Biology subjects

Gomez-Ramirez, M.

Publications and source records attributed to Gomez-Ramirez, M..

8 recordsLinked to original sources

bioRxiv2025

Spatial flexibility of distractor suppression in the tactile modality

Object sensing and manipulation rely on the somatosensory systems ability to relay relevant information about a skin location encoding tactile information about the object while suppressing irrelevant or distracting inputs on the skin--a process known as distractor suppression. Although tactile selective attention is flexible, capable of being allocated to non-contiguous skin areas on the hand and with spatial resolution limited to within a finger, the spatial properties of distractor suppression in touch remain poorly understood. In particular, studies have not explored the effects of proactively cueing distractor locations in touch, leaving open questions about whether active deployment of distractor suppression operates independently of attentional enhancement. To address this gap in knowledge, in this study, participants performed an amplitude discrimination task on the hand in the presence of distractors that were cued in advance. Our data revealed that validly cueing distractor locations improves discrimination accuracy and reduces reaction times of behaviorally-relevant tactile stimuli. The data also showed that behavior is unaffected when attended stimuli are flanked by distractors within or across fingers, suggesting that distractor suppression mechanisms can be split across different skin locations on the hand. These findings provide novel insights into the spatial allocation and flexibility of distractor suppression mechanisms in touch, and underscore the importance of proactive cueing in shaping these mechanisms.

neuroscience↗

bioRxiv2024

Strength of Activation and Temporal Dynamics of BioLuminescent-Optogenetics in Response to Systemic Injections of the Luciferin

BioLuminescent OptoGenetics ("BL-OG") is a chemogenetic method that can evoke optogenetic reactions in the brain non-invasively. In BL-OG, an enzyme that catalyzes a light producing reaction (i.e., a luciferase) is tethered to an optogenetic element that is activated in response to bioluminescent light. Bioluminescence is generated by injecting a chemical substrate (luciferin, e.g., h-Coelenterazine; h-CTZ) that is catalyzed by the luciferase. By directly injecting the luciferin into the brain, we showed that bioluminescent light is proportional to spiking activity, and this relationship scales as a function of luciferin dosage. Here, we build on these previous observations by characterizing the temporal dynamics and dose response curves of BL-OG effects to intravenous (IV) injections of the luciferin. We imaged bioluminescence through a thinned skull of mice running on a wheel, while delivering h-CTZ via the tail vein with different dosage concentrations and injection rates. The data reveal a systematic relationship between strength of bioluminescence and h-CTZ dosage, with higher concentration generating stronger bioluminescence. We also found that bioluminescent activity occurs rapidly (< 60 seconds after IV injection) regardless of concentration dosage. However, as expected, the onset time of bioluminescence is delayed as the injection rate decreases. Notably, the strength and time decay of bioluminescence is invariant to the injection rate of h-CTZ. Taken together, these data show that BL-OG effects are highly consistent across injection parameters of h-CTZ, highlighting the reliability of BL-OG as a non-invasive neuromodulation method.

neuroscience↗

bioRxiv2023

Towards a Brighter Constellation: Multi-Organ Neuroimaging of Neural and Vascular Dynamics in the Spinal Cord and Brain

