Biology subjects

Kumar, A.

Publications and source records attributed to Kumar, A..

At least 163 records · Page 9Linked to original sources

bioRxiv2025

Implication of novel variants of BMP2 in isolated congenital heart disease: Functional characterization by in silico and invitro approaches

Bone morphogenic protein2 (BMP2), a member of TGF-{beta} super-family, known to play a wide range of roles during embryonic development, particularly in the formation of bone/skeleton, differentiation of neurons, skeletal muscle, and development of cardiac valve septa and outflow tract. BMP2 haploinsufficiency is reported to cause multiple congenital malformations including cardiac defects mainly endocardial cushion formation and chamber specification. To investigate the functional relevance of BMP2 variations in isolated CHD cases, we performed genetic screening of BMP2 in 285 CHD probands along with 400 healthy controls by Sangers method. Five non-synonymous variants namely, an already known variant p.Ser37Ala in N-terminal region, one nonsense variant, p.Lys241X in pro-peptide region and three missense variants p.His321Leu, p.Glu328Lys and p.Ser351Cys in mature domain, were identified in 8 unrelated CHD cases. In vitro functional analysis by western blotting depicted an increase in phosphorylation of SMAD1/5 due to all five variants. Furthermore, overexpression of cardiac-specific downstream target genes namely Smad1, Smad4, Smad5, Nkx2.5, Gata4 and Irx4 of the BMP pathway was observed in response to all the variants. Luciferase assay also validated the enhanced expression of multiple downstream promoters Id1-luc, Id3-luc, Tlx2-luc, and p(SBE)4-luc. Additionally, computational analysis of RNA structural features and protein secondary and tertiary structural changes also highlighted the increased activity of mutants, possibly due to enhanced interactions of mutant proteins with their binding partners owing to more stable structures. Overall, this is the first study which characterized the functional association of BMP2 variants with the pathogenesis of CHD by in vitro and in silico methods.

genetics↗

bioRxiv2025

Epigenetic inheritance of complex learning abilities in the mammalian brain

For several decades, the question of whether cognitive and learning capacities can be inherited through non-genetic mechanisms has been the subject of ongoing debate. Here, we provide the first evidence of transgenerational inheritance of enhanced ability to learn complex tasks in the mammalian rodent brain. These inherited learning enhancements are not limited to specific stimuli, sensory modalities, or learning paradigms. Using behavioral, cellular biophysical, methylomics, genetics and molecular methods, we find that the inherited epigenetic modifications reflect an enhanced neuronal learning state, driven by increased intrinsic neuronal excitability in most pyramidal neurons in the relevant neuronal networks. This enhancement is mediated by persistent downregulation of the muscarinic M-current and is associated with widespread changes in DNA methylation, notably within coding genes associated with the M-current, the Kv7 pathway, in the hippocampi of trained F0 rats, as well as in non-coding RNAs in their sperm samples. Remarkably, a significant portion of these DNA methylation changes were also observed in the hippocampi of their untrained F1 offspring. These findings suggest that complex learning abilities can be inherited in the mammalian brain, as the offspring of trained rodents are born with the biophysical modifications that enable them to become super-learners, the exact change that occurs in their parents brains only after the rule learning.

neuroscience↗

bioRxiv2025

Replicating the Gold Standard: A Novel Female Chronic Social Defeat Stress Model (femCSDS) for Studying Sex Differences in Depression

Depression shows significant sex differences in prevalence and neurobiological underpinnings, yet preclinical research investigating the pathophysiology of depression and the efficacy of antidepressants has predominantly relied on male models. Here, we establish a novel female chronic social defeat stress paradigm by leveraging the natural aggression of parous CD1 females, co-housed with castrated males to induce aggression while eliminating confounding sexual behaviors and without hormonal or surgical manipulations. Selected aggressive females reliably displayed offensive behaviors toward C57BL/6NCrl intruders across repeated encounters. Defeated female mice exhibited pronounced depression-like behaviors, including social withdrawal, anhedonia, behavioral despair, and elevated anxiety-like responses. Biochemical analysis revealed elevated glutamate levels in Nucleus Accumbens (NAc) and caudate putamen (CPu). Alterations in EAAT1, GRIN2B, and Neurabin expression were observed in CPu, indicating excitotoxic stress and compromised synaptic integrity. Label free Quantitative MS-MS analysis of NAc revealed 1194 significantly dysregulated proteins. Ingenuity Pathway Analysis highlighted canonical pathway disruptions in synaptogenesis signaling pathway and glutamate signaling pathway. Disease and function analysis revealed enrichment in neuroinflammation, synaptic dysfunction, and mitochondrial dysfunction. Given the extensive literature on male CSDS and its established pathophysiology, we aimed and successfully developed female-specific replica model of traditional male CSDS, enabling direct comparison and elucidation of sex differences in depression pathophysiology.

