Biology subjects

Paricio-Montesinos, R.

Publications and source records attributed to Paricio-Montesinos, R..

5 recordsLinked to original sources

bioRxiv2026

A thalamic inhibitory circuit aligns sensory coding with learned value

Adaptive behavior requires sensory systems to prioritize cues that predict meaningful outcomes while suppressing irrelevant stimuli, but how relevance-based filtering is implemented along early sensory pathways remains unclear. Using deep brain two-photon imaging and causal circuit manipulations in mice performing an audiovisual detection task, we show that inhibition from thalamic reticular nucleus dynamically tunes sensory thalamus according to learned value. As animals learned stimulus-outcome associations, neurons in medial geniculate body developed biased responses favoring reward-predicting cues and suppressing non-rewarded stimuli. Silencing inhibitory input from thalamic reticular nucleus broadly disinhibited thalamic responses and abolished this value bias. Notably, stimulus identity decoding was unaffected by loss of inhibition. However, the geometry of MGB population activity was reorganized: coding axes rotated, action-related coding was strongly impaired, and thalamic representations became misaligned with learned behavioral readout. This altered population code impaired behavioral performance despite preserved sensory separability. Thus, inhibition of sensory thalamus by the reticular nucleus does not simply gate sensory throughput; it acts as a subcortical coding mechanism that aligns neuronal representations with learned value and behavioral goals, with implications for disorders of perception and cognition.

neuroscience↗

bioRxiv2023

Cortical cellular encoding of thermotactile integration

Recent evidence suggests that primary sensory cortical regions play a role in the integration of information from multiple sensory modalities. How primary cortical neurons integrate multisensory information is unclear, partly because multisensory interactions in the cortex are typically weak or modulatory. To address this question, we take advantage of the robust representation of thermal (cooling) and tactile stimuli in mouse forepaw primary somatosensory cortex (fS1). Using a thermotactile detection task, we show that the perception of threshold level cool or tactile information is enhanced when they are presented simultaneously compared to presentation alone. To investigate the cortical correlates of thermotactile integration, we performed in vivo extracellular recordings from fS1 during unimodal and bimodal stimulation of the forepaw. Unimodal stimulation evoked thermal- or tactile- specific excitatory and inhibitory responses of fS1 neurons. The most prominent features of bimodal, thermotactile stimulation are the recruitment of unimodally silent fS1 neurons, non-linear integration features and a change in the response dynamics to favor longer response durations. Together, we identify quantitative and qualitative changes in cortical encoding that may underlie the improvement in perception of multisensory, thermotactile surfaces during haptic exploration.

neuroscience↗

bioRxiv2022

Sensory Schwann cells are required for mechanical nociception and touch perception

That sensory neurons alone transduce mechanical stimuli was challenged by the discovery of nociceptive Schwann cells that can initiate pain. Consistent with the existence of inherently mechanosensitive sensory Schwann cells, we found that the mechanosensory function of almost all nociceptors, including those signaling fast pain, were critically dependent on sensory Schwann cells. Furthermore, in polymodal nociceptors, sensory Schwann cells signal mechanical, but not cold or heat pain. Terminal Schwann cells also surround mechanoreceptor nerve-endings within the Meissners corpuscle and in at hair follicle lanceolate endings that both signal vibrotactile touch. Within Meissners corpuscles, two molecularly and functionally distinct sensory Schwann cells positive for Sox10 and Sox2 differentially modulate rapidly adapting mechanoreceptor function. Using optogenetics we show that Meissners corpuscle Schwann cells are necessary for the perception of low threshold vibrotactile stimuli. These results show that sensory Schwann cells within diverse glio-neural mechanosensory end-organs are sensors for mechanical pain as well as necessary for touch perception. Thus, specialized sensory Schwann are central to the transduction of mechanical forces that underpin somatic sensation.

neuroscience↗

bioRxiv2020

USH2A is a Meissner corpuscle end-organ protein necessary for vibration sensing in mice and humans

Fingertip mechanoreceptors comprise sensory neuron endings together with specialized skin cells that form the end-organ. Exquisitely sensitive vibration-sensing neurons are associated with Meissners corpuscles and Pacinian corpuscles1. Such end-organ structures have been recognized for more than 160 years, but their exact functions have remained a matter of speculation. Here we examined the role of USH2A in touch sensation in humans and mice. The USH2A gene encodes a transmembrane protein with a very large extracellular domain. Pathogenic USH2A mutations cause Usher syndrome associated with hearing loss and visual impairment2. We show that patients with biallelic pathogenic USH2A mutations also have profound impairments in vibrotactile touch perception. Similarly, mice lacking the USH2A protein showed severe deficits in a forepaw vibrotactile discrimination task. Forepaw rapidly-adapting mechanoreceptors (RAMs) recorded from Ush2a-/- mice innervating Meissners corpuscles showed profound reductions in their vibration sensitivity. However, the USH2A protein was not expressed in sensory neurons, but was found in specialized terminal Schwann cells in Meissners corpuscles. Loss of this large extracellular tether-like protein in corpuscular end-organs innervated by RAMs was sufficient to reduce the vibration sensitivity of mechanoreceptors. Thus, USH2A expressed in corpuscular end-organs associated with vibration sensing is required to properly perceive vibration. We propose that cells within the corpuscle present a tether-like protein that may link to mechanosensitive channels in sensory endings to facilitate small amplitude vibration detection essential for the perception of fine textured surfaces.

neuroscience↗

bioRxiv2018

The sensory coding of warm perception

Humans easily discriminate tiny skin temperature changes that are perceived as warming or cooling. Dedicated thermoreceptors forming distinct thermosensory channels or \"labelled lines\" are thought to underlie thermal perception. We show that mice have similar perceptual thresholds for forepaw warming to humans (~1 {degrees}C change) and do not mistake warming for cooling. Mice perform warm discrimination tasks without dedicated thermoreceptors, but use information carried by unmyelinated polymodal C-fibers. Deletion of the heat-sensitive transduction channels TRPM2 and TRPV1 did not impact warming perception or afferent coding of warm. However, without the cold sensitive TRPM8 channel, afferent coding of cooling was impaired and these mice cannot perceive warming or cooling. Our data is incompatible with the existence of thermospecific labelled lines, but can be reconciled by the existence of central circuits that compare and integrate the input from at least two types of polymodal afferents, hitherto thought to exclusively signal pain.

neuroscience↗