Sensory Circuits Research Articles

Integrated Bioelectronic and Optogenetic Methods to Study Brain-Body Circuits.

The peripheral nervous system, consisting of somatic sensory circuits and autonomic effector circuits, enables communication between the body's organs and the brain. Dysregulation in these circuits is implicated in an array of disorders and represents a potential target for neuromodulation therapies. In this Perspective, we discuss recent advances in the neurobiological understanding of these brain-body pathways and the expansion of neurotechnologies beyond the brain to the viscera. We focus primarily on the development of integrated technologies that leverage bioelectronic devices with optogenetic tools. We highlight the discovery and application of ultrapotent and red-shifted channelrhodopsins for minimally invasive optogenetics and as tools to study brain-body circuits. These innovations enable studies of freely behaving animals and have enhanced our understanding of the role physiological signals play in brain states and behavior.

The IgLON family of cell adhesion molecules expressed in developing neural circuits ensure the proper functioning of the sensory system in mice

Deletions and malfunctions of the IgLON family of cell adhesion molecules are associated with anatomical, behavioral, and metabolic manifestations of neuropsychiatric disorders. We have previously shown that IgLON genes are expressed in sensory nuclei/pathways and that IgLON proteins modulate sensory processing. Here, we examined the expression of IgLON alternative promoter-specific isoforms during embryonic development and studied the sensory consequences of the anatomical changes when one of the IgLON genes, Negr1, is knocked out. At the embryonal age of E12.5 and E13.5, various IgLONs were distributed differentially and dynamically in the developing sensory areas within the central and peripheral nervous system, as well as in limbs and mammary glands. Sensory tests showed that Negr1 deficiency causes differences in vestibular function and temperature sensitivity in the knockout mice. Sex-specific differences were noted across olfaction, vestibular functioning, temperature regulation, and mechanical sensitivity. Our findings highlight the involvement of IgLON molecules during sensory circuit formation and suggest Negr1’s critical role in somatosensory processing.

Pathogenic mechanisms in the evolution of food allergy.

The early development of the neonatal immune system is profoundly influenced by exposure to dietary and microbial antigens, which shapes mucosal tolerance. Successful oral tolerance induction is crucially dependent on microbially imprinted immune cells, most notably the RORγt+ regulatory T (Treg) and antigen presenting cells and is essential for preventing food allergy (FA). The development of FA can be envisioned to result from disruptions at key checkpoints (CKPTs) that govern oral tolerance induction. These include gut epithelial sensory and effector circuits that when dysregulated promote pro-allergic gut dysbiosis. They also include microbially imprinted immune regulatory circuits that are disrupted by dysbiosis and pro-allergic immune responses unleashed by the dysregulation of the aforementioned cascades. Understanding these checkpoints is essential for developing therapeutic strategies to restore immune homeostasis in FA.

Imaging Neural Activity in Intact, Semirestrained Drosophila Larvae.

The Drosophila larval nerve cord, which is the equivalent of the vertebrate spinal cord, houses the circuits required to process somatosensory stimuli (e.g., tactile, temperature, vibration, and self-movement) and generate the patterned muscle contractions underlying movement and behavior. Within this complex structure reside many cell types and cellular processes, making it difficult to experimentally access, when compared to peripheral parts of the nervous system (i.e., primary sensory neuron dendrites, motor neuron axons and synapses, and muscles). Additionally, the neurons in the larval nerve cord have small cell bodies, precluding traditional electrophysiological approaches. As such, the function of neurons in the nerve cord is less well studied than other parts of the nervous system, severely limiting our understanding of how larvae process sensory information and generate movement. Ca2+-sensitive fluorescent proteins enable the study of neuronal activity in live, genetically tractable animals, even those with small neuronal cell bodies. In addition, live imaging of neurons within the nerve cord in whole, intact animals is possible because larvae are translucent, and the use of intact animals allows for the peripheral sensory neuron circuits to remain intact. Ca2+-sensitive fluorescent proteins increase their fluorescence when voltage-gated Ca2+ channels are opened in depolarized neurons. Here, we describe an assay where a Ca2+-sensitive fluorescent protein (GCaMP6m) is expressed under the control of a GAL4 driver in a subset of neurons that reside in a circuit for vibration sensation. External vibration (sound) stimulates sensory neurons that activate the cells expressing the Ca2+-sensitive fluorescent protein. Visualization of the calcium-induced fluorescent signal with microscopy allows for quantification of neuronal activity.

