopathologies. HighlightsO_LIWe provide detailed guidance for setting up a modified paradigm for the threat imminence continuum model with commercial materials and open-source codes. C_LIO_LIWe propose a modified paradigm for the threat imminence continuum model to quantify foraging behaviors. C_LIO_LIOur method enables comparison between groups as a function of multiple factors including age and food restriction. C_LI Graphic Summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/550314v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@f4be92org.highwire.dtl.DTLVardef@b7f6dorg.highwire.dtl.DTLVardef@db0dc1org.highwire.dtl.DTLVardef@1640cce_HPS_FORMAT_FIGEXP M_FIG C_FIG

animal behavior and cognition↗

bioRxiv2022

Maternal microbes and early brain development in mouse

The complex symbiotic relationship between the mammalian body and gut microbiome plays a critical role in the health outcomes of offspring later in life. The gut microbiome modulates virtually all physiological functions through direct or indirect interactions to maintain physiological homeostasis. Previous studies indicate a link between maternal/early-life gut microbiome, brain development, and behavioral outcomes relating to social cognition. Here we present direct evidence of the role of the gut microbiome in brain development. Through magnetic resonance imaging (MRI), we investigated the impact of the gut microbiome on brain organization and structure using germ-free (GF) mice and conventionalized mice, with the gut microbiome reintroduced after weaning. We found broad changes in brain volume in GF mice that persist despite the reintroduction of gut microbes at weaning. These data suggest a direct link between the maternal gut or early-postnatal microbe and their impact on brain developmental programming.

neuroscience↗

bioRxiv2022

Rodent Automated Bold Improvement of EPI Sequences (RABIES): A standardized image processing and data quality platform for rodent fMRI.

Functional magnetic resonance imaging (fMRI) in rodents holds great potential for advancing our understanding of brain networks. Unlike the human fMRI community, there remains no standardized resource in rodents for image processing, analysis and quality control, posing significant reproducibility limitations. Our software platform, Rodent Automated Bold Improvement of EPI Sequences (RABIES), is a novel pipeline designed to address these limitations for preprocessing, quality control, and confound correction, along with best practices for reproducibility and transparency. We demonstrate the robustness of the preprocessing workflow by validating performance across multiple acquisition sites and both mouse and rat data. Building upon a thorough investigation into data quality metrics across acquisition sites, we introduce guidelines for the quality control of network analysis and offer recommendations for addressing issues. Taken together, the RABIES software will allow the emerging community to adopt reproducible practices and foster progress in translational neuroscience.

neuroscience↗

bioRxiv2022

TPH2 knockout male rats are aggressive, show less anxiety, and exhibit an altered oxytocin system

The central serotoninergic system is critical for stress responsivity and social behavior, and its dysregulations has been centrally implicated in virtually all neuropsychiatric disorders. Genetic serotonin depletion animal models could provide a tool to elucidate the causes and mechanisms of diseases and to develop new treatment approaches. Previously mice lacking tryptophan hydroxylase 2 (Tph2) have been developed, showing altered behaviors and neurotransmission. However, the effect of congenital serotonin deficiency on emotional and social behavior in rats is still largely unknown, as are the underlying mechanisms. In this study, we used Tph2 knockout (Tph2-/-) male rat model to study how the lack of serotonin in the rat brain affects anxiety-like and social behaviors. Since oxytocin is centrally implicated in these behaviors, we furthermore explored whether effects of Tph2 knockout on behavior would relate to changes in the oxytocin system. We show that Tph2-/- rats display reduced anxiety-like behavior and a high level of aggression in social interactions. In addition, oxytocin receptor expression was increased in the infralimbic and prelimbic cortex, paraventricular nucleus, dorsal raphe nucleus and some subregions of hippocampus, which was paralleled by increased levels of oxytocin in the medial frontal cortex, paraventricular nucleus, but not the dorsal raphe nucleus, central amygdala and hippocampus. In conclusion, our study demonstrated reduced anxiety but exaggerated aggression in Tph2-/- male rats and reveals for the first time a potential involvement of altered oxytocin system function. SIGNIFICANCE STATEMENTWe explored the changes in behavior and oxytocin system functioning in the tryptophan hydroxylase 2 (Tph2) knockout rat model, lacking serotonin in the brain. This rat model contributes to our understanding of the role of serotonin in psychiatric transdiagnostic features and underlying mechanisms. We found that Tph2 knockout male rats are aggressive, less anxious, and exhibit an altered oxytocin system. The observed changes in oxytocin signaling may lead to a new target for the treatment of diseases caused by genetic serotonin deficiency.

