Biology subjects

Mizrahi, A.

Publications and source records attributed to Mizrahi, A..

6 recordsLinked to original sources

bioRxiv2025

Olfactory Training Enhances Adult Neurogenesis of the Olfactory Epithelium Improving Odor Discriminability of the Olfactory Bulb

Olfaction enables us to detect chemicals in the environment, and its impairment affects one in four people worldwide. As the most common therapy, olfactory training involves repeated exposure to odorants restoring function in 30-50% of patients. However, the mechanisms underlying this therapy, and its partial efficacy, are unknown. By modelling olfactory training in mice, we found that odor exposure triggers quiescent neural stem cells of the olfactory epithelium to re-enter the cell cycle, enhancing neurogenesis and survival of olfactory sensory neurons. Coupling neuronal activity with stem cells proliferation, these effects scaled with odor concentration and were replicated without odorants upon chemogenetic activation of olfactory sensory neurons. Imaging mitral cells in the olfactory bulb revealed that increased neurogenesis in the olfactory epithelium enhanced odor sensitivity and discriminability. Our findings uncover activity-dependent cellular mechanisms linking peripheral nervous system regeneration to central olfactory processing, offering new avenues for treating olfactory dysfunction. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=190 HEIGHT=200 SRC="FIGDIR/small/692562v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@1a6a0b7org.highwire.dtl.DTLVardef@817a4forg.highwire.dtl.DTLVardef@84f063org.highwire.dtl.DTLVardef@1c20f8b_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTS- Olfactory training (OT) is a common clinical practice of unknown cellular mechanisms - OT in mice triggers stem cell activation and neurogenesis in the olfactory epithelium - Artificial stimulation of olfactory neurons is sufficient to trigger neural stem cell activity - Neurogenesis in the olfactory epithelium improves odor discrimination by mitral cells

cell biology↗

bioRxiv2025

Genetic architecture of the developing forelegs of Drosophila prolongata; an exaggerated weapon and ornament

Extreme secondary sexual traits are some of the most striking phenotypes in nature. Studies on the genetics of these phenotypes have largely focused on within-species functional analyses of signalling pathways. Although useful, these do not provide insight into the evolutionary mechanisms that occur during the evolution of trait exaggeration. Drosophila prolongata offers an exceptional opportunity to explore the evolution of trait exaggeration, as it is the only species in the melanogaster species group with male-specific foreleg size exaggeration under both intra- and intersexual selection. Here, we used sex-specific RNA-seq from fore- and midleg tissues during early development and after initiation of sexually dimorphic growth between these tissues in D. prolongata. We also sampled the same developmental stages in D. carrolli ([~]4MYA divergence) and D. melanogaster ([~]20MYA). Using comparisons of gene expression between sexes, species, tissues, and developmental stages, we found a positive relationship between the number, but not the magnitude of differential expression of sex-biased genes, with the extent of phenotypic dimorphism. One gene with a large effect, grain, caused D. prolongata-like leg size phenotypes in D. melanogaster legs when knocked down. We further found only modest changes to magnitude and direction of expression differences in signalling pathways previously implicated in sexually dimorphic evolution. This suggests that these pathways regulating trait expression and dimorphism but may not be primary drivers of their phenotypic evolution. Significance statementHow sexes evolve distinct forms while developing from a shared genome continues to be incompletely resolved. We explore a sexually dimorphic exaggerated trait, enlarged forelegs in Drosophila prolongata, and compare changes in sex-biased gene expression between tissues and developmental stages in D. prolongata and two closely related species without foreleg exaggeration. We show that major developmental pathways dont appear to change substantially in their direction or magnitude of expression between species. We further show a transcription factor, grain, that when knocked-down, induces D. prolongata leg-like phenotypes in D. melanogaster at low penetrance. Our results suggest that despite large morphological differences and patterns of dimorphism, gene expression changes between the developing tissues may be more modest than previously thought.

evolutionary biology↗

bioRxiv2023

Aberrant circuitry underlying olfaction in the face of severe olfactory bulb degeneration

