Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.02.28.640652

Heterogeneous monotonic and non-monotonic responses to odor in mitral/tufted glomeruli of the mouse olfactory bulb

Subramanian, N.·Wharton, D.·Karamched, B. R.·Bertram, R.·Storace, D. A.
View original source ↗Export metadata ↓

Abstract

Animals can recognize and discriminate between different odors and the same odor over a range of concentrations. Processing within the mouse olfactory bulb (OB) may be involved, yet the underlying mechanisms remain unclear. Each olfactory receptor neuron (ORN) type maps to the OB in olfactory receptor specific channels called glomeruli where they connect with the dendrites of mitral/tufted cells (MTCs), which project their axons to the rest of the brain. Differences between input and output define the functions carried out by a brain region. Using in vivo dual-color 2-photon Ca2+ imaging from the ORNs and MTCs innervating the same glomeruli in the mouse OB, we identified a novel MTC response type with a non-monotonic concentration-response relationship. We used mathematical modeling to demonstrate that non-monotonic response types are consistent with a form of interglomerular processing, which we propose is a mechanism to facilitate odor discrimination and the ability to achieve concentration-invariant odor perception. Graphical AbstractThe olfactory bulb input-output transformation was imaged using dual-color 2-photon imaging. (Top) Cartoon and histological examples of labeling the olfactory bulb input and output using spectrally distinct optical sensors. (Middle) Modeling and experimental work reveal that input neurons that respond with primarily monotonic concentration-response relationships are transformed into a mix of monotonic and non-monotonic responses. (Bottom) Olfactory bulb output state space for a population of 3 glomeruli with exclusively monotonic responses (black), and with both monotonic and non-monotonic responses (red). Each trajectory represents a cloud of points that reflects variations in the fluctuations of molecular components present in natural odor stimuli. Monotonic responses alone cluster together, while multiple response types broaden coverage of MTC state space. Greater coverage of state space makes it easier to discriminate one odor from another, even though the dimension of olfactory bulb state space is larger than 3. Key PointsO_LIAlthough the olfactory bulb is the first stage of olfactory sensory processing, its role in transforming sensory information remains poorly understood. C_LIO_LIDifferent olfactory receptor neuron types map to the olfactory bulb in olfactory receptor specific channels called glomeruli, where they interact with the dendrites of mitral/tufted cells, which project to the rest of the brain. C_LIO_LIWe used dual-color 2-photon Ca2+ imaging to image the input-output transformation olfactory receptor neuron (ORN) and mitral/tufted (MTC) glomeruli across a wide concentration range. C_LIO_LIThe ORN input to all tested glomeruli responded to increasing concentration changes with monotonic increases, while the corresponding MTCs outputs of each glomerulus responded with monotonic and non-monotonic changes. C_LIO_LIThe results were consistent with a mathematical model of the olfactory bulb incorporating feed-forward and lateral inhibition. C_LI

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Subramanian, N., Wharton, D., Karamched, B. R., Bertram, R., Storace, D. A.. 2025-03-06. Heterogeneous monotonic and non-monotonic responses to odor in mitral/tufted glomeruli of the mouse olfactory bulb. https://doi.org/10.1101/2025.02.28.640652

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Isogenic forebrain organoids uncover early neurodevelopmental alterations and imbalances in neuronal function leading to hyperexcitation in Gaucher disease