neuroscience↗

bioRxiv2022

The evolution of information transmission in mammalian brain networks

Brain communication, defined as information transmission through white-matter connections, is at the foundation of the brains computational capacities that subtend almost all aspects of behavior: from sensory perception shared across mammalian species, to complex cognitive functions in humans. How did communication strategies in macroscale brain networks adapted across evolution to accomplish increasingly complex functions? By applying a graph- and information-theory approach to assess information-related pathways in mouse, macaque and human brains, we show a brain communication gap between selective information transmission in non-human mammals, where brain regions share information through single polysynaptic pathways, and parallel information transmission in humans, where regions share information through multiple parallel pathways. In humans, parallel transmission acts as a major connector between unimodal and transmodal systems. The layout of information-related pathways is unique to individuals across different mammalian species, pointing at the individual-level specificity of information routing architecture. Our work provides evidence that different communication patterns are tied to the evolution of mammalian brain networks.

neuroscience↗

bioRxiv2022

StandardRat: A multi-center consensus protocol to enhance functional connectivity specificity in the rat brain

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows comparison with invasive or terminal procedures. To date, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. We introduce StandardRat, a consensus rat functional MRI acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired in rats from 46 centers. We developed a reproducible pipeline for the analysis of rat data acquired with diverse protocols and determined experimental and processing parameters associated with a more robust functional connectivity detection. We show that the standardized protocol enhances biologically plausible functional connectivity patterns, relative to pre-existing acquisitions. The protocol and processing pipeline described here are openly shared with the neuroimaging community to promote interoperability and cooperation towards tackling the most important challenges in neuroscience.

neuroscience↗

bioRxiv2020

Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the unfolded protein response (UPR) in models of neurodegeneration

Alteration to endoplasmic reticulum (ER) proteostasis is observed on a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteostasis and cell function. The UPR is initiated by specialized stress sensors that engage gene expression programs through the concerted action of the transcription factors ATF4, ATF6f, and XBP1s. Although UPR signaling is generally studied as unique linear signaling branches, correlative evidence suggests that ATF6f and XBP1s may physically interact to regulate a subset of UPR-target genes. Here, we designed an ATF6f-XBP1s fusion protein termed UPRplus that behaves as a heterodimer in terms of its selective transcriptional activity. Cell-based studies demonstrated that UPRplus has stronger an effect in reducing the abnormal aggregation of mutant huntingtin and alpha-synuclein when compared to XBP1s or ATF6 alone. We developed a gene transfer approach to deliver UPRplus into the brain using adeno-associated viruses (AAVs) and demonstrated potent neuroprotection in vivo in preclinical models of Parkinsons and Huntingtons disease. These results support the concept where directing UPR-mediated gene expression toward specific adaptive programs may serve as a possible strategy to optimize the beneficial effects of the pathway in different disease conditions.

neuroscience↗

bioRxiv2020

BDNF Overexpression in the Prelimbic Cortex Does Not Reduce Anxiety- and Depression-like Behavior in Serotonin Knockout Rats

