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Journal of Neurophysiology Jun 2021As the tools to simultaneously record electrophysiological signals from large numbers of neurons within and across brain regions become increasingly available, this...
As the tools to simultaneously record electrophysiological signals from large numbers of neurons within and across brain regions become increasingly available, this opens up for the first time the possibility of establishing the details of causal relationships between monosynaptically connected neurons and the patterns of neural activation that underlie perception and behavior. Although recorded activity across synaptically connected neurons has served as the cornerstone for much of what we know about synaptic transmission and plasticity, this has largely been relegated to ex vivo preparations that enable precise targeting under relatively well-controlled conditions. Analogous studies in vivo, where image-guided targeting is often not yet possible, rely on indirect, data-driven measures, and as a result such studies have been sparse and the dependence upon important experimental parameters has not been well studied. Here, using in vivo extracellular single-unit recordings in the topographically aligned rodent thalamocortical pathway, we sought to establish a general experimental and computational framework for inferring synaptic connectivity. Specifically, attacking this problem within a statistical signal detection framework utilizing experimentally recorded data in the ventral-posterior medial (VPm) region of the thalamus and the homologous region in layer 4 of primary somatosensory cortex (S1) revealed a trade-off between network activity levels needed for the data-driven inference and synchronization of nearby neurons within the population that results in masking of synaptic relationships. Here, we provide a framework for establishing connectivity in multisite, multielectrode recordings based on statistical inference, setting the stage for large-scale assessment of synaptic connectivity within and across brain structures. Despite the fact that all brain function relies on the long-range transfer of information across different regions, the tools enabling us to measure connectivity across brain structures are lacking. Here, we provide a statistical framework for identifying and assessing potential monosynaptic connectivity across neuronal circuits from population spiking activity that generalizes to large-scale recording technologies that will help us to better understand the signaling within networks that underlies perception and behavior.
Topics: Animals; Electric Stimulation; Electrocorticography; Evoked Potentials; Female; Male; Mice, Inbred C57BL; Nerve Net; Optical Imaging; Rats; Rats, Sprague-Dawley; Somatosensory Cortex; Synaptic Transmission; Thalamus; Vibrissae; Mice
PubMed: 33978507
DOI: 10.1152/jn.00591.2020 -
Cell Reports Apr 2024To meet the high energy demands of brain function, cerebral blood flow (CBF) parallels changes in neuronal activity by a mechanism known as neurovascular coupling (NVC)....
To meet the high energy demands of brain function, cerebral blood flow (CBF) parallels changes in neuronal activity by a mechanism known as neurovascular coupling (NVC). However, which neurons play a role in mediating NVC is not well understood. Here, we identify in mice and humans a specific population of cortical GABAergic neurons that co-express neuronal nitric oxide synthase and tachykinin receptor 1 (Tacr1). Through whole-tissue clearing, we demonstrate that Tacr1 neurons extend local and long-range projections across functionally connected cortical areas. We show that whisker stimulation elicited Tacr1 neuron activity in the barrel cortex through feedforward excitatory pathways. Additionally, through optogenetic experiments, we demonstrate that Tacr1 neurons are instrumental in mediating CBF through the relaxation of mural cells in a similar fashion to whisker stimulation. Finally, by electron microscopy, we observe that Tacr1 processes contact astrocytic endfeet. These findings suggest that Tacr1 neurons integrate cortical activity to mediate NVC.
