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Current Biology : CB Aug 2023Vasoactive intestinal peptide (VIP) interneurons in sensory cortex modulate sensory responses based on global exploratory behavior and arousal state, but their function...
Vasoactive intestinal peptide (VIP) interneurons in sensory cortex modulate sensory responses based on global exploratory behavior and arousal state, but their function during non-exploratory, goal-directed behavior is not well understood. In particular, whether VIP cells are activated by sensory cues, reward-seeking actions, or directly by reinforcement is unclear. We trained mice on a Go/NoGo whisker touch detection task that included a delay period and other features designed to separate sensory-evoked, action-related, and reward-related neural activity. Mice had to lick in response to a whisker stimulus to receive a variable-sized reward. Using two-photon calcium imaging, we measured ΔF/F responses of L2/3 VIP neurons in whisker somatosensory cortex (S1) during behavior. In both expert and novice mice, VIP cells were strongly activated by whisker stimuli and goal-directed actions (licking), but not by reinforcement. VIP cells showed somatotopic whisker tuning that was spatially organized relative to anatomical columns in S1, unlike lick-related signals which were spatially widespread. In expert mice, lick-related VIP responses were suppressed, not enhanced, when a reward was delivered, and the amount of suppression increased with reward size. This reward-related suppression was not seen in novice mice, where reward delivery was not yoked to licking. These results indicate that besides arousal and global state variables, VIP cells are activated by local sensory features and goal-directed actions, but not directly by reinforcement. Instead, our results are consistent with a role for VIP cells in encoding the expectation of reward associated with motor actions.
Topics: Mice; Animals; Vasoactive Intestinal Peptide; Interneurons; Neurons; Somatosensory Cortex; Reward; Vibrissae
PubMed: 37499665
DOI: 10.1016/j.cub.2023.06.086 -
Cell Reports Methods Jun 2023Here, we present an X-ray-visible neural tracer, referred to as DiI-CT, which is based on the well-established lipophilic indocarbocyanine dye DiI, to which we...
Here, we present an X-ray-visible neural tracer, referred to as DiI-CT, which is based on the well-established lipophilic indocarbocyanine dye DiI, to which we conjugated two iodine atoms. The tracer is visible with microfocus computed tomography (microCT) imaging and shares the excellent fluorescent tracing properties of DiI. We document the discovery potential of DiI-CT by analyzing the vibrissa follicle-sinus complex, a structure where visual access is poor and 3D tissue structure matters and reveal innervation patterns of the intact follicle in unprecedented detail. In the brain, DiI-CT tracing holds promise for verification evaluation of indirect connectivity measures, such as diffusion tensor imaging. We conclude that the bimodal dye DiI-CT opens new avenues for neuroanatomy.
Topics: X-Rays; Carbocyanines; Diffusion Tensor Imaging; Fluorescent Dyes; Optical Imaging; Tomography, X-Ray Computed
PubMed: 37426763
DOI: 10.1016/j.crmeth.2023.100486 -
PLoS Biology Jul 2023We know little about mammalian anemotaxis or wind sensing. Recently, however, Hartmann and colleagues showed whisker-based anemotaxis in rats. To investigate how...
We know little about mammalian anemotaxis or wind sensing. Recently, however, Hartmann and colleagues showed whisker-based anemotaxis in rats. To investigate how whiskers sense airflow, we first tracked whisker tips in anesthetized rats under low (0.5 m/s) and high (1.5 m/s) airflow. Whisker tips showed increasing movement from low to high airflow conditions, with all whisker tips moving during high airflow. Low airflow conditions-most similar to naturally occurring wind stimuli-engaged whisker tips differentially. Most whiskers moved little, but the long supra-orbital (lSO) whisker showed maximal displacement, followed by the α, β, and A1 whiskers. The lSO whisker differs from other whiskers in its exposed dorsal position, upward bending, length and thin diameter. Ex vivo extracted lSO whiskers also showed exceptional airflow displacement, suggesting whisker-intrinsic biomechanics mediate the unique airflow-sensitivity. Micro computed tomography (micro-CT) revealed that the ring-wulst-the follicle structure receiving the most sensitive afferents-was more complete/closed in the lSO, and other wind-sensitive whiskers, than in non-wind-sensitive whiskers, suggesting specialization of the supra-orbital for omni-directional sensing. We localized and targeted the cortical supra-orbital whisker representation in simultaneous Neuropixels recordings with D/E-row whisker barrels. Responses to wind-stimuli were stronger in the supra-orbital whisker representation than in D/E-row barrel cortex. We assessed the behavioral significance of whiskers in an airflow-sensing paradigm. We observed that rats spontaneously turn towards airflow stimuli in complete darkness. Selective trimming of wind-responsive whiskers diminished airflow turning responses more than trimming of non-wind-responsive whiskers. Lidocaine injections targeted to supra-orbital whisker follicles also diminished airflow turning responses compared to control injections. We conclude that supra-orbital whiskers act as wind antennae.