neuroscience↗

bioRxiv2025

Genome-wide analysis of social behaviour in context: a meta-regression approach across social domains, reporters and developmental stages

Social behaviour is a heritable, context-dependent trait that changes across social settings and development, influencing wellbeing and mental health. We present the first genome-wide meta-regression study of social behaviour from infancy to early adulthood, leveraging 491,246 repeat measures of low prosocial behaviour and peer/social difficulties in European-ancestry cohorts (Neff=121,777, Nind=73,321). We modelled heterogeneity in genetic effects across social domains, informants, and ages (2-29 years), capturing social context through genomic influences. Six loci were identified, including variation within CADM2 (p=2.51x10-9). The SNP-based heritability was modest (2-7%), and the genetic architecture of social behaviour multidimensional. Polygenic scores demonstrated predictability and accuracy in independent European-ancestry cohorts and, partially, in African-ancestry cohorts (Nind=16,305). Genetic correlations with later-life and mental health outcomes showed context-dependent patterns. Modelling predicted onsets of associations with social behaviour revealed distinct profiles, as observed for autism, ADHD, depression and schizophrenia, highlighting novel opportunities to genetically proxy developmental trajectories.

genomics↗

bioRxiv2025

PRESTIGE-ST: Patch Resolution and Encoder STrategies for Inference of Gene Expression from Spatial Transcriptomics

Spatial Transcriptomics (ST) integrates histology with spatially resolved gene expression, offering rich insights into tissue architecture and function. However, its clinical and large-scale deployment is hindered by high costs, technical complexity, and limited accessibility. To address this, computational pathology methods have emerged to predict gene expression directly from histology images, typically framing the task as a multi-output regression problem mapping image patches to gene expression profiles. While several Convolutional Neural Network (CNN) models have been proposed, little is known about how performance is influenced by (a) the number of trainable parameters and (b) the patch size used for prediction. Moreover, existing studies rely primarily on quantitative metrics and overlook biological relevance of predictions. In this study, we systematically evaluated multiple convolution based models (including a Vision Transformer (ViT) model) with different patch sizes on the Xenium based Autoimmune Machine Learning Challenge (AMLC) dataset. We assessed model performance on both globally expressed genes and subsets enriched for immune or disease associated pathways. Our findings reveal that compact CNNs trained on larger patches outperform deeper models, offering superior accuracy in predicting gene expression, especially for biologically important genes. These insights provide practical guidance for designing efficient and biologically meaningful models in the emerging field of image-based gene expression prediction. CCS CONCEPTSComputing methodologies [->] Computer vision; Neural networks; * Applied computing [->] Computational genomics; Imaging.

pathology↗

bioRxiv2025

BIOPHYSICAL MECHANISMS UNDERLYING THE GENERATION AND MAINTENANCE OF RULE-LEARNING ENGRAM

Training rodents in a particularly difficult olfactory-discrimination task results with acquisition of high skill to perform the task superbly, termed rule-learning. We show that rule-learning occurs abruptly, in a "light bulb moment". Using whole-cell patch-clamp recordings in the piriform cortex of Fos2A-iCreER/TRAP2 mice, we targeted activated neurons, expressing immediate early genes (IEG). From the onset of training, IEG-positive neurons from trained animals display enhanced intrinsic excitability. Subsequently, synaptic excitation and inhibition is enhanced in these neurons, in a coordinated, cell-wide process. In parallel, the density of IEG-expressing neurons sharply declines. Double labeling with TRAP and c-Fos reveals that nearly two-thirds of the rule-memory engram neurons were engaged from the beginning of training. Silencing TRAP-expressing neurons using DREADDs leads to a complete loss of rule memory. We propose that rule learning occurs at a discrete moment, and is developed through a gradual process that stabilizes the memory of the rule.

neuroscience↗

bioRxiv2025

Mesocorticolimbic reinforcement learning of reward representation and value provides an integrated mechanistic account for schizophrenia