Topics: Animals; Mice; Neurovascular Coupling; Humans; Neurons; Vibrissae; Mice, Inbred C57BL; GABAergic Neurons; Male; Cerebral Cortex; Cerebrovascular Circulation; Nitric Oxide Synthase Type I
PubMed: 38512868
DOI: 10.1016/j.celrep.2024.113970 -
Anatomical Record (Hoboken, N.J. : 2007) Mar 2022Extant members of Paenungulata (sirenians, proboscideans, and hyracoideans) form a monophyletic clade which originated in Africa. While paenungulates are all... (Review)
Review
Extant members of Paenungulata (sirenians, proboscideans, and hyracoideans) form a monophyletic clade which originated in Africa. While paenungulates are all herbivorous, they differ greatly in size, life history, and habitat. Therefore, we would expect both phylogenetically related similarities and ecologically driven differences in their use and specializations of sensory systems, especially in adaptations in sirenians related to their fully aquatic habitat. Here we review what is known about the sensory modalities of this clade in an attempt to better elucidate their sensory adaptations. Manatees have a higher frequency range for hearing than elephants, who have the best low-frequency hearing range known to mammals, while the hearing range of hyraxes is unknown. All paenungulates have vibrissae assisting in tactile abilities such as feeding and navigating the environment and share relatively small eyes and dichromatic vision. Taste buds are present in varying quantities in all three orders. While the olfactory abilities of manatees and hyraxes are unknown, elephants have an excellent sense of smell which is reflected by having the relatively largest cranial nerve related to olfaction among the three lineages. Manatees have the relatively largest trigeminal nerve-the nerve responsible for, among other things, mystacial vibrissae-while hyraxes have the relatively largest optic nerve (and therefore, presumably, the best vision) among the Paenungulata. All three orders have diverged significantly; however, they still retain some anatomical and physiological adaptations in common with regard to sensory abilities.
Topics: Animals; Elephants; Mammals; Phylogeny; Vibrissae
PubMed: 34424615
DOI: 10.1002/ar.24741 -
Nature Communications Oct 2021Identical physical inputs do not always evoke identical percepts. To investigate the role of stimulus history in tactile perception, we designed a task in which rats had...
Identical physical inputs do not always evoke identical percepts. To investigate the role of stimulus history in tactile perception, we designed a task in which rats had to judge each vibrissal vibration, in a long series, as strong or weak depending on its mean speed. After a low-speed stimulus (trial n - 1), rats were more likely to report the next stimulus (trial n) as strong, and after a high-speed stimulus, they were more likely to report the next stimulus as weak, a repulsive effect that did not depend on choice or reward on trial n - 1. This effect could be tracked over several preceding trials (i.e., n - 2 and earlier) and was characterized by an exponential decay function, reflecting a trial-by-trial incorporation of sensory history. Surprisingly, the influence of trial n - 1 strengthened as the time interval between n - 1 and n grew. Human subjects receiving fingertip vibrations showed these same key findings. We are able to account for the repulsive stimulus history effect, and its detailed time scale, through a single-parameter model, wherein each new stimulus gradually updates the subject's decision criterion. This model points to mechanisms underlying how the past affects the ongoing subjective experience.
Topics: Animals; Behavior; Humans; Judgment; Male; Memory, Short-Term; Neural Networks, Computer; Neurons; Perception; Rats; Reward; Touch Perception; Vibration; Vibrissae
PubMed: 34654804
DOI: 10.1038/s41467-021-26104-2 -
Progress in Neurobiology Jun 2021Our understanding of the neural basis of somatosensation is based largely on studies of the whisker system of mice and rats and the hands of macaque monkeys. Results... (Review)
Review
Our understanding of the neural basis of somatosensation is based largely on studies of the whisker system of mice and rats and the hands of macaque monkeys. Results across these animal models are often interpreted as providing direct insight into human somatosensation. Work on these systems has proceeded in parallel, capitalizing on the strengths of each model, but has rarely been considered as a whole. This lack of integration promotes a piecemeal understanding of somatosensation. Here, we examine the functions and morphologies of whiskers of mice and rats, the hands of macaque monkeys, and the somatosensory neuraxes of these three species. We then discuss how somatosensory information is encoded in their respective nervous systems, highlighting similarities and differences. We reflect on the limitations of these models of human somatosensation and consider key gaps in our understanding of the neural basis of somatosensation.