SignificancePain is comprised of a complex interaction between motor action and somatosensation that is dependent on dynamic interactions between the brain and spinal cord. This makes understanding pain particularly challenging as it involves rich interactions between many circuits (e.g., neural and vascular) and signaling cascades throughout the body. As such, experimentation on a single region may lead to an incomplete and potentially incorrect understanding of crucial underlying mechanisms. AimHere, we aimed to develop and validate new tools to enable detailed and extended observation of neural and vascular activity in the brain and spinal cord. The first key set of innovations were targeted to developing novel imaging hardware that addresses the many challenges of multi-site imaging. The second key set of innovations were targeted to enabling bioluminescent imaging, as this approach can address limitations of fluorescent microscopy including photobleaching, phototoxicity and decreased resolution due to scattering of excitation signals. ApproachWe designed 3D-printed brain and spinal cord implants to enable effective surgical implantations and optical access with wearable miniscopes or an open window (e.g., for one-or two-photon microscopy or optogenetic stimulation). We also tested the viability for bioluminescent imaging, and developed a novel modified miniscope optimized for these signals (BLmini). ResultsHere, we describe novel universal implants for acute and chronic simultaneous brain-spinal cord imaging and optical stimulation. We further describe successful imaging of bioluminescent signals in both foci, and a new miniscope, the BLmini, which has reduced weight, cost and form-factor relative to standard wearable miniscopes. ConclusionsThe combination of 3D printed implants, advanced imaging tools, and bioluminescence imaging techniques offers a new coalition of methods for understanding spinal cord-brain interactions. This work has the potential for use in future research into neuropathic pain and other sensory disorders and motor behavior.

bioengineering↗

bioRxiv2023

Flexible Perception of Tactile Motion in Multiple Reference Frames

AO_SCPLOWBSTRACTC_SCPLOWLeading models of somatosensory processing posit that integration of tactile and proprioceptive cues is essential for touch perception. Yet, such integration is not universally beneficial. While posture-dependent remapping of tactile signals is critical for guiding hand actions, discrimination of certain tactile features is enhanced when touch is represented independently of hand posture. How the brain flexibly controls the integration of tactile and proprioceptive cues based on task demands remains unclear, as most studies have only examined touch perception within a single reference frame. Here, we studied how reference frame demands shape touch perception in humans making motion judgements on a finger, while varying hand posture. Participants were cued to report motion direction relative to the finger or the sternum (i.e., the bodys midline). We found that tactile and proprioceptive cues are integrated in a task-specific manner, with hand posture biasing judgments only in the Sternum-centric task. Further, we observe that reaction times are faster for Sternum-centric judgments, with accumulation-to-bound models indicating that this advantage is driven by lower decision thresholds. Finally, we developed a Bayesian computational framework that formalizes how tactile motion signals are transformed across hand postures, advancing our understanding of how the brain maps sensory information from skin-to body-centered coordinates. Together, these findings demonstrate that reference frame task demands shape both the transformation of tactile information and speed of perceptual decisions, within a Bayesian computational framework for task-dependent coordinate transformations.

neuroscience↗

bioRxiv2023

A Bioluminescent Activity Dependent (BLADe) Platform for Converting Neuronal Activity to Photoreceptor Activation

Genetically encoded sensors and actuators have advanced the ability to observe and manipulate cellular activity, yet few non-invasive strategies enable cells to directly couple their intracellular states to user-defined outputs. We promote a bioluminescent activity-dependent (BLADe) platform that facilitates programmable feedback through genetically encoded light generation. Using calcium (Ca{superscript 2}) flux as a model, we engineered a Ca{superscript 2}-dependent luciferase that functions as an activity-gated light source capable of photoactivating light-sensing actuators. As an initial demonstration of the versatility of this platform we present two separate use cases in neurons. In the first application, the presence of luciferin triggers Ca{superscript 2} dependent local illumination that provides activity dependent gene expression by activating a light-sensitive transcription factor. In the second application, neuronal activity-driven Ca{superscript 2} fluctuations via locally generated bioluminescence control neural dynamics through opsin activation in single cells, populations and intact tissue. BLADe can be expanded to couple any signal that bioluminescent enzymes can be engineered to detect with the wide variety of photosensing actuators. This modular strategy of coupling an activity dependent light emitter to a light sensing actuator offers, in principle, a generalizable framework for state dependent cell-autonomous control across biological systems.

neuroscience↗

bioRxiv2022

Multi-finger Receptive Field Properties in Primary Somatosensory Cortex: A Revised Account of the Spatio-Temporal Integration Functions of Area 3b