Gaucher disease is a rare lysosomal storage disorder caused by autosomal recessive mutations in the GBA1 gene, encoding the lysosomal enzyme glucocerebrosidase. Gaucher disease is classified in 3 different subtypes depending on the presence and severity of neurological involvement, with type 2 resulting in fatal early-onset neuropathology and patients exhibiting developmental delays, seizures and early death. Studies investigating disease mechanisms of neuronopathic Gaucher disease are mainly based on animal models and focus predominantly on late neuronal phenotypes. Here, we established healthy control and Gaucher disease patient-derived iPSC lines and engineered them to obtain isogenic control and disease lines. Using these lines, we generated cortical and subpallial brain organoids in which we identified early-onset lipid dysregulation in form of glucosylceramide accumulation, highly elevated glucosylsphingosine, and a later increase in ganglioside levels, recapitulating clinical findings. Furthermore, single-cell transcriptomic profiling uncovered novel phenotypes in both cortical and subpallial forebrain organoids. Subpallial alterations consisted of an early increase in migrating interneurons in subpallial organoids, which upregulated cholesterol metabolism. Cortical alterations showed early upregulation of mitochondrial genes and a downregulation of proliferation, with a subsequent switch from GABAergic to glutamatergic neuron fate with a striking increase in gene expression related to the synaptic assembly. Functional assays demonstrated a marked hyperexcitability of cortical organoids and reduced response to GABA-A receptor blockage in Gaucher disease. Additional 2D neuronal network models confirmed the organoid data and showed that both glutamatergic and GABAergic neurons contribute to the phenotype, with hyperexcitability of Gaucher glutamatergic neurons and incapacity of Gaucher GABAergic neurons to balance the excessive excitation. This alteration represents a clinically significant phenotype as many patients exhibit an excitation/inhibition imbalance leading to treatment-resistant seizures, hastening their decline. In conclusion, our defined human models of Gaucher disease identify novel and clear phenotypes that can be used for drug screening or aid in development of new therapeutic strategies to ameliorate Gaucher disease.

neuroscience↗
bioRxiv2026

Oxytocin and Vasopressin Immunoreactivity Differs Across Auditory Brainstem Nuclei in Rodents with Distinct Social Systems

Oxytocin (OT) and vasopressin (AVP) are neuropeptide hormones involved in regulating animal social behavior and a broad spectrum of physiological processes. Although their distributions are well documented in neuroendocrine regions of the forebrain and midbrain, their expression in the hindbrain remains poorly understood. Here, we used immunohistochemistry to quantify OT and AVP immunoreactive puncta within three auditory brainstem nuclei, the lateral superior olive (LSO), the medial superior olive (MSO), and the medial nucleus of the trapezoid body (MNTB) in six wild-caught rodent species differing in sociality. We also quantified the volume of these nuclei and examined variation in total brain volume across species and sociality. OT and AVP puncta count differed among species and social groups. Group-living species exhibited higher OT and AVP puncta counts than monogamous and solitary species in the LSO and MNTB. In the MSO, OT puncta counts did not differ among social groups, whereas AVP puncta counts were higher in group-living than in monogamous and solitary species. Total brain volume and the volumes of the MNTB and MSO differed among species, but not across social groups, whereas LSO volume did not differ among species or sociality. These findings revealed sociality-related variation in OT and AVP immunoreactive puncta within auditory brainstem circuits and suggest that neuropeptide signaling within early auditory brainstem pathways may contribute to the neural integration of social and auditory information.

neuroscience↗
bioRxiv2026

Connexin 40 deficiency alters the temporal profile of postictal oxygen dynamics following focal seizures.

Epilepsy is increasingly recognized as a disorder involving both neuronal and vascular dysfunction. While connexin signaling has been implicated in epileptogenesis, the contribution of vascular connexins to seizure associated cerebrovascular pathology remains poorly understood. Connexin40 (Cx40) is an endothelial gap junction protein that plays a crucial role in vascular communication and blood-flow regulation. Seizures induce dynamic changes in cerebral perfusion and oxygenation, including prolonged postictal hypoperfusion/hypoxia. To determine whether Cx40 influences postictal hypoxia following focal seizures, we examined seizure characteristics and postictal oxygen dynamics in Cx40 knockout (Cx40-/-) mice using an established focal hippocampal seizure model. Electrically kindled seizures were elicited in wild-type and Cx40-/- mice, and local hippocampal tissue oxygenation was continuously monitored before and after seizure induction. Seizure duration did not differ between genotypes, indicating comparable seizure severity. Interestingly, Cx40 deletion altered the temporal pattern of postictal oxygen recovery, producing greater early hypoxia and a delayed secondary rebound in pO2 despite similar peak oxygen levels and overall hypoxic burden. These findings demonstrate that loss of Cx40 selectively alters the temporal profile of postictal oxygen dynamics without affecting seizure duration. Taken together, the results suggest that endothelial gap junctional communication contributes to postictal vascular recovery and identify Cx40 as a potential modulator of seizure associated neurovascular dysfunction.

neuroscience↗