Presynaptic short-term plasticity is thought to play a major role in the process of spike transfer within local circuits. Mossy fiber synapses between the axons of dentate gyrus (DG) granule cells and CA3 pyramidal cells (Mf-CA3 synapses) display a remarkable extent of presynaptic plasticity which endows these synaptic connections with detonator properties. The pattern of action potential firing, in the form of high frequency bursts in the DG, strongly controls the amplitude of synaptic responses and information transfer to CA3. Here we have investigated the role of presynaptic facilitation at Mf-CA3 synapses in the operation of CA3 circuits in vivo and in memory encoding. Syt7, a calcium sensor necessary for presynaptic facilitation, was selectively abrogated, in DG granule cells using Syt7 conditional KO mice (DG Syt7 KO mice). In hippocampal slices, we extend previous analysis to show that short-term presynaptic facilitation is selectively suppressed at Mf-CA3 synapses in the absence of Syt7, without any impact on basal synaptic properties and long-term potentiation. Short-term plasticity was found to be crucial for spike transfer between the DG and CA3 in conditions of naturalistic patterns of presynaptic firing. At the network level, in awake head-fixed mice, the abrogation of short-term plasticity largely reduced the co-activity of CA3 pyramidal cells. Finally, whereas DG Syt7 KO mice are not impaired in behavioral tasks based on pattern separation, they show deficits in spatial memory tasks which rely on the process of pattern completion. These results shed new light on the role of the detonator properties of DG-CA3 synapses, and give important insights into how this key synaptic feature translate at the population and behavioral levels.
{"title":"Abrogation of presynaptic facilitation at hippocampal mossy fiber synapses impacts neural ensemble activity and spatial memory","authors":"Catherine Marneffe, Noelle Grosjean, Kyrian Nicolay-Kritter, Cecile Chatras, Evan Harrel, Ashley Kees, Christophe Mulle","doi":"10.1101/2024.09.10.612312","DOIUrl":"https://doi.org/10.1101/2024.09.10.612312","url":null,"abstract":"Presynaptic short-term plasticity is thought to play a major role in the process of spike transfer within local circuits. Mossy fiber synapses between the axons of dentate gyrus (DG) granule cells and CA3 pyramidal cells (Mf-CA3 synapses) display a remarkable extent of presynaptic plasticity which endows these synaptic connections with detonator properties. The pattern of action potential firing, in the form of high frequency bursts in the DG, strongly controls the amplitude of synaptic responses and information transfer to CA3. Here we have investigated the role of presynaptic facilitation at Mf-CA3 synapses in the operation of CA3 circuits in vivo and in memory encoding. Syt7, a calcium sensor necessary for presynaptic facilitation, was selectively abrogated, in DG granule cells using Syt7 conditional KO mice (DG Syt7 KO mice). In hippocampal slices, we extend previous analysis to show that short-term presynaptic facilitation is selectively suppressed at Mf-CA3 synapses in the absence of Syt7, without any impact on basal synaptic properties and long-term potentiation. Short-term plasticity was found to be crucial for spike transfer between the DG and CA3 in conditions of naturalistic patterns of presynaptic firing. At the network level, in awake head-fixed mice, the abrogation of short-term plasticity largely reduced the co-activity of CA3 pyramidal cells. Finally, whereas DG Syt7 KO mice are not impaired in behavioral tasks based on pattern separation, they show deficits in spatial memory tasks which rely on the process of pattern completion. These results shed new light on the role of the detonator properties of DG-CA3 synapses, and give important insights into how this key synaptic feature translate at the population and behavioral levels.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
High-level cognitive skill development relies on genetic and environmental factors, tied to brain structure and function. Inter-individual variability in language and music skills has been repeatedly associated with the structure of the auditory cortex: the shape, size and asymmetry of the transverse temporal gyrus (TTG) or gyri (TTGs). TTG is highly variable in shape and size, some individuals having one single gyrus (also referred to as Heschl's gyrus, HG) while others presenting duplications (with a common stem or fully separated) or higher-order multiplications of TTG. Both genetic and environmental influences on children's cognition, behavior, and brain can to some to degree be traced back to familial and parental factors. In the current study, using a unique MRI dataset of parents and children (135 individuals from 37 families), we ask whether the anatomy of the auditory cortex is related to reading skills, and whether there are intergenerational effects on TTG(s) anatomy. For this, we performed detailed, automatic segmentations of HG and of additional TTG(s), when present, extracting volume, surface area, thickness and shape of the gyri. We tested for relationships between these and reading skill, and assessed their degree of familial similarity and intergenerational transmission effects. We found that volume and area of all identified left TTG(s) combined was positively related to reading scores, both in children and adults. With respect to intergenerational similarities in the structure of the auditory cortex, we identified structural brain similarities for parent-child pairs of the 1st TTG (Heschl's gyrus, HG) (in terms of volume, area and thickness for the right HG, and shape for the left HG) and of the lateralization of all TTG(s) surface area for father-child pairs. Both the HG and TTG-lateralization findings were significantly more likely for parent-child dyads than for unrelated adult-child pairs. Furthermore, we established characteristics of parents' TTG that are related to better reading abilities in children: fathers' small left HG, and a small ratio of HG to planum temporale. Our results suggest intergenerational transmission of specific structural features of the auditory cortex; these may arise from genetics and/or from shared environment.