Genetic engineering in oncology based on CRISPR-Cas9 technology

Purpose of the study: analysis of modern scientific data on the molecular mechanisms of the CRISPR-Cas9 system in gene editing, advantages and disadvantages in cancer research and the development of new treatment methods. Material and Methods. A comprehensive electronic search of relevant published studies was conducted in the scientific databases PubMed/MEDLINE, ScienceDirect, Wiley and Google Scholar published between 2014 and 2024. The search was tailored to the specific requirements of each database based on the following keywords: CRISPR-Cas9, sgRNA, genome editing, cancer immunotherapy, CAR-T. The search yielded 487 studies on the topic of interest, of which 54 were used to write the literature review. Additionally, the article discretely highlights the importance and challenges of CRISPR-Cas9 in the production of genetically engineered T cells for potential use in treating certain types of cancer. Results. Accordingly, CAR-T (chimeric antigen receptor T-cell) therapy is widely used as one of the main components of immunotherapy in the treatment of leukemia, lymphoma and some solid tumors. The development of programmed single guide RNAs (sgRNAs) and new modifications of the Cas9 protein has made the technology flexible and universal. CRISPR-Cas9 is often used to modify T and NK cells by designing antigen receptors to improve their sensory circuits with complex functionality capable of recognizing and killing tumor cells. At the same time, delivery of the finished ribonucleoprotein (Cas9+sgRNA) complex into the cell avoids the constitutive processes of transcription and translation, which ensures the fastest possible gene editing. Conclusion. In this review, we reviewed the scientific evidence highlighting the promising impact of CRISPR technologies in cancer research and treatment. CRISPR-Cas9 is considered a unique and effective technology in the field of genetic and biomolecular engineering.

The posterior intralaminar thalamic nucleus promotes nose-to-nose contacts leading to prosocial reception in the sequence of mouse social interaction.

Efficient social interaction is essential for an adaptive life and consists of sequential processes of multisensory events with social counterparts. Social touch/contact is a unique component that promotes a sequence of social behaviours initiated by detection and approach to assess a social stimulus and subsequent touch/contact interaction to form prosocial relationships. We hypothesized that the thalamic sensory relay circuit from the posterior intralaminar nucleus of the thalamus (pIL) to the paraventricular nucleus of the hypothalamus (PVN) and the medial amygdala (MeA) plays a key role in the social contact-mediated sequence of events. We found that neurons in the pIL along with the PVN and MeA were activated by social encounters and that pIL activity was more abundant in a direct physical encounter, whereas MeA activity was dominant in an indirect through grid encounter. Chemogenetic inhibition of pIL neurons selectively decreased the investigatory approach and sniffing of a same-sex, but not an opposite-sex, stimulus mouse in an indirect encounter situation and decreased the facial/snout contact ratio in a direct encounter setting. Furthermore, chemogenetic pIL inhibition had no impact on anxiety-like behaviours or body coordinative motor behaviours, but it impaired whisker-related and plantar touch tactile sense. We propose that the pIL circuit can relay social tactile sensations and mediate the sequence of nonsexual prosocial interactions through an investigatory approach to tactile contact and thus plays a significant role in establishing prosocial relationships in mouse models.