Depressive disorders are one of the leading causes of non-fatal health loss in the last decade. Adding to the burden, the available treatments not always properly work for some individuals. There is, therefore, a constant effort from clinical and preclinical studies to bring forward a better understanding of the disease and look for novel alternative therapies. Two target systems very well explored are the serotonin and the brain-derived neurotrophic factor (BDNF) systems. Selective serotonin reuptake inhibitors (SSRIs), a commonly used class of antidepressants, target the serotonin transporter (SERT) and increase serotonin levels, which in turn also leads to an increase in BDNF. A rat model lacking SERT (SERT knockout) has been a useful tool to study the interplay between serotonin and BDNF. SERT-/- rats present increased extracellular levels of serotonin, yet BDNF levels are decreased, especially in the prefrontal cortex (PFC) and hippocampus. The animals further display anxiety- and depression-like behavior. Therefore, BDNF might mediate the phenotype expressed by the SERT-/- rats. In this study, we sought to investigate whether overexpression of BDNF in the brain of SERT-/- rats would rescue its anxious and depressive-like behavior. Through stereotaxic surgery, SERT-/- and wild-type (WT) rats received BDNF or GFP lentivirus microinfusions into the prelimbic cortex subregion of the mPFC and were submitted to the sucrose consumption, open field test, and forced swim tests. Additionally, we measured hypothalamus-pituitary-adrenal (HPA)-axis reactivity. The results revealed that SERT-/- rats presented decreased sucrose intake, decreased locomotor activity, and increased escape-oriented behavior in the forced swim test compared to WT rats. BDNF upregulation in WT rats caused alterations in the HPA-axis function, resulting in elevated basal plasma corticosterone levels and decreased plasma corticosterone upon stress. In conclusion, BDNF overexpression in the PrL, in general, did not rescue SERT-/- rats from its depression- and anxiety-like behavior, and in WT animals, it caused a malfunction in the HPA-axis.

animal behavior and cognition↗

bioRxiv2020

BDNF overexpression in the ventral hippocampus promotes antidepressant- and anxiolytic-like activity in serotonin transporter knockout rats

Brain-derived neurotrophic factor is one of the most studied proteins playing a pivotal role in neuroplasticity events and vulnerability and resilience to stress-related disorders. Most importantly, BDNF is decreased in depressive patients, and increased after antidepressant treatment. Additionally, BDNF was found to be reduced in a genetic subset of depression susceptible patients carrying the human polymorphism in the serotonin transporter promoter region (5-HTTLPR). The serotonin knockout rat (SERT-/-) is one of the animal models used to investigate the underlying molecular mechanisms behind the genetic susceptibility to depression in humans. SERT-/- rats present decreased BDNF levels, especially BDNF exon IV, in the prefrontal cortex (PFC) and ventral hippocampus (vHIP), and display anxiety- and depression-like behavior. To investigate whether upregulating BDNF in the vHIP would meliorate the phenotype of SERT-/- rats, we overexpressed BDNF locally into the rat brain by means of stereotaxic surgery and submitted the animals to behavioral challenges, including the sucrose consumption, the open field, and forced swim tests. Additionally, we measured hypothalamus-pituitary-adrenal (HPA)-axis reactivity. The results showed that lentivirus-induced BDNF IV overexpression in the vHIP of SERT-/- rats promoted higher sucrose preference and sucrose intake, on the first day of the sucrose consumption test, indicative for decreased anhedonia-like behavior. Moreover, it decreased immobility time in the forced swim test, suggesting adaptive passive coping. Additionally, BDNF upregulation increased the time spent in the center of a novel environment, implying decreased novel-induced anxiety-like behavior. Finally, it promoted a stronger decrease in plasma corticosterone levels 60 minutes after restraint stress. In conclusion, modulation of BDNF IV levels in the vHIP of SERT-/- rats led to a positive behavioral outcome placing BDNF upregulation in the vHIP as a potential candidate for the development new therapeutic approaches targeting the improvement of depressive symptoms.

animal behavior and cognition↗

bioRxiv2020

Causal evidence of network communication in whole-brain dynamics through a multiplexed neural code

An important question in neuroscience is how local activity can be flexibly and selectively routed across the brain network. A proposed mechanism to flexibly route information is frequency division multiplexing: selective readout can be achieved by segregating the signal into non-overlapping frequency bands. Here, in wild-type mice and in a transgenic model (3xTgAD) of Alzheimers Disease (AD), we use optogenetic activation of the entorhinal cortex, concurrent whole-brain fMRI, and hidden Markov modeling. We demonstrate how inducing neuronal spiking with different theta frequencies causes spatially distinct states of brain network dynamics to emerge and to preferentially respond to one frequency, showing how selective information streams can arise from a single neuronal source of activity. This theta modulation mechanism, however, is impaired in the AD model. This work demonstrates that neuronal multiplexing is a sufficient mechanism to enable flexible brain network communication, and provides insight into the aberrant mechanisms underlying cognitive decline.

neuroscience↗