Biology subjects

Albeanu, D. F.

Publications and source records attributed to Albeanu, D. F..

8 recordsLinked to original sources

bioRxiv2025

Axially decoupled photo-stimulation and two photon readout (ADePT) for mapping functional connectivity of neural circuits

All-optical in vivo physiology enables three-dimensional interrogation of neural circuits function. Here, we introduce ADePT (Axially-Decoupled Photo-stimulation and Two-photon readout), a strategy that combines flexible optogenetic stimulation with neural activity imaging. ADePT achieves axially contained widefield patterned stimulation by coupling a digital micro-mirror device illuminated by a solid-state laser to a motorized holographic diffuser, while in parallel performing multiphoton imaging across different z-planes. As a proof of principle, we apply ADePT to map excitatory and inhibitory functional connectivity in the mouse early olfactory system. By controlling activity in individual glomeruli on the olfactory bulb surface and recording responses from output mitral and tufted cells in deeper layers, we identify cohorts of sister cells driven by the same parent glomerulus and analyze their distinct connectivity patterns. We further report specificity in the inhibitory circuitry, as we find that GABAergic/dopaminergic (DAT+) interneurons associated with different glomeruli selectively suppress baseline and odor-evoked activity in distinct mitral and tufted cell populations. Together, these results establish ADePT as a platform for high-throughput functional connectivity mapping in optically accessible brain regions.

neuroscience↗

bioRxiv2025

An evolutionarily conserved mechanism for reformatting odor concentration in early olfactory circuits

Understanding how stimuli from the sensory periphery are progressively reformatted to yield useful representations is a fundamental challenge in neuroscience. In olfaction, assessing odor concentration is key for many behaviors, such as tracking and navigation. Initially, as odor concentration increases, the average response of first-order sensory neurons also increases. However, the average response of second-order neurons remains flat with increasing concentration - a transformation that is believed to help with concentration-invariant odor identification, but that seemingly discards concentration information before it could be sent to higher brain regions. By combining neural data analyses from diverse species with computational modeling, we propose strategies by which second-order neurons preserve concentration information, despite flat mean responses at the population level. We find that individual second-order neurons have diverse concentration response curves that are unique to each odorant -- some neurons respond more with higher concentration and others respond less -- and together this diversity generates distinct combinatorial representations for different concentrations. We show that this encoding scheme can be recapitulated using a circuit computation, called divisive normalization, and we derive sufficient conditions for this diversity to emerge. We then discuss two mechanisms (spike rate vs. timing based) by which higher order brain regions may decode odor concentration from the reformatted representations. Since vertebrate and invertebrate olfactory systems likely evolved independently, our findings suggest that evolution converged on similar algorithmic solutions despite stark differences in neural circuit architectures. Finally, in land vertebrates a parallel olfactory pathway has evolved whose second-order neurons do not exhibit such diverse response curves; rather neurons in this pathway represent concentration information in a more monotonic fashion on average, potentially allowing for easier odor localization and identification at the expense of increased energy use.

neuroscience↗

bioRxiv2023

Fast updating feedback from piriform cortex to the olfactory bulb relays multimodal reward contingency signals during rule-reversal

While animals readily adjust their behavior to adapt to relevant changes in the environment, the neural pathways enabling these changes remain largely unknown. Here, using multiphoton imaging, we investigated whether feedback from the piriform cortex to the olfactory bulb supports such behavioral flexibility. To this end, we engaged head-fixed mice in a multimodal rule-reversal task guided by olfactory and auditory cues. Both odor and, surprisingly, the sound cues triggered cortical bulbar feedback responses which preceded the behavioral report. Responses to the same sensory cue were strongly modulated upon changes in stimulus-reward contingency (rule reversals). The re-shaping of individual bouton responses occurred within seconds of the rule-reversal events and was correlated with changes in the behavior. Optogenetic perturbation of cortical feedback within the bulb disrupted the behavioral performance. Our results indicate that the piriform-to-olfactory bulb feedback carries reward contingency signals and is rapidly re-formatted according to changes in the behavioral context.

neuroscience↗

bioRxiv2021

Wiring logic of the early rodent olfactory system revealed by high-throughput sequencing of single neuron projections