Mesocorticolimbic dopamine projections are crucial for value learning, motivational control, and cognitive functions, but their precise neurocomputational roles remain elusive. Based on recent experimental and theoretical findings, we constructed a neural circuit model where dopamine neuronal populations receive differential inputs from individual rewards and encode heterogeneous reward prediction errors, which train cortical and striatal neurons to learn reward-associated state representation and value. Learning is achieved via simultaneous alignments of the cortical and striatal downstream connections to the mesocorticolimbic dopamine projections, and inhibition-dominance in the cortical recurrent network is a key for successful learning. Excessive excitation, whether pre-existing or induced by manipulations, leads to aberrant activity, which disrupts the alignments and even causes anti-alignment. This impairs both reward-specific motivational control and credit assignment, potentially explaining the negative and positive symptoms of schizophrenia, respectively. Our model thus provides a mechanistic account for schizophrenia, integrating the different causes and symptoms, with testable predictions.

neuroscience↗

bioRxiv2025

Structural mechanisms for the recruitment of factor H by Streptococcus pyogenes

The major bacterial pathogen Streptococcus pyogenes (Group A Streptococcus, or Strep A) recruits the negative regulator of the alternative complement pathway factor H (FH) to its surface. Antigenically sequence variable regions of several Strep A M proteins, including M5 and M6, bind FH but have no obvious sequence homology. A second Strep A surface-localized protein, FbaA, binds FH through a purported coiled-coil region, suggesting mimicry of the well-known coiled coil of M proteins. We determined the structures of fragments of M5 protein, M6 protein, and FbaA complexed with FH domains 6 and 7 (FH(6-7)). M5 and M6 proteins formed dimeric -helical coiled coils, as expected, while FbaA instead consisted of a monomeric three-helix bundle preceded by a loop. FH(6-7) accommodated different binding modes in these three proteins, with very few common interacting amino acids. Based on contributions to binding, distinct FH-binding sequence patterns were constructed for M5 and M6 proteins, enabling identification of FH-binding sequences in M or M-like Enn proteins in 32 strains of differing M types. While FbaA was allelically sequence variable, its critical FH-binding amino acids were absolutely conserved in 95 strains of differing M types. Together, FH-binding sequences were identified in about half of the known 250 Strep A strains, with the majority due to FbaA. Our structural and functional elucidation of the mechanism of FH recruitment is applicable to precise investigation of its role in Strep A virulence.

biochemistry↗

bioRxiv2025

A Novel Phosphatase Reverses the Leloir Pathway to Promote Tagatose Synthesis from Glucose

D-Tagatose is a natural, low-calorie, rare monosaccharide that has gained substantial interest as an alternative sweetener. It offers numerous benefits, including a low glycemic index, prebiotic properties, and the ability to lower blood sugar levels. Currently, tagatose is primarily produced industrially through the isomerization of galactose, utilizing both chemical and enzymatic catalysis. While these established processes can produce tagatose, they are inefficient and expensive. Recent works have demonstrated alternative biosynthetic routes to produce D-tagatose but suffer from low theoretical yield and/or reliance on expensive feedstocks. This study demonstrates a novel biochemical pathway to produce D-tagatose directly from glucose using a whole-cell process with Escherichia coli. This process is distinct from other biosynthetic schemes and utilizes a newly discovered galactose-1-phosphate-selective phosphatase to drive the native Leloir pathway in reverse and synthesize the substrate D-galactose directly from D-glucose. Our analysis of the phosphatase reveals how an ensemble of intermolecular hydrogen bonds governs substrate specificity. By co-expressing this phosphatase and an L-arabinose isomerase in a modified strain background, we demonstrate production of tagatose directly from glucose. In initial studies, we generated [~]10.5 g/L galactose from 30 g/L glucose (35 % yield) while also producing > 1 g/L tagatose. This demonstrates the feasibility of a novel approach to tagatose production in vivo with a theoretical pathway yield of 94.9 %, which is substantially higher than previously proposed tagatose biosynthetic schemes.