Maternal adverse childhood experiences and infant visual-limbic white matter development

BackgroundMaternal adverse childhood experiences (ACEs) are robust predictors of mental health for both the exposed individual and the next generation; however, the pathway through which such intergenerational risk is conferred remains unknown. The current study evaluated the association between maternal ACEs and infant brain development, including an a priori focus on circuits implicated in emotional and sensory processing. MethodsThe sample included 101 mother-infant dyads from a longitudinal study. Maternal ACEs were assessed with the Adverse Childhood Questionnaire dichotomized into low (0 or 1) and high (≥2) groups. White matter microstructure, as indexed by fractional anisotropy (FA), was assessed using structural magnetic resonance imaging in infants (41.6–46.0 weeks' postconceptional age) within a priori tracts (the cingulum, fornix, uncinate, inferior frontal occipital fasciculus, and inferior longitudinal fasciculus). Exploratory analyses were also conducted across the whole brain. ResultsHigh maternal ACEs (≥2) were associated with decreased infant left inferior longitudinal fasciculus (ILF) FA (F(1,94) = 7.78, p < .006) relative to infants of low ACE mothers. No group difference was observed within the right ILF following correction for multiple comparisons (F(1,95) = 4.29, p < .041). Follow-up analyses within the left ILF demonstrated associations between high maternal ACEs and increased left radial diffusivity (F(1,95) = 5.10, p < .006). Exploratory analyses demonstrated preliminary support for differences in visual processing networks (e.g., optic tract) as well as additional circuits less frequently examined in the context of early life adversity exposure (e.g., corticothalamic tract). ConclusionsMaternal ACEs predict neural circuit development of the inferior longitudinal fasciculus. Findings suggest that early developing sensory circuits within the infant brain are susceptible to maternal adverse childhood experiences and may have implications for the maturation of higher-order emotional and cognitive circuits.

Artificial Amacrine Retinal Circuits.

Event-based imaging represents a new paradigm in visual information processing that addresses the speed and energy efficiency shortcomings inherently present in the current complementary metal oxide semiconductor-based machine vision. Realizing such imaging systems has previously been sought using very large-scale integration technologies that have complex circuitries consisting of many photodiodes, differential amplifiers, capacitors, and resistors. Here, we demonstrate that event-driven sensing can be achieved using a simple one-resistor, one-capacitor (1R1C) circuit, where the capacitor is modified with colloidal quantum dots (CQDs) to have a photoresponse. This sensory circuit emulates the motion-tracking function of the biological retina, in which the amacrine cells in the bipolar-to-ganglion synaptic pathway produce a transient spiking signal only in response to changes in light intensity but remain inactive under constant illumination. When extended to a 2D imaging array, the individual sensors work independently and output signals only when a change in the light intensity is detected; hence, the concept of the frame in image processing is thereby removed. In this work, we present the fabrication and characterization of a CQD photocapacitor-based 1R1C circuit that has a spectral response at 1550 nm in the short-wave infrared (SWIR). We report on the key performance parameters including peak responsivity, noise, and optical noise equivalent power and discuss the operating mechanism that is responsible for spiking responses in these artificial retinal circuits. The present work sets the foundation for expanding the bioinspired vision sensor capability toward midwave infrared (MWIR) and long-wave infrared (LWIR) spectral regions that are invisible to human eyes and mainstream semiconductor technologies.

Emergent epileptiform activity in spinal sensory circuits drives ectopic bursting in afferent axons and sensory dysfunction after cord injury.

Spinal cord injury leads to hyperexcitability and dysfunction in spinal sensory processing. As hyperexcitable circuits can become epileptiform, we explored whether such activity emerges in a thoracic spinal cord injury (SCI) contusion model of neuropathic pain. Recordings from spinal sensory axons in multiple below-lesion segmental dorsal roots demonstrated that SCI facilitated the emergence of spontaneous ectopic burst spiking in afferent axons, which were correlated across multiple adjacent dorsal roots. Burst frequency correlated with behavioral mechanosensitivity. The same bursting events were recruited by afferent stimulation, and timing interactions with ongoing spontaneous bursts revealed that recruitment was limited by a prolonged post-burst refractory period. Ectopic bursting in afferent axons was driven by GABAA receptor activation, presumably by conversion of subthreshold GABAergic interneuronal presynaptic axoaxonic inhibitory actions to suprathreshold spiking. Collectively, the emergence of stereotyped bursting circuitry with hypersynchrony, sensory input activation, post-burst refractory period, and reorganization of connectivity represent defining features of an epileptiform network. Indeed, these same features were reproduced in naive animals with the convulsant 4-aminopyridine (fampridine). We conclude that spinal cord injury promotes the emergence of epileptiform activity in spinal sensory networks that promote profound corruption of sensory signaling. This includes hyperexcitability and bursting by ectopic spiking in afferent axons that propagate bidirectionally by reentrant central and peripheral projections as well as sensory circuit hypoexcitability during the burst refractory period. More broadly, the work links circuit hyperexcitability to epileptiform circuit emergence, further strengthening it as a conceptual basis to understand features of sensory dysfunction and neuropathic pain.