Topics: Rats; Animals; Vibrissae; X-Ray Microtomography; Somatosensory Cortex; Physical Stimulation; Movement; Mammals
PubMed: 37410722
DOI: 10.1371/journal.pbio.3002168 -
The Journal of Neuroscience : the... Jul 2023Animals interact with their environment through mechanically active, mobile sensors. The efficient use of these sensory organs implies the ability to track their...
Animals interact with their environment through mechanically active, mobile sensors. The efficient use of these sensory organs implies the ability to track their position; otherwise, perceptual stability or prehension would be profoundly impeded. The nervous system may keep track of the position of a sensorimotor organ via two complementary feedback mechanisms-peripheral reafference (external, sensory feedback) and efference copy (internal feedback). Yet, the potential contributions of these mechanisms remain largely unexplored. By training male rats to place one of their vibrissae within a predetermined angular range without contact, a task that depends on knowledge of vibrissa position relative to their face, we found that peripheral reafference is not required. The presence of motor cortex is not required either, except in the absence of peripheral reafference to maintain motor stability. Finally, the red nucleus, which receives descending inputs from motor cortex and cerebellum and projects to facial motoneurons, is critically involved in the execution of the vibrissa positioning task. All told, our results point toward the existence of an internal model that requires either peripheral reafference or motor cortex to optimally drive voluntary motion. How does an animal know where a mechanically active, mobile sensor lies relative to its body? We address this basic question in sensorimotor integration using the motion of the vibrissae in rats. We show that rats can learn to reliably position their vibrissae in the absence of sensory feedback or in the absence of motor cortex. Yet, when both sensory feedback and motor cortex are absent, motor precision is degraded. This suggests the existence of an internal model able to operate in closed- and open-loop modes, requiring either motor cortex or sensory feedback to maintain motor stability.
Topics: Rats; Animals; Male; Motor Cortex; Motor Neurons; Nervous System Physiological Phenomena; Cerebellum; Vibrissae; Somatosensory Cortex
PubMed: 37400255
DOI: 10.1523/JNEUROSCI.2089-22.2023 -
Frontiers in Neural Circuits 2023Memories associated to signals have been proven to rely on the recruitment of associative memory neurons that are featured by mutual synapse innervations among...
Memories associated to signals have been proven to rely on the recruitment of associative memory neurons that are featured by mutual synapse innervations among cross-modal cortices. Whether the consolidation of associative memory is endorsed by the upregulation of associative memory neurons in an intramodal cortex remains to be examined. The function and interconnection of associative memory neurons were investigated by electrophysiology and adeno-associated virus-mediated neural tracing in those mice that experienced associative learning by pairing the whisker tactile signal and the olfactory signal. Our results show that odorant-induced whisker motion as a type of associative memory is coupled with the enhancement of whisking-induced whisker motion. In addition to some barrel cortical neurons encoding both whisker and olfactory signals, i.e., their recruitment as associative memory neurons, the synapse interconnection and spike-encoding capacity of associative memory neurons within the barrel cortex are upregulated. These upregulated alternations were partially observed in the activity-induced sensitization. In summary, associative memory is mechanistically based on the recruitment of associative memory neurons and the upregulation of their interactions in intramodal cortices.
Topics: Mice; Animals; Neurons; Conditioning, Classical; Up-Regulation; Synapses; Smell; Vibrissae; Somatosensory Cortex
PubMed: 37396398
DOI: 10.3389/fncir.2023.1189907 -
Frontiers in Microbiology 2023Herpes simplex virus 1 (HSV-1) is a widely distributed virus. HSV-1 is a growing public health concern due to the emergence of drug-resistant strains and the current...
