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Abraham, N. M.

Publications and source records attributed to Abraham, N. M..

8 recordsLinked to original sources

Vascular tree structure-based perfusion phantom fabrication using modified Hele-Shaw Cell technique

Tissue phantoms that mimic microvasculature and perfusion are essential for modelling vascular function, guiding interventions, and calibrating imaging systems, which require faithful replication of vascular geometry and flow. Conventional fabrication strategies, including wire-based molding, lithographic micromachining, and additive manufacturing, offer useful capabilities but remain constrained by predefined designs, rectangular channel cross-sections, limited scalability, and high production costs. Reliance on predefined digital vascular models restricts design flexibility and limits the ability to capture the natural variability and complexity of real vascular systems. Here, we present a lithography-free, fractal-generating approach based on a modified Lifted Hele-Shaw Cell (LHSC) technique, in which vascular networks emerge spontaneously via interfacial fluid instabilities. Unlike pre-designed methods, these structures are governed by fluid properties and flow conditions, enabling adaptive, physiologically relevant geometries with smooth Gaussian cross-sections and natural diameter tapering. We demonstrate four phantom designs: a planar vascular tree, an anatomically guided cerebral network, a retinal vascular model, and a conformable curved substrate phantom. Validation using Laser Speckle Contrast Imaging confirms structural fidelity and physiologically relevant flow consistent with Murrays law. This platform uniquely integrates realistic vascular architecture with emergent, fractal driven formation, highlighting its potential as a reproducible and biologically relevant alternative to conventional vascular phantom fabrication. Furthermore, the availability of such realistic in vitro vascular models can reduce reliance on animal experiments and contribute towards more ethical and sustainable preclinical research.

bioengineering↗

Decision revisions modulated by synaptic inhibition in the olfactory bulb facilitate learning

Behavioral responses are preceded by decisions based on perceived sensory evidence. In real life, sensory inputs are often noisy and change incessantly, raising the question of when and how accurate decisions are made. Cognitive flexibility allows us to revise the choices in case of perceptual conflicts, leading to response revisions. This involves switching between available choices or rapidly stopping misconstrued responses. Here, we quantified these erroneous behavioral actions and studied the underlying neural mechanisms. Mice were trained on an olfactory decision-making task wherein they had to distinguish between a rewarded and an unrewarded stimulus by responding with a lick or withholding it. While the animals respond by licking for both rewarded and unrewarded odor stimuli at the initial stages of learning, the responses almost disappear for the unrewarded ones in the learned stage. However, animals tend to initiate lick responses and stop within a few milliseconds for a few unrewarded trials, even when accuracy levels are high. We describe this phenomenon as decision revisions (DR), and observed it in 5-25% of trials among high-performance blocks. These revisions were mostly observed within a few hundred milliseconds of stimulation. We observed a significantly higher number of revision trials for binary odor mixture discriminations compared to monomolecular ones. Further, by enhancing inhibitory synaptic signaling in the olfactory bulb through photoactivation of ChR2-expressing GAD65-positive GABAergic interneurons, we observed faster odor discrimination and fewer revision trials. Thus, our findings confirm decision revisions that are stimulus complexity-dependent and the pre-cortical control over such a complex cognitive activity. Highlights of the studyO_LIMice revise context-inappropriate responses in a Go/No-go task. C_LIO_LIMice correct errors as they learn. C_LIO_LIDecision revisions are shaped by stimulus complexity. C_LIO_LIOptogenetic activation of the olfactory bulb inhibitory interneurons modulates decision revisions. C_LI

neuroscience↗

Synaptic inhibition in the accessory olfactory bulb regulates pheromone location learning and memory

Pheromone signaling is pivotal in driving the social and reproductive behaviors of rodents. Learning and memorizing the pheromone locations involve olfactory subsystems. To study the neural basis of this behavior, we trained female heterozygous knockouts of GluA2 (AMPAR subunit) and NR1 (NMDAR subunit), targeting GAD65 interneuron population, in a pheromone location learning assay. We observed impaired memory of pheromone locations on early and late recall periods, pointing towards the possible role of ionotropic glutamate receptors (iGluRs), and thereby the synaptic inhibition in pheromone location learning. Correlated changes were observed in the expression levels of activity-regulated cytoskeletal (Arc) protein, which is critical for memory consolidation, in the associated brain areas. Further, to probe the involvement of the main and accessory olfactory bulbs (MOB and AOB) in pheromone location learning, we knocked out GluA2 and NR1 from MOB and/or AOB neuronal circuits by stereotaxic injection of Cre-dependent AAV5 viral particles. Perturbing the inhibitory circuits of MOB and AOB or AOB-alone resulted in the pheromone location memory deficits. These results confirm the role of iGluRs and the synaptic inhibition exerted by the interneuron network of AOB in regulating learning and memory of pheromone locations.

neuroscience↗

Mouse olfactory system acts as anemo-detector and -discriminator

Airflow detection while smelling is a fundamental requirement for olfaction, yet the mechanisms underlying such multimodal processing in the olfactory system remain unknown. We report here that mice can learn to accurately discriminate airflow with parallel processing of both mechanical and chemical stimuli revealed by modulated sniffing and refined calcium signaling in the olfactory bulb inhibitory network. Genetic perturbation of AMPAR function and optogenetic control bidirectionally shifted airflow discrimination learning pace, with contrasting phenotypes observed for odor learning, engagement of inhibitory circuits, and setting the optimal inhibition level for stimulus refinement. Multimodal odor-airflow stimuli at subthreshold levels enhanced learning, demonstrating that mechanical stimuli heighten olfactory perception. Our results, thus explain the multimodality of olfaction, and reveal an unexplored dimensionality of odor perception.

