Interareal Synaptic Inputs Underlying Whisking-Related Activity in the Primary Somatosensory Barrel Cortex.

Body movements influence brain-wide neuronal activities. In the sensory cortex, thalamocortical bottom-up inputs and motor-sensory top-down inputs are thought to affect the dynamics of membrane potentials (Vm ) of neurons and change their processing of sensory information during movements. However, direct perturbation of the axons projecting to the sensory cortex from other remote areas during movements has remained unassessed, and therefore the interareal circuits generating motor-related signals in sensory cortices remain unclear. Using a Gi/o -coupled opsin, eOPN3, we here inhibited interareal signals incoming to the whisker primary somatosensory barrel cortex (wS1) of awake male mice and tested their effects on whisking-related changes in neuronal activities in wS1. Spontaneous whisking in air induced the changes in spike rates of a subset of wS1 neurons, which were accompanied by depolarization and substantial reduction of slow-wave oscillatory fluctuations of Vm Despite an extensive innervation, inhibition of inputs from the whisker primary motor cortex (wM1) to wS1 did not alter the spike rates and Vm dynamics of wS1 neurons during whisking. In contrast, inhibition of axons from the whisker-related thalamus (wTLM) and the whisker secondary somatosensory cortex (wS2) to wS1 largely attenuated the whisking-related supra- and sub-threshold Vm dynamics of wS1 neurons. Notably, silencing inputs from wTLM markedly decreased the modulation depth of whisking phase-tuned neurons in wS1, while inhibiting wS2 inputs did not impact the whisking variable tuning of wS1 neurons. Thus, sensorimotor integration in wS1 during spontaneous whisking is predominantly facilitated by direct synaptic inputs from wTLM and wS2 rather than from wM1.

Whiskers as hydrodynamic prey sensors in foraging seals.

The darkness of the deep ocean limits the vision of diving predators, except when prey emit bioluminescence. It is hypothesized that deep-diving seals rely on highly developed whiskers to locate their prey. However, if and how seals use their whiskers while foraging in natural conditions remains unknown. We used animal-borne tags to show that free-ranging elephant seals use their whiskers for hydrodynamic prey sensing. Small, cheek-mounted video loggers documented seals actively protracting their whiskers in front of their mouths with rhythmic whisker movement, like terrestrial mammals exploring their environment. Seals focused their sensing effort at deep foraging depths, performing prolonged whisker protraction to detect, pursue, and capture prey. Feeding-event recorders with light sensors demonstrated that bioluminescence contributed to only about 20% of overall foraging success, confirming that whiskers play the primary role in sensing prey. Accordingly, visual prey detection complemented and enhanced prey capture. The whiskers' role highlights an evolutionary alternative to echolocation for adapting to the extreme dark of the deep ocean environment, revealing how sensory abilities shape foraging niche segregation in deep-diving mammals. Mammals typically have mobile facial whiskers, and our study reveals the significant function of whiskers in the natural foraging behavior of a marine predator. We demonstrate the importance of field-based sensory studies incorporating multimodality to better understand how multiple sensory systems are complementary in shaping the foraging success of predators.

Interchangeable Role of Motor Cortex and Reafference for the Stable Execution of an Orofacial Action.

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.SIGNIFICANCE STATEMENT 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.

Continuous, multidimensional coding of 3D complex tactile stimuli by primary sensory neurons of the vibrissal system.

Across all sensory modalities, first-stage sensory neurons are an information bottleneck: they must convey all information available for an animal to perceive and act in its environment. Our understanding of coding properties of primary sensory neurons in the auditory and visual systems has been aided by the use of increasingly complex, naturalistic stimulus sets. By comparison, encoding properties of primary somatosensory afferents are poorly understood. Here, we use the rodent whisker system to examine how tactile information is represented in primary sensory neurons of the trigeminal ganglion (Vg). Vg neurons have long been thought to segregate into functional classes associated with separate streams of information processing. However, this view is based on Vg responses to restricted stimulus sets which potentially underreport the coding capabilities of these neurons. In contrast, the current study records Vg responses to complex three-dimensional (3D) stimulation while quantifying the complete 3D whisker shape and mechanics, thereby beginning to reveal their full representational capabilities. The results show that individual Vg neurons simultaneously represent multiple mechanical features of a stimulus, do not preferentially encode principal components of the stimuli, and represent continuous and tiled variations of all available mechanical information. These results directly contrast with proposed codes in which subpopulations of Vg neurons encode select stimulus features. Instead, individual Vg neurons likely overcome the information bottleneck by encoding large regions of a complex sensory space. This proposed tiled and multidimensional representation at the Vg directly constrains the computations performed by more central neurons of the vibrissotrigeminal pathway.

Cerebellar Purkinje cells can differentially modulate coherence between sensory and motor cortex depending on region and behavior.

