Biology subjects

Mazo, C.

Publications and source records attributed to Mazo, C..

6 recordsLinked to original sources

bioRxiv2026

Direct cortical feedforward and feedback pathways differentially shape visual responses and selectively engage looped circuits

Nearly every computational account of hierarchical cortex rests on assumptions about the influence of direct cortico-cortical inputs and which neurons they act upon. Yet, disentangling their direct functional contributions from indirect, multisynaptic influences remains difficult. We examined how feedforward (FF) and feedback (FB) pathways between mouse primary visual cortex (V1) and posteromedial cortex (PM) modulate visual responses, combining retrograde labelling, multi-area two-photon imaging and optogenetic perturbations. High or low activity in either pathway was associated with both excitation and inhibition of neurons in the targeted areas. FF activity was associated with stronger additive changes, while FB activity was related to stronger multiplicative modulations and improvements in visual decoding. Optogenetic manipulations causally confirmed these asymmetries. Both pathways preferentially modulated reciprocating "looped" neurons, with FF exciting them and FB either exciting or inhibiting them. These findings demonstrate that feedforward and feedback pathways serve distinct functional roles within recurrent cortical loops.

neuroscience↗

bioRxiv2025

Wound healing and angiogenic profiling of dermal endothelial cells isolated from people with type 2 diabetes.

Impaired wound healing in type 2 diabetes (T2D) is associated with microvascular dysfunction and remains a significant clinical challenge. We aimed to determine whether primary human dermal microvascular endothelial cells (HDMVECs) from individuals with T2D exhibit abnormal cellular functions, and whether exposure to T2D serum impacts healthy endothelial function. In Experiment 1, T2D-HDMVECs displayed paradoxically higher migratory and angiogenic capacities than their healthy counterparts, despite markedly reduced eNOS expression and disrupted endothelial-identity gene expression. In Experiments 2 and 3, healthy HDMVECs showed decreased tube formation, nitric oxide production, and Notch/angiogenesis-related gene expression after exposure to both healthy and T2D serum, suggesting the presence of serum-derived factors that inhibit these pathways. However, T2D-HDMVECs remained largely unresponsive to these serum-driven effects, reinforcing an "intrinsic" reprogramming of T2D endothelial cells. Overall, our data reveal a complex interplay between cell-autonomous alterations and extrinsic signals in diabetic endothelial dysfunction. Therapeutic strategies targeting both intrinsic cellular programs (e.g., eNOS, Notch signaling) and the circulating milieu may represent promising avenues for enhancing wound repair in patients with T2D.

physiology↗

bioRxiv2025

Distinct roles of cortical layer 5 subtypes in associative learning

Adaptive behavior is critically dependent on associative learning, where environmental cues are linked with subsequent positive or negative outcomes. In mammals, primary neocortical sensory areas serve as pivotal nodes in this process, processing stimuli and distributing information to cortical and subcortical networks. Layer 5 (L5) of the cortex comprises two types of pyramidal projection neurons--intratelencephalic (IT) and extratelencephalic (ET) neurons--each with distinct downstream targets. Despite the crucial function of L5 as a main output node of the cortex, the specific contributions of these L5 neuronal subtypes to associative learning remain poorly understood. In the present study, by leveraging transgenic mouse lines, we distinguished IT and ET neurons in the primary somatosensory cortex and examined their roles in a whisker-based frequency-discrimination learning task. Longitudinal two-photon calcium imaging revealed distinct response characteristics between IT and ET neurons throughout learning. Interestingly, the activity of IT neurons hardly changed over the five days of learning, while the activity of ET neurons developed robustly. Furthermore, IT neurons appeared to show stimuli encoding from the beginning, whereas the ET neurons became increasingly responsive to stimuli associated with reward. Chemogenetic silencing of either IT or ET neurons both impaired learning, but in strikingly distinct ways, each associated with a different phase of learning. By modeling the response characteristics of IT and ET neurons using a reinforcement learning framework, we show that IT neurons primarily encode sensory stimuli, and their representations are critical for forming stimulus-reward associations. ET neurons instead represent the value of the stimulus, used for refining behavior. Thus, our results delineate the distinct roles of L5 IT and ET neurons, underscoring their integral and complementary contributions to associative learning.

neuroscience↗

bioRxiv2023

Auditory cortex conveys non-topographic sound localization signals to visual cortex.

Perception requires binding spatiotemporally congruent multimodal sensory stimuli. The auditory cortex (AC) sends projections to the primary visual cortex (V1), which could provide signals for binding spatially corresponding audio-visual stimuli. However, it is unknown whether AC inputs in V1 encode sound location. We used dual-color two-photon axonal calcium imaging and an array of speakers to measure the auditory spatial information that AC transmits to V1. We found that AC relays information about the location of ipsilateral and contralateral sound sources to V1. Sound location could be accurately decoded by sampling AC axons in V1, providing a substrate for making location-specific audiovisual associations. However, AC inputs were not retinotopically arranged in V1, and audio-visual modulations of V1 neurons did not depend on the spatial congruency of the sound and light stimuli. The distributed, non-topographic sound localization signals provided by AC might allow the association of specific audiovisual spatial patterns in V1 neurons.

neuroscience↗

bioRxiv2020

Long-range GABAergic projections contribute to cortical feedback control of sensory processing.

Cortical sensory areas send excitatory projections back to earlier stage of sensory processing. Here, we uncover for the first time the existence of a corticofugal inhibitory feedback between two sensory areas, paralleling the well-documented excitatory feedback. In the olfactory system, we reveal that a subpopulation of GABAergic neurons in the anterior olfactory nucleus and anterior piriform cortex target the olfactory bulb. These long-range inhibitory inputs synapse with both local and output olfactory bulb neurons, mitral and tufted cells. Optogenetic stimulation coupled to in vivo imaging and network modeling showed that activation these inhibitory inputs drives a net subtractive inhibition of both spontaneous and odor-evoked activity in local as well as mitral and tufted cells. Further, cortical GABAergic feedback stimulation enhanced separation of population odor responses in tufted cells, but not mitral cells. Targeted pharmacogenetic silencing of cortical GABAergic axon terminals in the OB impaired discrimination of similar odor mixtures. We propose here that cortical GABAergic feedback represents a new circuit motif in sensory systems, involved in refining sensory processing and perception.

neuroscience↗

bioRxiv2017

Distinct projection patterns of different classes of layer 2 principal neurons in the olfactorycortex

Processing of olfactory information in the anterior piriform cortex (APC) is widely thought to be non-topographic due to distributed projections from the olfactory bulb (OB). Layer 2 principal neurons in the APC can be divided into 2 subtypes: semilunar (SL) and superficial pyramidal (SP) cells. Although it is known that SL and SP cells receive differential inputs from the OB, little is known about their projection pattern to downstream structures, such as the posterior piriform cortex (PPC). Here we examined feedforward and feedback axonal projections of SL and SP cells using a combination of mouse genetics, and retrograde labeling. Retrograde tracing from the OB or PPC showed that the APC projects to these higher and lower brain regions mainly through layer 2b cells, while dual-labeling revealed a sizeable fraction of cells extending collaterals to both target regions. Furthermore, a transgenic mouse line specifically labeling SL cells showed that they send profuse axonal projections to olfactory cortical areas, but not to the OB. These findings support a model in which information flow from SL to SP cells and back to the OB forms a hierarchical feedback circuit whereas the two cell types process recurrent and feedforward information in a parallel manner.

neuroscience↗