{"title":"Intergenerational transmission of the structure of the auditory cortex and reading skills","authors":"Olga Kepinska, Florence Bouhali, Giulio Degano, Raphael Berthele, Hiroko Tanaka, Fumiko Hoeft, Narly Golestani","doi":"10.1101/2024.09.11.610780","DOIUrl":"https://doi.org/10.1101/2024.09.11.610780","url":null,"abstract":"High-level cognitive skill development relies on genetic and environmental factors, tied to brain structure and function. Inter-individual variability in language and music skills has been repeatedly associated with the structure of the auditory cortex: the shape, size and asymmetry of the transverse temporal gyrus (TTG) or gyri (TTGs). TTG is highly variable in shape and size, some individuals having one single gyrus (also referred to as Heschl's gyrus, HG) while others presenting duplications (with a common stem or fully separated) or higher-order multiplications of TTG. Both genetic and environmental influences on children's cognition, behavior, and brain can to some to degree be traced back to familial and parental factors. In the current study, using a unique MRI dataset of parents and children (135 individuals from 37 families), we ask whether the anatomy of the auditory cortex is related to reading skills, and whether there are intergenerational effects on TTG(s) anatomy. For this, we performed detailed, automatic segmentations of HG and of additional TTG(s), when present, extracting volume, surface area, thickness and shape of the gyri. We tested for relationships between these and reading skill, and assessed their degree of familial similarity and intergenerational transmission effects. We found that volume and area of all identified left TTG(s) combined was positively related to reading scores, both in children and adults. With respect to intergenerational similarities in the structure of the auditory cortex, we identified structural brain similarities for parent-child pairs of the 1st TTG (Heschl's gyrus, HG) (in terms of volume, area and thickness for the right HG, and shape for the left HG) and of the lateralization of all TTG(s) surface area for father-child pairs. Both the HG and TTG-lateralization findings were significantly more likely for parent-child dyads than for unrelated adult-child pairs. Furthermore, we established characteristics of parents' TTG that are related to better reading abilities in children: fathers' small left HG, and a small ratio of HG to planum temporale. Our results suggest intergenerational transmission of specific structural features of the auditory cortex; these may arise from genetics and/or from shared environment.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1101/2024.09.11.612456
Ashley E Marquardt, Mahashweta Basu, Jonathan W VanRyzin, Seth A Ament, Margaret M McCarthy
Social play is a dynamic behavior known to be sexually differentiated; in most species, males play more than females, a sex difference driven in large part by the medial amygdala (MeA). Despite the well-conserved nature of this sex difference and the importance of social play for appropriate maturation of brain and behavior, the full mechanism establishing the sex bias in play is unknown. Here, we explore the transcriptome of playfulness in the juvenile rat MeA, assessing differences in gene expression between high- and low-playing animals of both sexes via bulk RNA-sequencing. Using weighted gene co-expression network analysis (WGCNA) to identify gene modules combined with analysis of differentially expressed genes (DEGs), we demonstrate that the transcriptomic profile in the juvenile rat MeA associated with playfulness is largely distinct in males compared to females. Of the 13 play-associated WGCNA networks identified, only two were associated with play in both sexes, and very few DEGs associated with playfulness were shared between males and females. Data from our parallel single-cell RNA-sequencing experiments using amygdala samples from newborn male and female rats suggests that inhibitory neurons drive this sex difference, as the majority of sex-biased DEGs in the neonatal amygdala are enriched within this population. Supporting this notion, we demonstrate that inhibitory neurons comprise the majority of play-active cells in the juvenile MeA, with males having a greater number of play-active cells than females, of which a larger proportion are GABAergic. Through integrative bioinformatic analyses, we further explore the expression, function, and cell-type specificity of key play-associated modules and the regulator hub genes predicted to drive them, providing valuable insight into the sex-biased mechanisms underlying this fundamental social behavior.
