Biology subjects

Bozza, T.

Publications and source records attributed to Bozza, T..

6 recordsLinked to original sources

bioRxiv2025

A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain

Although topographical maps organize many peripheral sensory systems, it remains unclear whether olfactory sensory neurons (OSNs) choose which of the [~]1100 odor receptors (ORs) to express based upon their spatial location in the olfactory epithelium (OE) or instead ORs are scattered randomly. Here we reveal that each OR is expressed at a precise mean position along the OE dorsoventral axis, thereby instantiating a receptor map. This patterning reflects the differential use, by precursors and mature OSNs, of a coherent gene expression program controlled by a spatially-varying retinoic acid gradient; this program -- which includes key transcription factors and axon guidance genes -- translates position into a spatially appropriate distribution of OR choices and aligns the epithelial map of OR identity with the glomerular map present in the olfactory bulb. These results identify a transcriptional code that distinguishes and spatially organizes the vast array of sensory channels that comprise the olfactory system.

neuroscience↗

bioRxiv2024

Flp-recombinase mouse line for genetic manipulation of ipRGCs

Light has myriad impacts on behavior, health, and physiology. These signals originate in the retina and are relayed to the brain by more than 40 types of retinal ganglion cells (RGCs). Despite a growing appreciation for the diversity of RGCs, how these diverse channels of light information are ultimately integrated by the [~]50 retinorecipient brain targets to drive these light-evoked effects is a major open question. This gap in understanding primarily stems from a lack of genetic tools that specifically label, manipulate, or ablate specific RGC types. Here, we report the generation and characterization of a new mouse line (Opn4FlpO), in which FlpO is expressed from the Opn4 locus, to manipulate the melanopsin-expressing, intrinsically photosensitive retinal ganglion cells. We find that the Opn4FlpO line, when crossed to multiple reporters, drives expression that is confined to ipRGCs and primarily labels the M1-M3 subtypes. Labeled cells in this mouse line show the expected intrinsic, melanopsin-based light response and morphological features consistent with the M1-M3 subtypes. In alignment with the morphological and physiological findings, we see strong innervation of non-image forming brain targets by ipRGC axons, and weaker innervation of image forming targets in Opn4FlpO mice labeled using AAV-based and FlpO-reporter lines. Consistent with the FlpO insertion disrupting the endogenous Opn4 transcript, we find that Opn4FlpO/FlpO mice show deficits in the pupillary light reflex, demonstrating their utility for behavioral research in future experiments. Overall, the Opn4FlpO mouse line drives Flp-recombinase expression that is confined to ipRGCs and most effectively drives recombination in M1-M3 ipRGCs. This mouse line will be of broad use to those interested in manipulating ipRGCs through a Flp-based recombinase for intersectional studies or in combination with other, non-Opn4 Cre driver lines.

neuroscience↗

bioRxiv2021

Map-independent representation of an aggression-promoting social cue in the main olfactory pathway

AO_SCPLOWBSTRACTC_SCPLOWWhile the olfactory system is required for proper social behaviors, the molecular basis for how social cues are detected via the main olfactory pathway of mammals is not well-characterized. Trimethylamine is a volatile, sex-specific odor found in adult male mouse urine that selectively activates main olfactory sensory neurons that express trace amine-associated receptor 5 (TAAR5). Here we show that trimethylamine, acting via TAAR5, elicits state-dependent attraction or aversion in male mice and drives inter-male aggression. Genetic knockout of TAAR5 significantly reduces aggression-related behaviors, while adding trimethylamine augments aggressive behavior towards juvenile males. We further show that transgenic expression of TAAR5 specifically in olfactory sensory neurons rescues aggressive behaviors in knockout mice, despite extensive remapping of TAAR5 projections to the olfactory bulb. Our results identify a specific main olfactory input that detects a prominent male-specific odor to induce inter-male aggression in a mammalian species and reveal that apparently innate behavioral responses are independent of patterned glomerular input to the olfactory bulb.

neuroscience↗

bioRxiv2020

A mouse bio-electronic nose for sensitive and versatile chemical detection

When it comes to simultaneous versatility, speed, and specificity in detecting volatile chemicals, biological olfactory systems far outperform all artificial chemical detection devices. Consequently, the use of trained animals for chemical detection in security, defense, healthcare, agriculture, and other applications has grown astronomically. However, the use of animals in this capacity requires extensive training and behavior-based communication. Here we propose an alternative strategy, a bio-electronic nose, that capitalizes on the superior capability of the mammalian olfactory system, but bypasses behavioral output by reading olfactory information directly from the brain. We engineered a brain-machine interface that captures neuronal signals from an early stage of olfactory processing in awake mice, and used machine learning techniques to form a sensitive and selective chemical detector. We chronically implanted a grid electrode array on the surface of the mouse olfactory bulb and systematically recorded responses to a large battery of odorants and odorant mixtures across a wide range of concentrations. The bio-electronic nose has a comparable sensitivity to the trained animal and can detect odors on a variable background. We also introduce a novel genetic engineering approach designed to improve the sensitivity of our bio-electronic nose for specific chemical targets. Our bio-electronic nose outperforms current detection methods and unlocks a wide spectrum of civil, medical and environmental applications.

bioengineering↗

bioRxiv2018

Single olfactory receptors set odor detection thresholds

In many species, survival depends on olfaction, yet the mechanisms that underlie olfactory sensitivity are not well understood. Here, we examine how a conserved subset of olfactory receptors, the trace amine-associated receptors (TAARs) determine odor detection thresholds of mice to amines. We find that deleting all TAARs, or even single TAARs, results in significant odor detection deficits. This finding is not limited to TAARs, as the deletion of a canonical odorant receptor reduced behavioral sensitivity to its preferred ligand. Remarkably, behavioral threshold is set solely by the most sensitive receptor, with no contribution from other highly sensitive receptors. In addition, increasing the number of sensory neurons (and glomeruli) expressing a threshold-determining TAAR does not improve detection, indicating that sensitivity is not limited by the typical complement of sensory neurons. Our findings demonstrate that olfactory thresholds are set by the single highest affinity receptor, and suggest that TAARs are evolutionarily conserved because they determine the sensitivity to a class of biologically relevant chemicals.

neuroscience↗

bioRxiv2017

Stimulus Dependent Diversity And Stereotypy In The Output Of An Olfactory Functional Unit

Olfactory inputs are organized in an array of parallel functional units (glomeruli), each relaying information from sensory neurons that express a given odorant receptor to a small population of output neurons, mitral/tufted (MT) cells. MT cells have complex temporal responses to odorants, but how these diverse responses relate to stimulus features is not known. We recorded in awake mice responses from \"sister\" MT cells that receive input from a functionally-characterized, genetically identified glomerulus, corresponding to a specific receptor (M72). Despite receiving similar inputs, sister MT cells exhibited temporally diverse, concentration variant, excitatory and inhibitory responses to most M72 ligands. In contrast, the strongest known ligand for M72 elicited temporally-stereotyped, early excitatory responses in all sister MT cells that persisted across all odor concentrations. Our data demonstrate that information about ligand affinity is encoded in the collective stereotypy or diversity of activity among sister MT cells within a glomerular functional unit in concentration-independent manner.

neuroscience↗