Biology subjects

Dorrego-Rivas, A.

Publications and source records attributed to Dorrego-Rivas, A..

3 recordsLinked to original sources

bioRxiv2026

Unilateral naris occlusion with custom-made plugs for reversible olfactory deprivation in juvenile and adult mice

Deprivation paradigms that reduce environmental input have been successfully applied across multiple species and sensory modalities, including vision, audition, somatosensation, and olfaction in order to understand how neurons and circuits respond to loss of sensory input. One notable advantage of studying sensory deprivation in the rodent olfactory system is the ease and control with which smell loss can be induced. Various methods of olfactory deprivation have long been available and rely on blocking a nostril, either through invasive and often non-reversible approaches such as chemical ablation or surgical procedures, or through reversible approaches such as unilateral naris occlusion using custom-made nose plugs. Here, we provide a systematic description of this well-established method, including its construction from commercially available materials, procedures, validation, and reliability in post-weaning mice, thereby providing a detailed and reproducible framework for controlled, reversible olfactory deprivation.

neuroscience↗

bioRxiv2026

Dishevelled2 Condensates control Axon Initial Segment (AIS) assembly and function through MTCL1-Dependent microtubule recruitment.

In the epithelium, Planar Cell Polarity (PCP) signaling coordinates cellular organization along the plane of the tissue, perpendicular to the apicobasal axis. In neurons, polarity is instead expressed through the structural and molecular asymmetry that separates the axon from the somatodendritic compartment. Core PCP proteins are essential for neuronal development and function, and have been linked to neurodevelopmental disorders, including autism spectrum disorders and epilepsy. However, their precise roles in the establishment of neuronal polarity remain incompletely understood. Here, we identify Dishevelled2 (Dvl2), a central PCP signaling scaffold, as a novel component of the axon initial segment (AIS), the proximal axonal domain that maintains neuronal polarity and initiates action potentials. We show that Dvl2 defines, both in vivo and in cultured hippocampal neurons, a proximal subdomain positioned upstream of the major AIS marker Ankyrin-G (Ank-G) and is closely associated with microtubule bundles. Dvl2 is already detected during early axon specification, suggesting that it participates in the initial organization of the proximal axon. Functional depletion of Dvl proteins disrupts AIS architecture, reduces the accumulation of Ankyrin-G and other core AIS components, and impairs the organization of AIS microtubule bundles. These structural defects translate into altered neuronal excitability, with a reduced AIS-dependent component of the action potential. Mechanistically, we identify MTCL1 as a microtubule-associated partner that recruits Dvl2 from biomolecular condensate assemblies onto microtubules. This recruitment requires the DIX and PDZ domains of Dvl2. Notably, selective intracellular binders targeting the Dvl2 PDZ domain perturb Dvl2 condensate organization and compromise AIS formation. Together, our data identify Dvl2 as an organizer of the proximal AIS and reveal a Dvl2-MTCL1-dependent mechanism coupling condensate scaffolding, microtubule organization, and neuronal excitability.

neuroscience↗

bioRxiv2024

Strikingly different neurotransmitter release strategies in dopaminergic subclasses

Neuronal function is intimately tied to axodendritic polarity. Neurotransmitter release, for example, is usually the role of the axon. There are widespread exceptions to this rule, however, including many mammalian neuronal types that can release neurotransmitter from their dendrites. In the mouse olfactory bulb, closely related subclasses of dopaminergic interneuron differ markedly in their polarity, with one subtype lacking an axon entirely. These axon-bearing and anaxonic dopaminergic subclasses have distinct developmental profiles and sensory responses, but how their fundamental polarity differences translate to functional outputs remains entirely unknown. Here, we provide anatomical evidence for distinct neurotransmitter release strategies among these closely related dopaminergic subtypes: anaxonic cells release from their dendrites, while axon-bearing neurons release exclusively from their intermittently myelinated axon. These structural differences are linked to a clear functional distinction: anaxonic, but not axon-bearing dopaminergic neurons are capable of self-inhibition. Our findings suggest that variations in polarity can produce striking distinctions in neuronal outputs, and that even closely related neuronal subclasses may play entirely separate roles in sensory information processing.

neuroscience↗