Topics: Animals; Haplorhini; Mice; Models, Animal; Rats; Somatosensory Cortex; Vibrissae
PubMed: 33587956
DOI: 10.1016/j.pneurobio.2021.102008 -
Sensors (Basel, Switzerland) Apr 2022Whisker sensors are a class of tactile sensors that have recently attracted attention. Inspired by mammals' whiskers known as mystacial vibrissae, they have displayed... (Review)
Review
Whisker sensors are a class of tactile sensors that have recently attracted attention. Inspired by mammals' whiskers known as mystacial vibrissae, they have displayed tremendous potential in a variety of applications e.g., robotics, underwater vehicles, minimally invasive surgeries, and leak detection. This paper provides a supplement to the recent tactile sensing techniques' designs of whiskers that only sense at their base, as well as the materials employed, and manufacturing techniques. The article delves into the technical specifications of these sensors, such as the resolution, measurement range, sensitivity, durability, and recovery time, which determine their performance. The sensors' sensitivity varies depending on the measured physical quantity; for example, the pressure sensors had an intermediate sensitivity of 58%/Pa and a response time of around 90 ms, whereas the force sensors that function based on piezoelectric effects exhibited good linearity in the measurements with a resolution of 3 µN and sensitivity of 0.1682 mV/µN. Some sensors were used to perform spatial mapping and the identification of the geometry and roughness of objects with a reported resolution of 25 nm. The durability and recovery time showed a wide range of values, with the maximum durability being 10,000 cycles and the shortest recovery time being 5 ms. Furthermore, the paper examines the fabrication of whiskers at the micro- and nanoscales, as well as their contributions to mechanical and thermal behavior. The commonly used manufacturing techniques of 3D printing, PDMS casting, and screen printing were used in addition to several micro and nanofabrication techniques such as photolithography, etching, and chemical vapor deposition. Lastly, the paper discusses the main potential applications of these sensors and potential research gaps in this field. In particular, the operation of whisker sensors under high temperatures or high pressure requires further investigation, as does the design of sensors to explore larger topologies.
Topics: Animals; Mammals; Printing, Three-Dimensional; Robotics; Touch; Vibrissae
PubMed: 35408319
DOI: 10.3390/s22072705 -
Nature Communications Sep 2023Excitatory spiny stellate neurons are prominently featured in the cortical circuits of sensory modalities that provide high salience and high acuity representations of...
Excitatory spiny stellate neurons are prominently featured in the cortical circuits of sensory modalities that provide high salience and high acuity representations of the environment. These specialized neurons are considered developmentally linked to bottom-up inputs from the thalamus, however, the molecular mechanisms underlying their diversification and function are unknown. Here, we investigated this in mouse somatosensory cortex, where spiny stellate neurons and pyramidal neurons have distinct roles in processing whisker-evoked signals. Utilizing spatial transcriptomics, we identified reciprocal patterns of gene expression which correlated with these cell-types and were linked to innervation by specific thalamic inputs during development. Genetic manipulation that prevents the acquisition of spiny stellate fate highlighted an important role for these neurons in processing distinct whisker signals within functional cortical columns, and as a key driver in the formation of specific whisker-related circuits in the cortex.
Topics: Animals; Vibrissae; Neurons; Pyramidal Cells; Neurites; Somatosensory Cortex; Thalamus
PubMed: 37770450
DOI: 10.1038/s41467-023-41749-x -
Pediatric Research Oct 2019Inflammation contributes to neonatal hypoxic-ischemic brain injury pathogenesis. We evaluated the neuroprotective efficacy of azithromycin, a safe, widely available...
BACKGROUND
Inflammation contributes to neonatal hypoxic-ischemic brain injury pathogenesis. We evaluated the neuroprotective efficacy of azithromycin, a safe, widely available antibiotic with anti-inflammatory properties, in a neonatal rodent hypoxic-ischemic brain injury model.
METHODS
Seven-day-old rats underwent right carotid artery ligation followed by 90-min 8% oxygen exposure; this procedure elicits quantifiable left forepaw functional impairment and right cerebral hemisphere damage. Sensorimotor function (vibrissae-stimulated forepaw placing, grip strength) and brain damage were compared in azithromycin- and saline-treated littermates 2-4 weeks later. Multiple treatment protocols were evaluated (variables included doses ranging from 15 to 45 mg/kg; treatment onset 15 min to 4 h post-hypoxia, and comparison of 1 vs. 3 injections).
RESULTS
All azithromycin doses improved function and reduced brain damage; efficacy was dose dependent, and declined with increasing treatment delay. Three azithromycin injections, administered over 48 h, improved performance on both function measures and reduced brain damage more than a single dose.