AO_SCPLOWBSTRACTC_SCPLOWThe leading view in the somatosensory system indicates that area 3b serves as a cortical relay site that encodes cutaneous (tactile) features limited to individual digits. Our recent work argues against this model by showing that cells in area 3b integrate information from cutaneous and proprioceptive modalities. Here, we further test this model, by studying the multi-finger neural integration properties of area 3b. In contrast to the prevailing view, we found that most cells in area 3b have a receptive field (RF) that extends to multiple digits. Responses to tactile stimulation emerged earlier in cells with a multi-digit (MD) vs. single-digit (SD) RF. We also found that the RF size of MD cells (the number of responsive digits) increased across time, and the orientation preference across digits was highly correlated. Taken together, these data provide strong evidence that area 3b plays a larger role in generating neural representations of tactile objects, as opposed to just being a feature detector relay site.

neuroscience↗

bioRxiv2020

Miniaturized Devices for Bioluminescence Imaging in Freely Behaving Animals

Fluorescence miniature microscopy in vivo has recently proven a major advance, enabling cellular imaging in freely behaving animals. However, fluorescence imaging suffers from autofluorescence, phototoxicity, photobleaching and non-homogeneous illumination artifacts. These factors limit the quality and time course of data collection. Bioluminescence provides an alternative kind of activity-dependent light indicator. Bioluminescent calcium indicators do not require light input, instead generating photons through chemiluminescence. As such, limitations inherent to the requirement for light presentation are eliminated. Further, bioluminescent indicators also do not require excitation light optics: the removal of this component should make lighter and lower cost microscope with fewer assembly parts. While there has been significant recent progress in making brighter and faster bioluminescence indicators, parallel advances in imaging hardware have not yet been realized. A hardware challenge is that despite potentially higher signal-to-noise of bioluminescence, the signal strength is lower than that of fluorescence. An open question we address in this report is whether fluorescent miniature microscopes can be rendered sensitive enough to detect bioluminescence. We demonstrate this possibility in vitro and in vivo by implementing optimizations of the UCLA fluorescent miniscope. These optimizations yielded a miniscope (BLmini) which is 22% lighter in weight, has 45% fewer components, is up to 58% less expensive, offers up to 15 times stronger signal (as dichroic filtering is not required) and is sensitive enough to capture spatiotemporal dynamics of bioluminescence in the brain with a signal-to-noise ratio of 34 dB.

bioengineering↗

bioRxiv2019

The BioLuminescent-OptoGenetic in vivo Response to Coelenterazine is Proportional, Sensitive and Specific in Neocortex

BioLuminescent (BL) light production can modulate neural activity and behavior through coexpressed OptoGenetic (OG) elements, an approach termed BL-OG. Yet, the relationship between BL-OG effects and bioluminescent photon emission has not been characterized in vivo. Further, the degree to which BL-OG effects strictly depend on optogenetic mechanisms driven by bioluminescent photons is unknown. Crucial to every neuromodulation method is whether the activator shows a dynamic concentration range driving robust, selective, and non-toxic effects. We systematically tested the effects of four key components of the BL-OG mechanism (luciferin, oxidized luciferin, luciferin vehicle, and bioluminescence), and compared these against effects induced by the Luminopsin-3 (LMO3) BL-OG molecule, a fusion of slow burn Gaussia luciferase (sbGLuc) and Volvox ChannelRhodopsin-1 (VChR1). We performed combined bioluminescence imaging and electrophysiological recordings while injecting specific doses of Coelenterazine (substrate for sbGluc), Coelenteramide (CTM, the oxidized product of CTZ), or CTZ vehicle. CTZ robustly drove activity in mice expressing LMO3, with photon production proportional to firing rate. In contrast, low and moderate doses of CTZ, CTM, or vehicle did not modulate activity in mice that did not express LMO3. We also failed to find bioluminescence effects on neural activity in mice expressing an optogenetically non-sensitive LMO3 variant. We observed weak responses to the highest dose of CTZ in control mice, but these effects were significantly smaller than those observed in the LMO3 group. These results show that in neocortex in vivo, there is a large CTZ range wherein BL-OG effects are specific to its active chemogenetic mechanism.

neuroscience↗