bioengineering↗

bioRxiv2025

What's next for Indian Ornithology? 101 key research questions

India has a rich history of ornithology, and bird research in this field has expanded considerably in recent decades, spurred by a growing number of birdwatchers and ornithologists. Despite this progress, critical gaps remain. This paper highlights key areas where further research is needed and identifies pressing questions that will shape Indian ornithology in the coming years. Drawing from diverse inputs, we present a curated list of 101 research questions spanning across the various disciplines in ornithology - Natural History, Physiology and Disease Ecology, Behaviour, Population and Community Ecology, Habitat Ecology, Macroecology and Biogeography, Population Genetics and Evolution, Applied/Economic Ornithology and Conservation. The list was compiled through a multi-stage process, starting with a public open call for questions, followed by review and curation by a smaller panel of subject specialists. Each question was independently scored by a panel of experts based on three criteria: generality, novelty, and relevance. To account for variation in scoring styles, scores were normalised using Z-scores. The top 101 research questions were then selected based on these standardised scores. Each question is accompanied by an annotation that describes the significance of the question, and highlights opportunities to address it. While our list of research questions highlights significant research priorities, it is not intended to be exhaustive. Rather, it reflects the perspectives of those involved in its curation, who deemed these questions particularly relevant and impactful towards advancing Indian ornithology. We expect these questions to spark new project ideas among students, researchers, and citizen scientists, while guiding funders, managers, and policymakers toward priority research areas.

ecology↗

bioRxiv2025

Non-invasive brain stimulation protects cognitive impairment in i.c.v.STZ injected rats: role of adult neurogenesis

In Alzheimers like dementia, neurodegeneration and synaptic dysfunction is known to the critical player in explaining the cognitive impairment. Adult neurogenesis, normally a chronic and quite process is explained to have potential in the field of Alzheimers therapy. Previous research on the non-invasive brain stimulation showed that controlling pattern of stimulation externally we can regulate/ entrain neuronal activity, possibly altering the structural changes in the circuit level. However, literature investigating if non-invasive brain stimulation could hold any potential to initiate process of adult neurogenesis are scarce. In the present study, with the use of behavioural, microscopic and biochemical tools we found that extremely low frequency magnetic field at an intensity of 17.96{micro}T with sinusoidal wave of 50Hz for 2hr daily for a period of two week in streptozotocin induced animal model of sporadic Alzheimers disease can cause improvement in spatial and reference memory, influencing their swimming strategy in water maze. Which is caused by stimulation in immature neural pluripotent stem cells, with additional redox balance and mitigation of glial aggravation in brain areas like olfactory bulb, prefrontal cortex and hippocampus. These changes were accompanied by neuroprotection as observed in the granular layer of dentate gyrus. Taken together, present study explains plausible mechanism of action on protection of neurodegeneration in Alzheimers disease through non-invasive brain stimulation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/666022v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@bc7830org.highwire.dtl.DTLVardef@176cc01org.highwire.dtl.DTLVardef@4b869dorg.highwire.dtl.DTLVardef@72e703_HPS_FORMAT_FIGEXP M_FIG Graphical illustration representing external magnetic field causing cognitive improvement eliciting adult neurogenesis in animal model of Alzheimers disease C_FIG

neuroscience↗

bioRxiv2025

Nutritional Triggers of PCOS and NAFLD: A Comparative Analysis of Diets in Female C57BL/6J Mice

ObjectiveObesity is a key factor in the development of Polycystic Ovary Syndrome (PCOS) and Non- alcoholic fatty liver disease (NAFLD). Its relationship with reproductive health and metabolic disorders remains an area of interest. Here we aimed to study the effects of two different obesogenic diets in female C57BL/6J mice on their metabolic and reproductive function. MethodsFemale C57BL/6J mice were fed high-fat high-sugar (HFHS) (45% fat and 10% sugar) diet and High fat diet (60% fat) for 21 weeks to investigate the effects on metabolic health and reproductive health. Mice were assessed for body weight, abdominal circumference, glucose tolerance (OGTT) and estrous cyclicity. At the end of the study biochemical analysis was done on isolated serum and, histological assessment of organs including liver and ovarian tissue was done to score for cystic follicle development and steatosis respectively. ResultsMice on the HFHS diet did not gain weight but developed dyslipidaemia, abnormal liver enzyme levels and severe hepatic steatosis. They did not show impaired glucose tolerance and did not develop any PCOS-like ovarian morphology indicating hepatic metabolic disturbances without significant impact on reproductive health. In contrast, mice on the 60% high-fat diet (HFD) showed marginal increase in body weight and developed altered estrous cyclicity and PCOS-like ovarian morphology. They also exhibited impaired glucose tolerance and insulin resistance, confirming a metabolic disturbance associated with PCOS. These mice did not develop significant liver fibrosis, suggesting a more specific impact on the ovaries and glucose metabolism. Our findings suggest that diet composition plays a crucial role in determining the specific metabolic and reproductive outcomes in obesity-related disorders in females.