{"title":"The transcriptome of playfulness is sex-biased in the juvenile rat medial amygdala: a role for inhibitory neurons","authors":"Ashley E Marquardt, Mahashweta Basu, Jonathan W VanRyzin, Seth A Ament, Margaret M McCarthy","doi":"10.1101/2024.09.11.612456","DOIUrl":"https://doi.org/10.1101/2024.09.11.612456","url":null,"abstract":"Social play is a dynamic behavior known to be sexually differentiated; in most species, males play more than females, a sex difference driven in large part by the medial amygdala (MeA). Despite the well-conserved nature of this sex difference and the importance of social play for appropriate maturation of brain and behavior, the full mechanism establishing the sex bias in play is unknown. Here, we explore the transcriptome of playfulness in the juvenile rat MeA, assessing differences in gene expression between high- and low-playing animals of both sexes via bulk RNA-sequencing. Using weighted gene co-expression network analysis (WGCNA) to identify gene modules combined with analysis of differentially expressed genes (DEGs), we demonstrate that the transcriptomic profile in the juvenile rat MeA associated with playfulness is largely distinct in males compared to females. Of the 13 play-associated WGCNA networks identified, only two were associated with play in both sexes, and very few DEGs associated with playfulness were shared between males and females. Data from our parallel single-cell RNA-sequencing experiments using amygdala samples from newborn male and female rats suggests that inhibitory neurons drive this sex difference, as the majority of sex-biased DEGs in the neonatal amygdala are enriched within this population. Supporting this notion, we demonstrate that inhibitory neurons comprise the majority of play-active cells in the juvenile MeA, with males having a greater number of play-active cells than females, of which a larger proportion are GABAergic. Through integrative bioinformatic analyses, we further explore the expression, function, and cell-type specificity of key play-associated modules and the regulator hub genes predicted to drive them, providing valuable insight into the sex-biased mechanisms underlying this fundamental social behavior.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142187116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.12.607537
Christoph Kayser, Herbert Heuer
Combining multisensory cues is fundamental for perception and action, and reflected by two frequently-studied phenomena: multisensory integration and sensory recalibration. In the context of audio-visual spatial signals, these are exemplified by the ventriloquism effect and its aftereffect. The ventriloquism effect occurs when the perceived location of a sound is biased by a concurrent visual stimulus, while the aftereffect manifests as a recalibration of sound localization after exposure to spatially discrepant stimuli. The relationship between these processes - whether recalibration is a direct consequence of integration or operates independently - remains debated. This study investigates the role of causal inference in these processes by examining whether trial-wise judgments of audio-visual stimuli as originating from a common cause influence both the ventriloquism effect and the immediate aftereffect. Using a spatial paradigm, participants made explicit judgments about the common cause of stimulus pairs, and their influence on both perceptual biases was assessed. Our results indicate that while multisensory integration is contingent on common cause judgments, the immediate recalibration effect is not. This suggests that recalibration can occur independently of the perceived commonality of the multisensory stimuli, challenging the notion that recalibration is solely a byproduct of integration.