Sensory-motor circuit is a therapeutic target for dystonia musculorum mice, a model of hereditary sensory and autonomic neuropathy 6.

Mutations in Dystonin (DST), which encodes cytoskeletal linker proteins, cause hereditary sensory and autonomic neuropathy 6 (HSAN-VI) in humans and the dystonia musculorum (dt) phenotype in mice; however, the neuronal circuit underlying the HSAN-VI and dt phenotype is unresolved. dt mice exhibit dystonic movements accompanied by the simultaneous contraction of agonist and antagonist muscles and postnatal lethality. Here, we identified the sensory-motor circuit as a major causative neural circuit using a gene trap system that enables neural circuit-selective inactivation and restoration of Dst by Cre-mediated recombination. Sensory neuron-selective Dst deletion led to motor impairment, degeneration of proprioceptive sensory neurons, and disruption of the sensory-motor circuit. Restoration of Dst expression in sensory neurons using Cre driver mice or a single postnatal injection of Cre-expressing adeno-associated virus ameliorated sensory degeneration and improved abnormal movements. These findings demonstrate that the sensory-motor circuit is involved in the movement disorders in dt mice and that the sensory circuit is a therapeutic target for HSAN-VI.

Mitigating skeletal muscle wasting in unloading and augmenting subsequent recovery.

Skeletal muscle wasting is the hallmark pathophysiological adaptation to unloading or disuse that demonstrates the dependency on frequent mechanical stimulation (e.g. muscle activation and subsequent loading) for homeostasis of normally load-bearing muscles. In the absence of mitigation strategies, no mammalian organism is resistant to muscle atrophy driven by unloading. Given the profound impact of unloading-induced muscle wasting on physical capacity, metabolic health and immune function; mitigation strategies during unloading and/or augmentation approaches during recovery have broad healthcare implications in settings of bed-bound hospitalization, cast immobilization and spaceflight. This topical review aims to: (1) provide a succinct, state-of-the-field summary of seminal and recent findings regarding the mechanisms of unloading-induced skeletal muscle wasting; (2) discuss unsuccessful vs. promising mitigation and recovery augmentation strategies; and (3) identify knowledge gaps ripe for future research. We focus on the rapid muscle atrophy driven by relatively short-term mechanical unloading/disuse, which is in many ways mechanistically distinct from both hypermetabolic muscle wasting and denervation-induced muscle atrophy. By restricting this discussion to mechanical unloading during which all components of the nervous system remain intact (e.g. without denervation models), mechanical loading requiring motor and sensory neural circuits in muscle remain viable targets for both mitigation and recovery augmentation. We emphasize findings in humans with comparative discussions of studies in rodents which enable elaboration of key mechanisms. We also discuss what is currently known about the effects of age and sex as biological factors, and both are highlighted as knowledge gaps and novel future directions due to limited research.

Early-life maturation of the somatosensory cortex: sensory experience and beyond.

Early life experiences shape physical and behavioral outcomes throughout lifetime. Sensory circuits are especially susceptible to environmental and physiological changes during development. However, the impact of different types of early life experience are often evaluated in isolation. In this mini review, we discuss the specific effects of postnatal sensory experience, sleep, social isolation, and substance exposure on barrel cortex development. Considering these concurrent factors will improve understanding of the etiology of atypical sensory perception in many neuropsychiatric and neurodevelopmental disorders.