Herpes simplex virus 1 (HSV-1) is a widely distributed virus. HSV-1 is a growing public health concern due to the emergence of drug-resistant strains and the current lack of a clinically specific drug for treatment. In recent years, increasing attention has been paid to the development of peptide antivirals. Natural host-defense peptides which have uniquely evolved to protect the host have been reported to have antiviral properties. Cathelicidins are a family of multi-functional antimicrobial peptides found in almost all vertebrate species and play a vital role in the immune system. In this study, we demonstrated the anti-HSV-1 effect of an antiviral peptide named WL-1 derived from human cathelicidin. We found that WL-1 inhibited HSV-1 infection in epithelial and neuronal cells. Furthermore, the administration of WL-1 improved the survival rate and reduced viral load and inflammation during HSV-1 infection via ocular scarification. Moreover, facial nerve dysfunction, involving the abnormal blink reflex, nose position, and vibrissae movement, and pathological injury were prevented when HSV-1 ear inoculation-infected mice were treated with WL-1. Together, our findings demonstrate that WL-1 may be a potential novel antiviral agent against HSV-1 infection-induced facial palsy.
PubMed: 37342565
DOI: 10.3389/fmicb.2023.1201505 -
PloS One 2023Neocortical neurons can increasingly be divided into well-defined classes, but their activity patterns during quantified behavior remain to be fully determined. Here, we...
Neocortical neurons can increasingly be divided into well-defined classes, but their activity patterns during quantified behavior remain to be fully determined. Here, we obtained membrane potential recordings from various classes of excitatory and inhibitory neurons located across different cortical depths in the primary whisker somatosensory barrel cortex of awake head-restrained mice during quiet wakefulness, free whisking and active touch. Excitatory neurons, especially those located superficially, were hyperpolarized with low action potential firing rates relative to inhibitory neurons. Parvalbumin-expressing inhibitory neurons on average fired at the highest rates, responding strongly and rapidly to whisker touch. Vasoactive intestinal peptide-expressing inhibitory neurons were excited during whisking, but responded to active touch only after a delay. Somatostatin-expressing inhibitory neurons had the smallest membrane potential fluctuations and exhibited hyperpolarising responses at whisking onset for superficial, but not deep, neurons. Interestingly, rapid repetitive whisker touch evoked excitatory responses in somatostatin-expressing inhibitory neurons, but not when the intercontact interval was long. Our analyses suggest that distinct genetically-defined classes of neurons at different subpial depths have differential activity patterns depending upon behavioral state providing a basis for constraining future computational models of neocortical function.
Topics: Animals; Membrane Potentials; Vibrissae; Touch; Neurons; Somatostatin
PubMed: 37311008
DOI: 10.1371/journal.pone.0287174 -
Communications Biology Jun 2023Behavior and innervation suggest a high tactile sensitivity of elephant trunks. To clarify the tactile trunk periphery we studied whiskers with the following findings....
Behavior and innervation suggest a high tactile sensitivity of elephant trunks. To clarify the tactile trunk periphery we studied whiskers with the following findings. Whisker density is high at the trunk tip and African savanna elephants have more trunk tip whiskers than Asian elephants. Adult elephants show striking lateralized whisker abrasion caused by lateralized trunk behavior. Elephant whiskers are thick and show little tapering. Whisker follicles are large, lack a ring sinus and their organization varies across the trunk. Follicles are innervated by ~90 axons from multiple nerves. Because elephants don't whisk, trunk movements determine whisker contacts. Whisker-arrays on the ventral trunk-ridge contact objects balanced on the ventral trunk. Trunk whiskers differ from the mobile, thin and tapered facial whiskers that sample peri-rostrum space symmetrically in many mammals. We suggest their distinctive features-being thick, non-tapered, lateralized and arranged in specific high-density arrays-evolved along with the manipulative capacities of the trunk.
Topics: Animals; Vibrissae; Elephants; Touch; Mammals; Movement
PubMed: 37291455
DOI: 10.1038/s42003-023-04945-5 -
Life (Basel, Switzerland) May 2023Exposure to space galactic cosmic radiation is a principal consideration for deep space missions. While the effects of space irradiation on the nervous system are not...