{"title":"Perceived multisensory common cause relations shape the ventriloquism effect but only marginally the trial-wise aftereffect","authors":"Christoph Kayser, Herbert Heuer","doi":"10.1101/2024.08.12.607537","DOIUrl":"https://doi.org/10.1101/2024.08.12.607537","url":null,"abstract":"Combining multisensory cues is fundamental for perception and action, and reflected by two frequently-studied phenomena: multisensory integration and sensory recalibration. In the context of audio-visual spatial signals, these are exemplified by the ventriloquism effect and its aftereffect. The ventriloquism effect occurs when the perceived location of a sound is biased by a concurrent visual stimulus, while the aftereffect manifests as a recalibration of sound localization after exposure to spatially discrepant stimuli. The relationship between these processes - whether recalibration is a direct consequence of integration or operates independently - remains debated. This study investigates the role of causal inference in these processes by examining whether trial-wise judgments of audio-visual stimuli as originating from a common cause influence both the ventriloquism effect and the immediate aftereffect. Using a spatial paradigm, participants made explicit judgments about the common cause of stimulus pairs, and their influence on both perceptual biases was assessed. Our results indicate that while multisensory integration is contingent on common cause judgments, the immediate recalibration effect is not. This suggests that recalibration can occur independently of the perceived commonality of the multisensory stimuli, challenging the notion that recalibration is solely a byproduct of integration.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141947300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.11.607484
Zhaoze Wang, Ronald W Di Tullio, Spencer Rooke, Vijay Balasubramanian
The vertebrate hippocampus is believed to use recurrent connectivity in area CA3 to support episodic memory recall from partial cues. This brain area also contains place cells, whose location-selective firing fields implement maps supporting spatial memory. Here we show that place cells emerge in networks trained to remember temporally continuous sensory episodes. We model CA3 as a recurrent autoencoder that recalls and reconstructs sensory experiences from noisy and partially occluded observations by agents traversing simulated arenas. The agents move in realistic trajectories modeled from rodents and environments are modeled as continuously varying, high-dimensional, sensory experience maps (spatially smoothed Gaussian random fields). Training our autoencoder to accurately pattern-complete and reconstruct sensory experiences with a constraint on total activity causes spatially localized firing fields, i.e., place cells, to emerge in the encoding layer. The emergent place fields reproduce key aspects of hippocampal phenomenology: a) remapping (maintenance of and reversion to distinct learned maps in different environments), implemented via repositioning of experience manifolds in the network's hidden layer, b) orthogonality of spatial representations in different arenas, c) robust place field emergence in differently shaped rooms, with single units showing multiple place fields in large or complex spaces, and d) slow representational drift of place fields. We argue that these results arise because continuous traversal of space makes sensory experience temporally continuous. We make testable predictions: a) rapidly changing sensory context will disrupt place fields, b) place fields will form even if recurrent connections are blocked, but reversion to previously learned representations upon remapping will be abolished, c) the dimension of temporally smooth experience sets the dimensionality of place fields, including during virtual navigation of abstract spaces.
{"title":"Time Makes Space: Emergence of Place Fields in Networks Encoding Temporally Continuous Sensory Experiences","authors":"Zhaoze Wang, Ronald W Di Tullio, Spencer Rooke, Vijay Balasubramanian","doi":"10.1101/2024.08.11.607484","DOIUrl":"https://doi.org/10.1101/2024.08.11.607484","url":null,"abstract":"The vertebrate hippocampus is believed to use recurrent connectivity in area CA3 to support episodic memory recall from partial cues. This brain area also contains place cells, whose location-selective firing fields implement maps supporting spatial memory. Here we show that place cells emerge in networks trained to remember temporally continuous sensory episodes. We model CA3 as a recurrent autoencoder that recalls and reconstructs sensory experiences from noisy and partially occluded observations by agents traversing simulated arenas. The agents move in realistic trajectories modeled from rodents and environments are modeled as continuously varying, high-dimensional, sensory experience maps (spatially smoothed Gaussian random fields). Training our autoencoder to accurately pattern-complete and reconstruct sensory experiences with a constraint on total activity causes spatially localized firing fields, i.e., place cells, to emerge in the encoding layer. The emergent place fields reproduce key aspects of hippocampal phenomenology: a) remapping (maintenance of and reversion to distinct learned maps in different environments), implemented via repositioning of experience manifolds in the network's hidden layer, b) orthogonality of spatial representations in different arenas, c) robust place field emergence in differently shaped rooms, with single units showing multiple place fields in large or complex spaces, and d) slow representational drift of place fields. We argue that these results arise because continuous traversal of space makes sensory experience temporally continuous. We make testable predictions: a) rapidly changing sensory context will disrupt place fields, b) place fields will form even if recurrent connections are blocked, but reversion to previously learned representations upon remapping will be abolished, c) the dimension of temporally smooth experience sets the dimensionality of place fields, including during virtual navigation of abstract spaces.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141947299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.12.607184
Charles K Dowell, Thomas Hawkins, Isaac H Bianco
Animals construct diverse behavioural repertoires by moving a limited number of body parts with varied kinematics and patterns of coordination. There is evidence that distinct movements can be generated by changes in activity dynamics within a common pool of motoneurons, or by selectively engaging specific subsets of motoneurons in a task-dependent manner. However, in most cases we have an incomplete understanding of the patterns of motoneuron activity that generate distinct actions and how upstream premotor circuits select and assemble such motor programmes. In this study, we used two closely related but kinematically distinct types of saccadic eye movement in larval zebrafish as a model to examine circuit control of movement diversity. In contrast to the prevailing view of a final common pathway, we found that in oculomotor nucleus, distinct subsets of motoneurons were engaged for each saccade type. This type-specific recruitment was topographically organised and aligned with ultrastructural differences in motoneuron morphology and afferent synaptic innervation. Medially located motoneurons were active for both saccade types and circuit tracing revealed a type-agnostic premotor pathway that appears to control their recruitment. By contrast, a laterally located subset of motoneurons was specifically active for hunting-associated saccades and received premotor input from pretectal hunting command neurons. Our data support a model in which generalist and action-specific premotor pathways engage distinct subsets of motoneurons to elicit varied movements of the same body part that subserve distinct behavioural functions.