CONCLUSION
In this neonatal rodent model, azithromycin improved functional and neuropathology outcomes. If supported by confirmatory studies in complementary neonatal brain injury models, azithromycin could be an attractive candidate drug for repurposing and evaluation for neonatal neuroprotection in clinical trials.
Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Brain; Carotid Arteries; Disease Models, Animal; Drug Repositioning; Female; Hypoxia-Ischemia, Brain; Inflammation; Male; Neuroprotection; Neuroprotective Agents; Rats; Rats, Wistar
PubMed: 31100754
DOI: 10.1038/s41390-019-0408-6 -
Physiological Reviews Jan 2021The array of whiskers on the snout provides rodents with tactile sensory information relating to the size, shape and texture of objects in their immediate environment.... (Review)
Review
The array of whiskers on the snout provides rodents with tactile sensory information relating to the size, shape and texture of objects in their immediate environment. Rodents can use their whiskers to detect stimuli, distinguish textures, locate objects and navigate. Important aspects of whisker sensation are thought to result from neuronal computations in the whisker somatosensory cortex (wS1). Each whisker is individually represented in the somatotopic map of wS1 by an anatomical unit named a 'barrel' (hence also called barrel cortex). This allows precise investigation of sensory processing in the context of a well-defined map. Here, we first review the signaling pathways from the whiskers to wS1, and then discuss current understanding of the various types of excitatory and inhibitory neurons present within wS1. Different classes of cells can be defined according to anatomical, electrophysiological and molecular features. The synaptic connectivity of neurons within local wS1 microcircuits, as well as their long-range interactions and the impact of neuromodulators, are beginning to be understood. Recent technological progress has allowed cell-type-specific connectivity to be related to cell-type-specific activity during whisker-related behaviors. An important goal for future research is to obtain a causal and mechanistic understanding of how selected aspects of tactile sensory information are processed by specific types of neurons in the synaptically connected neuronal networks of wS1 and signaled to downstream brain areas, thus contributing to sensory-guided decision-making.
Topics: Animals; Brain Diseases; Brain-Computer Interfaces; Humans; Mice; Neural Pathways; Sensation; Signal Transduction; Somatosensory Cortex; Vibrissae
PubMed: 32816652
DOI: 10.1152/physrev.00019.2019 -
PloS One 2023Facial vibrissae (whiskers) are thin, tapered, flexible, hair-like structures that are an important source of tactile sensory information for many species of mammals. In...
Facial vibrissae (whiskers) are thin, tapered, flexible, hair-like structures that are an important source of tactile sensory information for many species of mammals. In contrast to insect antennae, whiskers have no sensors along their lengths. Instead, when a whisker touches an object, the resulting deformation is transmitted to mechanoreceptors in a follicle at the whisker base. Previous work has shown that the mechanical signals transmitted along the whisker will depend strongly on the whisker's geometric parameters, specifically on its taper (how diameter varies with arc length) and on the way in which the whisker curves, often called "intrinsic curvature." Although previous studies have largely agreed on how to define taper, multiple methods have been used to quantify intrinsic curvature. The present work compares and contrasts different mathematical approaches towards quantifying this important parameter. We begin by reviewing and clarifying the definition of "intrinsic curvature," and then show results of fitting whisker shapes with several different functions, including polynomial, fractional exponent, elliptical, and Cesàro. Comparisons are performed across ten species of whiskered animals, ranging from rodents to pinnipeds. We conclude with a discussion of the advantages and disadvantages of using the various models for different modeling situations. The fractional exponent model offers an approach towards developing a species-specific parameter to characterize whisker shapes within a species. Constructing models of how the whisker curves is important for the creation of mechanical models of tactile sensory acquisition behaviors, for studies of comparative evolution, morphology, and anatomy, and for designing artificial systems that can begin to emulate the whisker-based tactile sensing of animals.
Topics: Animals; Vibrissae; Mammals; Touch; Touch Perception; Caniformia
PubMed: 36607960
DOI: 10.1371/journal.pone.0269210