Exposure to space galactic cosmic radiation is a principal consideration for deep space missions. While the effects of space irradiation on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Cognitive health implications put humans and missions at risk, and with the upcoming Artemis missions in which female crew will play a major role, advance critical analysis of the neurological and performance responses of male and female rodents to space radiation is vital. Here, we tested the hypothesis that simulated Galactic Cosmic Radiation (GCRSim) exposure disrupts species-typical behavior in mice, including burrowing, rearing, grooming, and nest-building that depend upon hippocampal and medial prefrontal cortex circuitry. Behavior comprises a remarkably well-integrated representation of the biology of the whole animal that informs overall neural and physiological status, revealing functional impairment. We conducted a systematic dose-response analysis of mature (6-month-old) male and female mice exposed to either 5, 15, or 50 cGy 5-ion GCRSim (H, Si, He, O, Fe) at the NASA Space Radiation Laboratory (NSRL). Behavioral performance was evaluated at 72 h (acute) and 91-days (delayed) postradiation exposure. Specifically, species-typical behavior patterns comprising burrowing, rearing, and grooming as well as nest building were analyzed. A Neuroscore test battery (spontaneous activity, proprioception, vibrissae touch, limb symmetry, lateral turning, forelimb outstretching, and climbing) was performed at the acute timepoint to investigate early sensorimotor deficits postirradiation exposure. Nest construction, a measure of neurological and organizational function in rodents, was evaluated using a five-stage Likert scale 'Deacon' score that ranged from 1 (a low score where the Nestlet is untouched) to 5 (a high score where the Nestlet is completely shredded and shaped into a nest). Differential acute responses were observed in females relative to males with respect to species-typical behavior following 15 cGy exposure while delayed responses were observed in female grooming following 50 cGy exposure. Significant sex differences were observed at both timepoints in nest building. No deficits in sensorimotor behavior were observed via the Neuroscore. This study revealed subtle, sexually dimorphic GCRSim exposure effects on mouse behavior. Our analysis provides a clearer understanding of GCR dose effects on species typical, sensorimotor and organizational behaviors at acute and delayed timeframes postirradiation, thereby setting the stage for the identification of underlying cellular and molecular events.
PubMed: 37240858
DOI: 10.3390/life13051214 -
PLoS Biology May 2023The superior colliculus (SC), a conserved midbrain node with extensive long-range connectivity throughout the brain, is a key structure for innate behaviors. Descending...
The superior colliculus (SC), a conserved midbrain node with extensive long-range connectivity throughout the brain, is a key structure for innate behaviors. Descending cortical pathways are increasingly recognized as central control points for SC-mediated behaviors, but how cortico-collicular pathways coordinate SC activity at the cellular level is poorly understood. Moreover, despite the known role of the SC as a multisensory integrator, the involvement of the SC in the somatosensory system is largely unexplored in comparison to its involvement in the visual and auditory systems. Here, we mapped the connectivity of the whisker-sensitive region of the SC in mice with trans-synaptic and intersectional tracing tools and in vivo electrophysiology. The results reveal a novel trans-collicular connectivity motif in which neurons in motor- and somatosensory cortices impinge onto the brainstem-SC-brainstem sensory-motor arc and onto SC-midbrain output pathways via only one synapse in the SC. Intersectional approaches and optogenetically assisted connectivity quantifications in vivo reveal convergence of motor and somatosensory cortical input on individual SC neurons, providing a new framework for sensory-motor integration in the SC. More than a third of the cortical recipient neurons in the whisker SC are GABAergic neurons, which include a hitherto unknown population of GABAergic projection neurons targeting thalamic nuclei and the zona incerta. These results pinpoint a whisker region in the SC of mice as a node for the integration of somatosensory and motor cortical signals via parallel excitatory and inhibitory trans-collicular pathways, which link cortical and subcortical whisker circuits for somato-motor integration.
Topics: Mice; Animals; Vibrissae; Neurons; Superior Colliculi; Motor Cortex; Brain; Somatosensory Cortex
PubMed: 37205722
DOI: 10.1371/journal.pbio.3002126