{"title":"Subsets of extraocular motoneurons produce kinematically distinct saccades during hunting and exploration.","authors":"Charles K Dowell, Thomas Hawkins, Isaac H Bianco","doi":"10.1101/2024.08.12.607184","DOIUrl":"https://doi.org/10.1101/2024.08.12.607184","url":null,"abstract":"Animals construct diverse behavioural repertoires by moving a limited number of body parts with varied kinematics and patterns of coordination. There is evidence that distinct movements can be generated by changes in activity dynamics within a common pool of motoneurons, or by selectively engaging specific subsets of motoneurons in a task-dependent manner. However, in most cases we have an incomplete understanding of the patterns of motoneuron activity that generate distinct actions and how upstream premotor circuits select and assemble such motor programmes. In this study, we used two closely related but kinematically distinct types of saccadic eye movement in larval zebrafish as a model to examine circuit control of movement diversity. In contrast to the prevailing view of a final common pathway, we found that in oculomotor nucleus, distinct subsets of motoneurons were engaged for each saccade type. This type-specific recruitment was topographically organised and aligned with ultrastructural differences in motoneuron morphology and afferent synaptic innervation. Medially located motoneurons were active for both saccade types and circuit tracing revealed a type-agnostic premotor pathway that appears to control their recruitment. By contrast, a laterally located subset of motoneurons was specifically active for hunting-associated saccades and received premotor input from pretectal hunting command neurons. Our data support a model in which generalist and action-specific premotor pathways engage distinct subsets of motoneurons to elicit varied movements of the same body part that subserve distinct behavioural functions.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141947298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.11.607040
Zeyuan Ye, Ralf Wessel, Tom P. Franken
To make sense of visual scenes, the brain must segment foreground from background. This is thought to be facilitated by neurons in the primate visual system that encode border ownership (BOS), i.e. whether a local border is part of an object on one or the other side of the border. It is unclear how these signals emerge in neural networks without a teaching signal of what is foreground and background. In this study, we investigated whether BOS signals exist in PredNet, a self-supervised artificial neural network trained to predict the next image frame of natural video sequences. We found that a significant number of units in PredNet are selective for BOS. Moreover these units share several other properties with the BOS neurons in the brain, including robustness to scene variations that constitute common object transformations in natural videos, and hysteresis of BOS signals. Finally, we performed ablation experiments and found that BOS units contribute more to prediction than non-BOS units for videos with moving objects. Our findings indicate that BOS units are especially useful to predict future input in natural videos, even when networks are not required to segment foreground from background. This suggests that BOS neurons in the brain might be the result of evolutionary or developmental pressure to predict future input in natural, complex dynamic visual environments.