The olfactory bulb (OB) is a critical component of mammalian olfactory neuroanatomy. Beyond being the first and sole relay station for olfactory information to the rest of the brain, it also contains elaborate stereotypical circuitry that is considered essential for olfaction. Indeed, substantial lesions of the OB in rodents lead to anosmia. Here, we examined the circuitry that underlies olfaction in a mouse model with severe developmental degeneration of the OB. These mice could perform odor-guided tasks and even responded normally to innate olfactory cues. Despite the near total loss of the OB, piriform cortex in these mice responded to odors normally and its neural activity sufficed to decode odor identity. We analyzed the circuitry that supports olfactory function in these mice. We found that sensory neurons express the full repertoire of olfactory receptors and their axons project primarily to the rudimentary OB, but also ectopically, to olfactory cortical regions. Within the OB, the number of principal neurons was greatly reduced and the morphology of their dendrites was abnormal, extending over larger regions within the OB. Glomerular organization was lost. This study shows that olfactory functionality can be preserved despite reduced and aberrant circuitry that is missing many of the elements that are believed to be essential for olfaction, and may explain the retention of olfaction in humans with degenerated OBs.

neuroscience↗

bioRxiv2020

Motor corollary discharge activates layer six circuits in the auditory cortex

Optogenetic activation of Ntsr1+ layer 6 corticothalamic (L6 CT) neurons modulates thalamocortical sensory processing and perception for hundreds of milliseconds following laser offset. Naturally occurring sources of extrasensory inputs that could recruit L6 CTs prior to upcoming sensory stimuli have not been identified. Here, we found that 100% of L6 CTs in mouse primary auditory cortex (A1) expressed FoxP2, a protein marker found in brain areas that coordinate sensory inputs with movement. To test the idea that motor preparatory inputs could be a natural extrasensory activator of L6 CTs, we combined quantitative videography, optogenetically targeted single unit recordings, and two-photon imaging during self-initiated behavior. We found that A1 L6 CTs were activated hundreds of milliseconds prior to orofacial movements, but not whole-body movements associated with locomotion. These findings identify new local circuit arrangements for routing motor corollary discharge into A1 and suggest new roles for CT neurons in active sensing.

neuroscience↗

bioRxiv2020

Learning-related population dynamics in the auditory thalamus

Learning to associate sensory stimuli with a chosen action has been classically attributed to the cortex. Whether the thalamus, considered mainly as an upstream area relative to cortex, encodes learning-related information is still largely unknown. We studied learning-related activity in the dorsal and medial regions of the medial geniculate body (MGB), part of the non-lemniscal auditory pathway. Using fiber photometry, we continuously imaged population calcium dynamics as mice learned a go/no-go auditory discrimination task. The MGB was tuned to frequency shortly after stimulus onset and responded to cognitive features like the choice of the mouse several hundred milliseconds later. Encoding of choice in the MGB increased with learning, and was highly correlated with the learning curves of the mice. MGB also encoded motor parameters of the mouse during the task. These results provide evidence that the MGB encodes task- motor- and learning-related information.

neuroscience↗

bioRxiv2018

The Educage: an automated platform for studying auditory perceptual learning in mice

Auditory perceptual learning of pure tones causes tonotopic map expansion in the primary auditory cortex (A1), but the function this plasticity sub-serves is unclear. We developed an automated training platform called the Educage, which was used to train mice on a go/no-go auditory discrimination task to their perceptual limits, for difficult discriminations among pure tones or natural sounds. Spiking responses of excitatory and inhibitory L2/3 neurons in mouse A1 revealed learning-induced overrepresentation of the learned frequencies, in accordance with previous literature. Using a novel computational model to study auditory tuning curves we show that overrepresentation does not necessarily improve discrimination performance of the network to the learned tones. In contrast, perceptual learning of natural sounds induced sparsening and decorrelation of the neural response, and consequently improving discrimination of these complex sounds. The signature of plasticity in A1 highlights its central role in coding natural sounds as compared to pure tones.

animal behavior and cognition↗