physiology↗

bioRxiv2025

Controlling spatio-temporal sequences of neural activity by local synaptic changes

The neural basis of behavior is believed to consist of sequential patterns of neural activity in the relevant brain regions. Behavioral flexibility also requires neural circuit mechanisms that support dynamic control of sequential activity. However, mechanisms to control and reconfigure sequential activity have received little attention. Here, we show that recurrently connected networks with heterogeneous connectivity and a smooth spatial in-degree landscape (which may arise due to asymmetric neuron morphologies) provide a robust mechanism to evoke and control sequential activity. By modulating the synaptic strength of only a few neurons in local neighborhoods, we uncovered high-impact locations which can start, stop, extend, gate, and redirect sequences. Interestingly, high-impact locations coincide with mid in-degree regions. We demonstrate that these motifs can flexibly reconfigure sequential activity, and hence, provide a framework for fast and flexible computations on behavioral time scales, while the individual parts of the pathways remain rigid and reliable.

neuroscience↗

bioRxiv2025

DNA Conformational Flexibility Descriptors Improve Transcription Factor Binding Prediction Across the Protein Families

Precise binding of transcription factors (TFs) to specific DNA sequences is fundamental to gene regulation, yet the molecular principles underpinning TF-DNA specificity remain incompletely understood. While nucleotide sequence and DNA shape are known determinants of TF binding, the role of DNA flexibility encompassing axial, torsional, and stretching dynamics-- remains largely unexplored, particularly across diverse TF families. Here, we systematically integrate experimentally and computationally derived DNA flexibility descriptors into predictive models of TF-DNA binding specificity. Through extensive analyses of large-scale in vitro datasets from HT-SELEX, SELEX-Seq, protein binding microarrays encompassing mam-malian and Drosophila TFs, we demonstrate that flexibility-augmented models consistently outperform sequence based models, and DNA shape augmented models to an extent. These improvements are robust across diverse experimental platforms, and scale of the datasets, underscoring the importance of DNA conformational dynamics in indirect readout. Quantitative analyses of position-specific flexibility contributions reveal distinct "flexibility hotspots" within transcription factor binding sites and their flanking regions. This is exemplified by structural insights into the homeodomain TF MSX1, where localized DNA bendability directly correlates with enhanced binding affinity and precise recognition specificity. Finally, leveraging in vivo ChIP-Seq and DNase-Seq data from ENCODE, we further validate that DNA flexibility substantially enhances the identification of functional TF binding sites across various TF families and cellular contexts. Collectively, current findings substantiate DNA flexibility as a fundamental element of the cis-regulatory code and significantly advancing predictive frameworks of gene regulatory networks.

bioinformatics↗

bioRxiv2025

Low Angle Ring Illumination Stereomicroscopy (LARIS): A high-resolution imaging method of compound eyes in Drosophila and other insects.

The compound eyes of Drosophila are widely used to gain valuable insights into genetics, developmental biology, cell biology, disease biology, and gene regulation. Various parameters, such as eye size, pigmentation loss, formation of necrotic patches, and disorientation, fusion or disruption of ommatidial arrays are commonly assessed to evaluate eye development and degeneration. In this study, we developed an improved optical alignment imaging technique named "Low Angle Ring Illumination Stereomicroscopy" (LARIS), which provides high-contrast images of the Drosophila compound eye. By capturing images of the same eye using different optical alignments of the stereomicroscope, we achieved the highest resolution with minimal reflection through the LARIS method. The images captured using LARIS clearly show ommatidial fusion, disorientation, and pigmentation loss in the Drosophila eye compared to those obtained with conventional imaging method. We believe that LARIS will open new avenues for improved imaging of the compound eyes of Drosophila and other insects.