{"title":"Brain-like border ownership signals support prediction of natural videos","authors":"Zeyuan Ye, Ralf Wessel, Tom P. Franken","doi":"10.1101/2024.08.11.607040","DOIUrl":"https://doi.org/10.1101/2024.08.11.607040","url":null,"abstract":"To make sense of visual scenes, the brain must segment foreground from background. This is thought to be facilitated by neurons in the primate visual system that encode border ownership (BOS), i.e. whether a local border is part of an object on one or the other side of the border. It is unclear how these signals emerge in neural networks without a teaching signal of what is foreground and background. In this study, we investigated whether BOS signals exist in PredNet, a self-supervised artificial neural network trained to predict the next image frame of natural video sequences. We found that a significant number of units in PredNet are selective for BOS. Moreover these units share several other properties with the BOS neurons in the brain, including robustness to scene variations that constitute common object transformations in natural videos, and hysteresis of BOS signals. Finally, we performed ablation experiments and found that BOS units contribute more to prediction than non-BOS units for videos with moving objects. Our findings indicate that BOS units are especially useful to predict future input in natural videos, even when networks are not required to segment foreground from background. This suggests that BOS neurons in the brain might be the result of evolutionary or developmental pressure to predict future input in natural, complex dynamic visual environments.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141969861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.11.607526
Hyunyoung Kim, Sanghee Shin, Jong-Seo Kim, Hyungju Park
The exercise induced enhancement of learning and memory is thought to be regulated by interactions between body and brain via secretory proteins in the blood plasma. Given the prominent role that skeletal muscle plays during exercise, the beneficial effects of exercise on cognitive functions appear to be mediated by muscle derived secretory factors including myokines. However, the specific myokines that exert beneficial effects on cognitive functions remain to be elucidated. Here, we reveal that a novel myokine, Serpina1e, acts a molecular mediator that directly supports long term memory formation in the hippocampus. Using an in vivo myokine labeling mouse model, proteomic analysis revealed that the Serpina1 family of proteins are the myokines whose levels increased the most in plasma after chronic aerobic exercise for 4 weeks. Systemic delivery of recombinant Serpina1e into sedentary mice was sufficient for reproducing the beneficial effect of exercise on hippocampus associated cognitive functions. Moreover, plasma Serpina1e can cross the blood cerebral spinal fluid (CSF) barrier and blood brain barrier to reach the brain, thereby influencing hippocampal function. Indeed, an increase in the plasma level of Serpina1e promoted hippocampal neurogenesis, increased the levels of brain-derived neurotrophic factor (BDNF) and induced neurite growth. Our findings reveal that Serpina1e is a myokine that migrates to the brain and mediates exercise induced memory enhancement by triggering neurotrophic growth signaling in the hippocampus. This discovery elucidates the molecular mechanisms underlying the beneficial effects of exercise on cognitive function and may have implications for the development of novel therapeutic interventions for alleviating cognitive disorders.
{"title":"Serpina1e mediates the exercise-induced enhancement of hippocampal memory","authors":"Hyunyoung Kim, Sanghee Shin, Jong-Seo Kim, Hyungju Park","doi":"10.1101/2024.08.11.607526","DOIUrl":"https://doi.org/10.1101/2024.08.11.607526","url":null,"abstract":"The exercise induced enhancement of learning and memory is thought to be regulated by interactions between body and brain via secretory proteins in the blood plasma. Given the prominent role that skeletal muscle plays during exercise, the beneficial effects of exercise on cognitive functions appear to be mediated by muscle derived secretory factors including myokines. However, the specific myokines that exert beneficial effects on cognitive functions remain to be elucidated. Here, we reveal that a novel myokine, Serpina1e, acts a molecular mediator that directly supports long term memory formation in the hippocampus. Using an in vivo myokine labeling mouse model, proteomic analysis revealed that the Serpina1 family of proteins are the myokines whose levels increased the most in plasma after chronic aerobic exercise for 4 weeks. Systemic delivery of recombinant Serpina1e into sedentary mice was sufficient for reproducing the beneficial effect of exercise on hippocampus associated cognitive functions. Moreover, plasma Serpina1e can cross the blood cerebral spinal fluid (CSF) barrier and blood brain barrier to reach the brain, thereby influencing hippocampal function. Indeed, an increase in the plasma level of Serpina1e promoted hippocampal neurogenesis, increased the levels of brain-derived neurotrophic factor (BDNF) and induced neurite growth. Our findings reveal that Serpina1e is a myokine that migrates to the brain and mediates exercise induced memory enhancement by triggering neurotrophic growth signaling in the hippocampus. This discovery elucidates the molecular mechanisms underlying the beneficial effects of exercise on cognitive function and may have implications for the development of novel therapeutic interventions for alleviating cognitive disorders.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141947302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.11.607503