Support Teachers’ Awareness and Adaptability in Classroom Management Using the Sensory Circuit Program to Cope With Special Needs Student’s Behavior

This research aims to analyze and describe: (1) the awareness of the support teachers on the sensory circuit program, and (2) the adaptability of support teachers in using the sensory circuit program as a model of classroom management to cope with behavioral problems of special needs students at XYZ School South Kembangan. The research used ten indicators, fourteen questions, and five informants with an evaluation study approach. The data validity is obtained using triangulation techniques, informants’ analysis, and comparing relevant theories related and previous research. Analysis of the interview result consists of nine related quotations of awareness and twenty related quotations of adaptability showed that four out of five support teachers’ levels of awareness and adaptability are increasing. The result also found the influenced factors of the teachers’ awareness and adaptability level which included (1) consistency of hands-on practice, (2) students’ background needs, and (3) good teamwork.

A single-cell transcriptomic atlas of sensory-dependent gene expression in developing mouse visual cortex.

Sensory experience drives the refinement and maturation of neural circuits during postnatal brain development through molecular mechanisms that remain to be fully elucidated. One likely mechanism involves the sensory-dependent expression of genes that encode direct mediators of circuit remodeling within developing cells. However, while studies in adult systems have begun to uncover crucial roles for sensory-induced genes in modifying circuit connectivity, the gene programs induced by brain cells in response to sensory experience during development remain to be fully characterized. Here, we present a single-nucleus RNA-sequencing dataset describing the transcriptional responses of cells in mouse visual cortex to sensory deprivation or sensory stimulation during a developmental window when visual input is necessary for circuit refinement. We sequenced 118,529 individual nuclei across sixteen neuronal and non-neuronal cortical cell types isolated from control, sensory deprived, and sensory stimulated mice, identifying 1,268 unique sensory-induced genes within the developing brain. To demonstrate the utility of this resource, we compared the architecture and ontology of sensory-induced gene programs between cell types, annotated transcriptional induction and repression events based upon RNA velocity, and discovered Neurexin and Neuregulin signaling networks that underlie cell-cell interactions via CellChat . We find that excitatory neurons, especially layer 2/3 pyramidal neurons, are highly sensitive to sensory stimulation, and that the sensory-induced genes in these cells are poised to strengthen synapse-to-nucleus crosstalk by heightening protein serine/threonine kinase activity. Altogether, we expect this dataset to significantly broaden our understanding of the molecular mechanisms through which sensory experience shapes neural circuit wiring in the developing brain.

A Low-Power High-Sensitivity Photocurrent Sensory Circuit with Capacitive Feedback Transimpedance for Photoplethysmography Sensing.

This study presents an integrated analog front-end (AFE) tailored for photoplethysmography (PPG) sensing. The AFE module introduces a novel transimpedance amplifier (TIA) that incorporates capacitive feedback techniques alongside common drain feedback (CDF) TIA. The unique TIA topology achieves both high gain and high sensitivity while maintaining low power consumption. The resultant PPG sensor module demonstrates impressive specifications, including an input noise current of 4.81 pA/sqrt Hz, a transimpedance gain of 18.43 MΩ, and a power consumption of 68 µW. Furthermore, the sensory system integrates an LED driver featuring automatic light control (ALC), which dynamically adjusts the LED power based on the strength of the received signal. Employing 0.35 µm CMOS technology, the AFE implementation occupies a compact footprint of 1.98 mm × 2.475 mm.

Mechanosensory bristles mediate avoidance behavior by triggering sustained local motor activity in Drosophila melanogaster

During locomotion, most vertebrates-and invertebrates such as Drosophila melanogaster-are able to quickly adapt to terrain irregularities or avoid physical threats by integrating sensory information along with motor commands. Key to this adaptability are leg mechanosensory structures, which assist in motor coordination by transmitting external cues and proprioceptive information to motor centers in the central nervous system. Nevertheless, how different mechanosensory structures engage these locomotor centers remains poorly understood. Here, we tested the role of mechanosensory structures in movement initiation by optogenetically stimulating specific classes of leg sensory structures. We found that stimulation of leg mechanosensory bristles (MsBs) and the femoral chordotonal organ (ChO) is sufficient to initiate forward movement in immobile animals. While the stimulation of the ChO required brain centers to induce forward movement, unexpectedly, brief stimulation of leg MsBs triggered a fast response and sustained motor activity dependent only on the ventral nerve cord (VNC). Moreover, this leg-MsB-mediated movement lacked inter- and intra-leg coordination but preserved antagonistic muscle activity within joints. Finally, we show that leg-MsB activation mediates strong avoidance behavior away from the stimulus source, which is preserved even in the absence of a central brain. Overall, our data show that mechanosensory stimulation can elicit a fast motor response, independently of central brain commands, to evade potentially harmful stimuli. In addition, it sheds light on how specific sensory circuits modulate motor control, including initiation of movement, allowing a better understanding of how different levels of coordination are controlled by the VNC and central brain locomotor circuits.