cell biology↗

bioRxiv2025

A conserved mechanism of membrane fusion in nuclear pore complex assembly

The nuclear pore complex (NPC) forms a large channel that spans the double lipid bilayer of the nuclear envelope and is the central gateway for macromolecular transport between the nucleus and cytoplasm in eukaryotes. NPC biogenesis requires the coordinated assembly of over 500 proteins culminating in the fusion of the inner and outer nuclear membranes. The molecular mechanism of this membrane fusion step that occurs in all eukaryotes is unknown. Here, we elucidate the mechanism by which two paralogous transmembrane proteins, Brl1 and Brr6, mediate membrane fusion in S. cerevisiae. Both proteins form multimeric, ring-shaped complexes with membrane remodeling activity. Brl1 is enriched at NPC assembly sites via a nuclear export sequence and then interacts with Brr6 across the nuclear envelope lumen through conserved hydrophobic loops. Disrupting this interaction blocks fusion and halts NPC assembly. Molecular dynamics simulations suggest that the Brl1-Brr6 complex drives membrane fusion by forming a channel across bilayers that enables lipid exchange. Phylogenetic analyses reveal that Brl1/Brr6 homologues are broadly distributed across eukaryotes, and functional experiments in human cells and D. melanogaster establish CLCC1 as an NPC fusogen in metazoans. Together, our results uncover a novel, conserved mechanism for membrane fusion in eukaryotes.

cell biology↗

bioRxiv2025

Pervasive noise in human splice site selection

RNA splicing has historically been thought to be highly efficient and accurate, with little opportunity for deviation from regulated alternative splicing decisions. This dogma has been challenged by recent observations that suggest that biological noise may contribute substantially to transcriptome diversity. However, quantitative understanding of stochastic variations in splicing is challenging because these transcripts are likely subject to rapid degradation. Here, we use ultra-deep sequencing across RNA compartments to track splicing intermediates in human cells and see abundant cryptic splicing associated with genomic features that promote splicing noise. We observe pervasive usage of low-fidelity splice sites, likely due to stochasticity in recruitment or binding of the spliceosome. These sites are most likely degraded in the nucleus rather than targeted by translation-dependent degradation processes, suggesting widespread surveillance and rapid quality control of non-productive RNA transcripts. Our findings provide unprecedented insights into the propensity for error in RNA processing mechanisms and the regulation of alternative splice sites across a gene.

genomics↗

bioRxiv2025

Biophysically relevant network model of the piriform cortex predicts odor frequency encoding using network mechanisms

Olfactory-guided animals utilize fast concentration fluctuations in turbulent odor plumes to perceive olfactory landscapes. Recent studies have demonstrated that the olfactory bulb (OB) encodes such temporal features present in natural odor stimuli. However, whether this temporal information is encoded in the piriform cortex (PCx) remains unknown. Hence, we developed a biophysically relevant PCx network model and simulated it using previously recorded in vivo activities of mitral and tufted cells in response to 2Hz and 20Hz odor frequencies for three stimulus mixtures. Analysis of single-cell activity across trials revealed that individual pyramidal neurons (PYRs) were largely ineffective at discriminating between 2Hz and 20Hz. However, the trial-averaged activity of the PYR population could discriminate between the two frequencies significantly. Moreover, using log-likelihood scores we further discovered that odor frequency discrimination happened through a highly distributed mechanism among the PYRs. One-dimensional convolutional neural network models trained and tested on PYRs activities achieved discrimination accuracies up to 95%. Using virtual synaptic knockout models, we found that eliminating either feedback or feedforward inhibition onto PYRs improved the decoding accuracy across all odor conditions. Conversely, eliminating recurrent excitation among PYRs or simultaneously eliminating recurrent inhibition within both interneuron populations degraded decoding performance. Removing recurrent connections within individual interneuron populations had minimal effects on the performance. Overall, our PCx model demonstrates that it can discriminate between 2Hz and 20Hz odor stimuli, with a bidirectional capability of performance modulation by specific circuit motifs. These findings predict that the piriform cortex encodes and processes temporal features of odor stimuli. New & NoteworthyWe simulated the first biophysically relevant network model of the piriform cortex (PCx) to show differential encoding of odor frequencies at 2Hz and 20Hz. 1D convolutional neural networks demonstrated a distributed role of pyramidal neurons in the encoding. Surprisingly, eliminating feedforward or feedback inhibition improves frequency discrimination, while eliminating recurrency impairs it. Specific circuit motifs, not just baseline activity levels, determine odor frequency representation. Overall, our results predict the PCxs capacity for temporal odor processing.

neuroscience↗