Ravinderjit Singh, Hari Bharadwaj
Human studies of auditory temporal processing and the effects therein of aging, hearing loss, musicianship, and other auditory processing disorders have conventionally employed brainstem evoked potentials (e.g., FFRs/EFRs targeting specific modulation frequencies). Studies of temporal processing in forebrain structures are fewer and are often restricted to the 40 Hz steady-state response. One factor contributing to the limited investigation is the lack of a fast and reliable method to characterize temporal processing non-invasively in humans over a wide range of modulation frequencies. Here, we use a system-identification approach where white noise, modulated using an extended maximum-length sequence (em-seq), is employed to target stimulus energy toward a modulation-frequency range of interest and efficiently obtain a robust auditory modulation-temporal response function or `mod-TRF'. The mod-TRF can capture activity from sources in the early processing pathway (5-7 ms latency), middle-latency region (MLR), and late latency region (LLR). The mod-TRF is a high-resolution, modular assay of the temporal modulation transfer function (tMTF) in that the distinct neural components contributing to the tMTF can be separated on the basis of their latency, modulation frequency band, and scalp topography. This decomposition provides the insight that the seemingly random individual variation in the shape of the tMTF can be understood as arising from individual differences in the weighting and latency of similar underlying neural sources in the composite scalp response. We measured the mod-TRF under different states of attention and found a reduction in latency or enhancement of amplitude of the response from specific sources. Surprisingly, we found that attention effects can extend to the earliest parts of the processing pathway (~5ms) in highly demanding tasks. Taken together, the mod-TRF is a promising tool for dissecting auditory temporal processing and obtain further insight into a variety of phenomenon such as aging, hearing loss, and neural pathology.
{"title":"Efficient modular system identification provides a high-resolution assay of temporal processing and reveals the multilevel effects of attention along the human auditory pathway","authors":"Ravinderjit Singh, Hari Bharadwaj","doi":"10.1101/2024.08.11.607503","DOIUrl":"https://doi.org/10.1101/2024.08.11.607503","url":null,"abstract":"Human studies of auditory temporal processing and the effects therein of aging, hearing loss, musicianship, and other auditory processing disorders have conventionally employed brainstem evoked potentials (e.g., FFRs/EFRs targeting specific modulation frequencies). Studies of temporal processing in forebrain structures are fewer and are often restricted to the 40 Hz steady-state response. One factor contributing to the limited investigation is the lack of a fast and reliable method to characterize temporal processing non-invasively in humans over a wide range of modulation frequencies. Here, we use a system-identification approach where white noise, modulated using an extended maximum-length sequence (em-seq), is employed to target stimulus energy toward a modulation-frequency range of interest and efficiently obtain a robust auditory modulation-temporal response function or `mod-TRF'. The mod-TRF can capture activity from sources in the early processing pathway (5-7 ms latency), middle-latency region (MLR), and late latency region (LLR). The mod-TRF is a high-resolution, modular assay of the temporal modulation transfer function (tMTF) in that the distinct neural components contributing to the tMTF can be separated on the basis of their latency, modulation frequency band, and scalp topography. This decomposition provides the insight that the seemingly random individual variation in the shape of the tMTF can be understood as arising from individual differences in the weighting and latency of similar underlying neural sources in the composite scalp response. We measured the mod-TRF under different states of attention and found a reduction in latency or enhancement of amplitude of the response from specific sources. Surprisingly, we found that attention effects can extend to the earliest parts of the processing pathway (~5ms) in highly demanding tasks. Taken together, the mod-TRF is a promising tool for dissecting auditory temporal processing and obtain further insight into a variety of phenomenon such as aging, hearing loss, and neural pathology.