The structure of neuronal connectivity often provides insights into the relevant stimulus features, such as spatial location, orientation, sound frequency, etc1-6. The olfactory system, however, appears to lack structured connectivity as suggested by reports of broad and distributed connections both from the olfactory bulb to the piriform cortex7-22 and within the cortex23-25. These studies have inspired computational models of circuit function that rely on random connectivity26-33. It remains, nonetheless, unclear whether the olfactory connectivity contains spatial structure. Here, we use high throughput anatomical methods (MAPseq and BARseq)34-38 to analyze the projections of 5,309 bulb and 30,433 piriform cortex output neurons in the mouse at single-cell resolution. We identify previously unrecognized spatial organization in connectivity along the anterior-posterior axis (A-P) of the piriform cortex. We find that both the bulb projections to the cortex and the cortical outputs are not random, but rather form gradients along the A-P axis. Strikingly, these gradients are matched: bulb neurons targeting a given location within the piriform cortex co-innervate extra-piriform regions that receive strong inputs from neurons within that piriform locus. We also identify signatures of local connectivity in the piriform cortex. Our findings suggest an organizing principle of matched direct and indirect olfactory pathways that innervate extra-piriform targets in a coordinated manner, thus supporting models of information processing that rely on structured connectivity within the olfactory system.

neuroscience↗

bioRxiv2020

A non-canonical feedforward pathway for computing odor identity

Elucidating neural circuits that enable robust odor identification remains a fundamental challenge in olfaction. The current leading model states that odor identity is computed within the piriform cortex (PC), drawing from mitral cell input from the olfactory bulb. Here we find that tufted cells, the other principal cell-type of the bulb, which strongly innervate the anterior olfactory nucleus (AON) instead, substantially outperform mitral cells in decoding both odor identity and intensity, acting in a largely feedforward fashion. Cortical feedback from PC specifically restructures mitral cell responses, while feedback from AON preferentially controls the gain of tufted cell odor representations, matching biases in feedforward connectivity. Leveraging cell-type specific analyses, we identify a non-canonical feedforward pathway for odor recognition and discrimination mediated by the tufted cells, and propose that bulb target areas, other than the piriform cortex, such as AON and olfactory striatum, are well-positioned to compute odor identity.

neuroscience↗

bioRxiv2018

Olfactory marker protein regulates refinement of the glomerular map

The olfactory glomerulus is the anatomical and functional unit of the olfactory bulb, defined by convergent input from olfactory sensory neuron (OSN) axons expressing the same type of odorant receptor (OR). A key marker of mature OSNs is the olfactory marker protein (OMP), whose deletion has been associated with deficits in OSN signal transduction and odor discrimination. Here, we have investigated glomerular odor responses and anatomical architecture in mice in which one or both alleles of OMP were replaced by the fluorescent synaptic activity reporter, synaptopHluorin (OMP+/- and OMP-/- mice, respectively). Functionally heterogeneous glomeruli, that is, ones with micro-domains with distinct odor responses were rare in OMP+/- mice, but occurred frequently in OMP-/- mice. Genetic targeting of single ORs revealed that these micro-domains arise from anomalous co-innervation of individual glomeruli by OSNs expressing different ORs. The glomerular mistargeting of OSNs in the absence of OMP is restricted to a local neighborhood of a few glomerular diameters. Our studies document functional heterogeneity in sensory input within individual glomeruli and uncover its anatomical correlate, revealing an unexpected role for OMP in the formation and refinement of the glomerular olfactory map.

neuroscience↗

bioRxiv2018

Mosaic representations of odors in the input and output layers of the mouse olfactory bulb

The elementary stimulus features encoded by the olfactory system remain poorly understood. We examined the relationship between 1,666 physical-chemical descriptors of odors and the activity of olfactory bulb inputs as well as outputs in awake mice. Glomerular and M/T cell responses were sparse and locally heterogeneous, with only a coarse dependence of glomerular positions on physical-chemical properties. Odor features represented by ensembles of M/T cells were overlapping, but distinct from those represented in glomeruli, consistent with extensive interplay between feedforward and feedback inputs to the bulb. This reformatting was well-described as a rotation in odor space. The descriptors accounted for a small fraction in response variance, and the similarity of odors in physical-chemical space was a poor predictor of similarity in neuronal representations. Our results suggest that commonly used physical-chemical properties are not systematically represented in bulbar activity and encourage further search for better descriptors of odor space.

neuroscience↗

bioRxiv2017

A High Resolution Whole Brain Imaging Using Oblique Light Sheet Tomography

Present light sheet fluorescence microscopes lack the wherewithal to image the whole brain (large tissues) with uniform illumination/detection parameters and high enough resolution to provide an understanding of the various aspects of neuroanatomy. To overcome this, we developed an oblique version of the light sheet microscope (Oblique Light Sheet Tomography, OLST) that includes a high magnification objective and serial sectioning, for volumetric imaging of the whole mouse brain at high spatial resolution at constant illumination/detection. We developed a novel gelatin based re-embedding procedure that makes the cleared brain rigid so that it can sectioned using our integrated microtome. Here, we characterize OLST and show that it can be used to observe dendritic morphology, spines and follow axons over a few mm in the mouse brain.

neuroscience↗