neuroscience↗

Uncertainty revealed by delayed responses during olfactory matching

Matching of olfactory stimuli involves both sensory and higher cognitive functioning. Different decision processes such as detection and discrimination, along with holding the perceived information are involved during the matching process. Accuracy and decision times, the interdependent readouts, can define the uncertainty involved in matching of sensory stimuli. To probe sensory and cognitive functions involving olfactory system in human subjects, we have developed a novel olfactory matching paradigm using an automated custom-built olfactory-action meter. With precise and consistent odor delivery and real-time data analysis, our system automates the entire process without any intervention by the experimenter, making it suitable as a diagnostic tool for quantifying olfactory and neurocognitive fitness. In around 400 healthy human subjects, with mean detection accuracy of 90%, we observed significantly better olfactory matching performance for simple monomolecular odors, in comparison to complex binary odor mixtures. Odor matching accuracy declined significantly with the increase in odor complexity. Olfactory matching was more rapid when subjects made correct versus incorrect decisions, indicating perceptual certainty. Subjects also took longer matching time for complex odors compared to simple odor stimuli. Thus, olfactory matching that provides a combined readout of sensory and cognitive fitness, establishes a direct link between the performance accuracy and the certainty of decisions.

neuroscience↗

Local postsynaptic signalling on slow time scales in reciprocal olfactory bulb granule cell spines matches asynchronous release

In the vertebrate olfactory bulb (OB), axonless granule cells (GC) mediate self- and lateral inhibitory interactions between mitral/tufted cells via reciprocal dendrodendritic synapses. Locally triggered release of GABA from the large reciprocal GC spines occurs on both fast and slow time scales, possibly enabling parallel processing during olfactory perception. Here we investigate local mechanisms for asynchronous spine output. To reveal the temporal and spatial characteristics of postsynaptic ion transients, we imaged spine and adjacent dendrite Ca2+- and Na+-signals with minimal exogenous buffering by the respective fluorescent indicator dyes upon two-photon uncaging of DNI-glutamate in OB slices from juvenile rats. Both postsynaptic fluorescence signals decayed slowly, with average half durations in the spine head of t1/2_{Delta}[Ca2+]i ~500 ms and t1/2_{Delta}[Na+]i ~1000 ms. We also analysed the kinetics of already existing data of postsynaptic spine Ca2+-signals in response to glomerular stimulation in OB slices from adult mice, either WT or animals with partial GC glutamate receptor deletions (NMDAR: GluN1 subunit; AMPAR: GluA2 subunit). In a large subset of spines the fluorescence signal had a protracted rise time (average time to peak ~400 ms, range 20 ms - >1000 ms). This slow rise was independent of Ca2+ entry via NMDARs, since similarly slow signals occurred in {Delta}GluN1 GCs. Additional Ca2+ entry in {Delta}GluA2 GCs (with AMPARs rendered Ca2+-permeable), however, resulted in larger {Delta}F/Fs that rose yet more slowly. Thus GC spines appear to dispose of several local mechanisms to promote asynchronous GABA release, which are reflected in the time course of mitral/tufted cell recurrent inhibition.

neuroscience↗

Multimodal Learning of Pheromone Locations

Memorizing pheromonal locations is critical for many mammalian species as it involves finding mates and avoiding competitors. In rodents, pheromonal information is perceived by the main and accessory olfactory systems. However, the role of somatosensation in context dependent learning and memorizing of pheromone locations remains unexplored. We addressed this problem by training female mice on a multimodal task to locate pheromones by sampling volatiles emanating from male urine through the orifices of varying dimensions or shapes that are sensed by their vibrissae. In this novel pheromone location assay, female mice preference towards male urine scent decayed over time when they were permitted to explore pheromones v/s neutral stimuli, water. On training them for the associations involving olfactory and whisker systems, it was established that they were able to memorize the location of opposite sex pheromones, when tested 15 days later. This memory was not formed either when the somatosensory inputs through whisker pad were blocked or when the pheromonal cues were replaced with that of same sex. The association between olfactory and somatosensory systems were further confirmed by the enhanced expression of the Activity regulated cytoskeleton protein. Further, the activation of main olfactory bulb circuitry by pheromone volatiles did not cause any modulation in learning and memorizing non-pheromonal volatiles. Our study thus provides the evidence for associations formed between different sensory modalities facilitating the long-term memory formation relevant to social and reproductive behaviors.

neuroscience↗

Similarity and strength of glomerular odor representations define neural metric of sniff-invariant discrimination time

The olfactory environment is first represented by glomerular activity patterns in the olfactory bulb. It remained unclear, how these activity patterns intersect with sampling behavior to account for the time required to discriminate odors. Using different classes of volatile stimuli, we investigated glomerular activity patterns and sniffing behavior during olfactory decision-making. Mice discriminated monomolecular odorants and binary mixtures on a fast time scale and learned to increase their breathing frequency at a fixed latency after trial initiation, independent of odor identity. Relative to the increase in breathing frequency, monomolecular odorants were discriminated within 10-40 ms while binary mixtures required an additional 60-70 ms. Intrinsic imaging of odor-evoked glomerular activity maps in anesthetized and awake mice revealed that the Euclidean distance between glomerular patterns elicited by different odors, a measure of similarity and activation strength, was anti-correlated with discrimination time. Therefore, the similarity of glomerular patterns and their activation strengths, rather than sampling behavior, define the extent of neuronal processing required for odor discrimination, establishing a neural metric to predict olfactory discrimination time.

neuroscience↗