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141969860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Animals adapt to environmental challenges with long-term changes at the behavioral, circuit, cellular, and synaptic levels which often require new protein synthesis. The discovery of reversible N6-methyladenosine (m6A) modifications of mRNA has revealed an important layer of post-transcriptional regulation which affects almost every phase of mRNA metabolism and therefore translational control. Many in vitro and in vivo studies have demonstrated the significant role of m6A in cell differentiation and survival, but its role in adult neurons is understudied. We used cell-type specific gene deletion of Mettl14, which encodes one of the subunits of the m6A methyltransferase, and Ythdf1, which encodes one of the cytoplasmic m6A reader proteins, in dopamine D1 receptor expressing or D2 receptor expressing neurons. Mettl14 or Ythdf1 deficiency blunted responses to environmental challenges at the behavioral, cellular, and molecular levels. In three different behavioral paradigms, gene deletion of either Mettl14 or Ythdf1 in D1 neurons impaired D1-dependent learning, whereas gene deletion of either Mettl14 or Ythdf1 in D2 neurons impaired D2-dependent learning. At the cellular level, modulation of D1 and D2 neuron firing in response to changes in environments was blunted in all three behavioral paradigms in mutant mice. Ythdf1 deletion resembled impairment caused by Mettl14 deletion in a cell type-specific manner, suggesting YTHDF1 is the main mediator of the functional consequences of m6A mRNA methylation in the striatum. At the molecular level, while striatal neurons in control mice responded to elevated cAMP by increasing de novo protein synthesis, striatal neurons in Ythdf1 knockout mice didn't. Finally, boosting dopamine release by cocaine drastically increased YTHDF1 binding to many mRNA targets in the striatum, especially those that encode structural proteins, suggesting the initiation of long-term neuronal and/or synaptic structural changes. While the m6A-YTHDF1 pathway has similar functional significance at cellular level, its cell type specific deficiency in D1 and D2 neurons often resulted in contrasting behavioral phenotypes, allowing us to cleanly dissociate the opposing yet cooperative roles of D1 and D2 neurons.
{"title":"YTHDF1 mediates translational control by m6A mRNA methylation in adaptation to environmental challenges","authors":"Zhuoyue Shi, Kailong Wen, Zhongyu Zou, Wenqin Fu, Kathryn Guo, Nabilah H Sammudin, Xiangbin Ruan, Shivang Sullere, Shuai Wang, Xiaochang Zhang, Gopal Thinakaran, Chuan He, Xiaoxi Zhuang","doi":"10.1101/2024.08.07.607063","DOIUrl":"https://doi.org/10.1101/2024.08.07.607063","url":null,"abstract":"Animals adapt to environmental challenges with long-term changes at the behavioral, circuit, cellular, and synaptic levels which often require new protein synthesis. The discovery of reversible N6-methyladenosine (m<sup>6</sup>A) modifications of mRNA has revealed an important layer of post-transcriptional regulation which affects almost every phase of mRNA metabolism and therefore translational control. Many in vitro and in vivo studies have demonstrated the significant role of m<sup>6</sup>A in cell differentiation and survival, but its role in adult neurons is understudied. We used cell-type specific gene deletion of <em>Mettl14</em>, which encodes one of the subunits of the m<sup>6</sup>A methyltransferase, and <em>Ythdf1</em>, which encodes one of the cytoplasmic m<sup>6</sup>A reader proteins, in dopamine D1 receptor expressing or D2 receptor expressing neurons. <em>Mettl14</em> or <em>Ythdf1</em> deficiency blunted responses to environmental challenges at the behavioral, cellular, and molecular levels. In three different behavioral paradigms, gene deletion of either <em>Mettl14</em> or <em>Ythdf1</em> in D1 neurons impaired D1-dependent learning, whereas gene deletion of either <em>Mettl14</em> or <em>Ythdf1</em> in D2 neurons impaired D2-dependent learning. At the cellular level, modulation of D1 and D2 neuron firing in response to changes in environments was blunted in all three behavioral paradigms in mutant mice. <em>Ythdf1</em> deletion resembled impairment caused by <em>Mettl14</em> deletion in a cell type-specific manner, suggesting YTHDF1 is the main mediator of the functional consequences of m<sup>6</sup>A mRNA methylation in the striatum. At the molecular level, while striatal neurons in control mice responded to elevated cAMP by increasing <em>de novo</em> protein synthesis, striatal neurons in <em>Ythdf1</em> knockout mice didn't. Finally, boosting dopamine release by cocaine drastically increased YTHDF1 binding to many mRNA targets in the striatum, especially those that encode structural proteins, suggesting the initiation of long-term neuronal and/or synaptic structural changes. While the m<sup>6</sup>A-YTHDF1 pathway has similar functional significance at cellular level, its cell type specific deficiency in D1 and D2 neurons often resulted in contrasting behavioral phenotypes, allowing us to cleanly dissociate the opposing yet cooperative roles of D1 and D2 neurons.","PeriodicalId":501581,"journal":{"name":"bioRxiv - Neuroscience","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141947301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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