Hide-and-sick: How bacteria manipulate a neural circuit that makes you sick

Hide-and-sick: How bacteria manipulate a neural circuit that makes you sick

Memorability shapes perceived time (and vice versa).

Visual stimuli are known to vary in their perceived duration. Some visual stimuli are also known to linger for longer in memory. Yet, whether these two features of visual processing are linked is unknown. Despite early assumptions that time is an extracted or higher-order feature of perception, more recent work over the past two decades has demonstrated that timing may be instantiated within sensory modality circuits. A primary location for many of these studies is the visual system, where duration-sensitive responses have been demonstrated. Furthermore, visual stimulus features have been observed to shift perceived duration. These findings suggest that visual circuits mediate or construct perceived time. Here we present evidence across a series of experiments that perceived time is affected by the image properties of scene size, clutter and memorability. More specifically, we observe that scene size and memorability dilate time, whereas clutter contracts it. Furthermore, the durations of more memorable images are also perceived more precisely. Conversely, the longer the perceived duration of an image, the more memorable it is. To explain these findings, we applied a recurrent convolutional neural network model of the ventral visual system, in which images are progressively processed over time. We find that more memorable images are processed faster, and that this increase in processing speed predicts both the lengthening and the increased precision of perceived durations. These findings provide evidence for a link between image features, time perception and memory that can be further explored with models of visual processing.

A primary sensory cortical interareal feedforward inhibitory circuit for tacto-visual integration

Tactile sensation and vision are often both utilized for the exploration of objects that are within reach though it is not known whether or how these two distinct sensory systems combine such information. Here in mice, we used a combination of stereo photogrammetry for 3D reconstruction of the whisker array, brain-wide anatomical tracing and functional connectivity analysis to explore the possibility of tacto-visual convergence in sensory space and within the circuitry of the primary visual cortex (VISp). Strikingly, we find that stimulation of the contralateral whisker array suppresses visually evoked activity in a tacto-visual sub-region of VISp whose visual space representation closely overlaps with the whisker search space. This suppression is mediated by local fast-spiking interneurons that receive a direct cortico-cortical input predominantly from layer 6 neurons located in the posterior primary somatosensory barrel cortex (SSp-bfd). These data demonstrate functional convergence within and between two primary sensory cortical areas for multisensory object detection and recognition.

Female-specific dysfunction of sensory neocortical circuits in a mouse model of autism mediated by mGluR5 and estrogen receptor α

Little is known of the brain mechanisms that mediate sex-specific autism symptoms. Here, we demonstrate that deletion of the autism spectrum disorder (ASD)-risk gene, Pten, in neocortical pyramidal neurons (NSEPten knockout [KO]) results in robust cortical circuit hyperexcitability selectively in female mice observed as prolonged spontaneous persistent activity states. Circuit hyperexcitability in females is mediated by metabotropic glutamate receptor 5 (mGluR5) and estrogen receptor α (ERα) signaling to mitogen-activated protein kinases (Erk1/2) and de novo protein synthesis. Pten KO layer 5 neurons have a female-specific increase in mGluR5 and mGluR5-dependent protein synthesis. Furthermore, mGluR5-ERα complexes are generally elevated in female cortices, and genetic reduction of ERα rescues enhanced circuit excitability, protein synthesis, and neuron size selectively in NSEPten KO females. Female NSEPten KO mice display deficits in sensory processing and social behaviors as well as mGluR5-dependent seizures. These results reveal mechanisms by which sex and a high-confidence ASD-risk gene interact to affect brain function and behavior.