Activity of sensory and motor cortices is essential for sensorimotor integration. In particular, coherence between these areas may indicate binding of critical functions like perception, motor planning, action, or sleep. Evidence is accumulating that cerebellar output modulates cortical activity and coherence, but how, when, and where it does so is unclear. We studied activity in and coherence between S1 and M1 cortices during whisker stimulation in the absence and presence of optogenetic Purkinje cell stimulation in crus 1 and 2 of awake mice, eliciting strong simple spike rate modulation. Without Purkinje cell stimulation, whisker stimulation triggers fast responses in S1 and M1 involving transient coherence in a broad spectrum. Simultaneous stimulation of Purkinje cells and whiskers affects amplitude and kinetics of sensory responses in S1 and M1 and alters the estimated S1-M1 coherence in theta and gamma bands, allowing bidirectional control dependent on behavioral context. These effects are absent when Purkinje cell activation is delayed by 20 ms. Focal stimulation of Purkinje cells revealed site specificity, with cells in medial crus 2 showing the most prominent and selective impact on estimated coherence, i.e., a strong suppression in the gamma but not the theta band. Granger causality analyses and computational modeling of the involved networks suggest that Purkinje cells control S1-M1 phase consistency predominantly via ventrolateral thalamus and M1. Our results indicate that activity of sensorimotor cortices can be dynamically and functionally modulated by specific cerebellar inputs, highlighting a widespread role of the cerebellum in coordinating sensorimotor behavior.

Preparation and Properties of High Sound-Absorbing Porous Ceramics Reinforced by In Situ Mullite Whisker from Construction Waste.

Porous sound absorption ceramic is one of the most promising materials for effectively eliminating noise pollution. However, its high production cost and low mechanical strength limit its practical applications. In this work, low-cost and in situ mullite whisker-reinforced porous sound-absorbing ceramics were prepared using recyclable construction waste and Al2O3 powder as the main raw materials, and AlF3 and CeO2 as the additives, respectively. The effects of CeO2 content, AlF3 content, and sintering temperature on the microstructure and properties of the porous ceramics were systematically investigated. The results showed that a small amount of CeO2 significantly promoted the growth of elongated mullite crystals in the resultant porous ceramics, decreased the growth temperature of the mullite whiskers, and significantly increased the biaxial flexural strength. When 2 wt.% CeO2 and 12 wt.% AlF3 were added to the system, mullite whiskers were successfully obtained at a sintering temperature of 1300 °C for 1 h, which exhibited excellent properties, including an open porosity of 56.4 ± 0.6%, an average pore size of 1.32-2.54 µm, a biaxial flexural strength of 23.7 ± 0.9 MPa, and a sound absorption coefficient of >0.8 at 800-4000 Hz.

Identification of a Developmental Switch in Information Transfer between Whisker S1 and S2 Cortex in Mice.

The whiskers of rodents are a key sensory organ that provides critical tactile information for animal navigation and object exploration throughout life. Previous work has explored the developmental sensory-driven activation of the primary sensory cortex processing whisker information (wS1), also called barrel cortex. This body of work has shown that the barrel cortex is already activated by sensory stimuli during the first postnatal week. However, it is currently unknown when over the course of development these stimuli begin being processed by higher-order cortical areas, such as secondary whisker somatosensory area (wS2). Here we investigate the developmental engagement of wS2 by whisker stimuli and the emergence of corticocortical communication from wS1 to wS2. Using in vivo wide-field imaging and multielectrode recordings in control and conditional KO mice of either sex with thalamocortical innervation defects, we find that wS1 and wS2 are able to process bottom-up information coming from the thalamus from birth. We also identify that it is only at the end of the first postnatal week that wS1 begins to provide functional excitation into wS2, switching to more inhibitory actions after the second postnatal week. Therefore, we have uncovered a developmental window when information transfer between wS1 and wS2 reaches mature function.SIGNIFICANCE STATEMENT At the end of the first postnatal week, the primary whisker somatosensory area starts providing excitatory input to the secondary whisker somatosensory area 2. This excitatory drive weakens during the second postnatal week and switches to inhibition in the adult.

Durative sleep fragmentation with or without hypertension suppress rapid eye movement sleep and generate cerebrovascular dysfunction.

Either hypertension or chronic insomnia is the risk factor of developing vascular dementia. Durative hypertension can induce vascular remodeling and is used for modeling small vessel disease in rodents. It remains undetermined if the combination of hypertension and sleep disturbance exacerbates vascular dysfunction or pathologies. Previously, we found chronic sleep fragmentation (SF) dampened cognition in young mice without disease predispositions. In the current study, we superimposed SF with hypertension modeling in young mice. Angiotensin II (AngII)-releasing osmotic mini pumps were subcutaneously implanted to generate persistent hypertension, while sham surgeries were performed as controls. Sleep fragmentation with repetitive arousals (10 s every 2 min) during light-on 12 h for consecutive 30 days, while mice undergoing normal sleep (NS) processes were set as controls. Sleep architectures, whisker-stimulated cerebral blood flow (CBF) changes, vascular responsiveness as well as vascular pathologies were compared among normal sleep plus sham (NS + sham), SF plus sham (SF + sham), normal sleep plus AngII (NS + AngII), and SF plus AngII (SF + AngII) groups. SF and hypertension both alter sleep structures, particularly suppressing REM sleep. SF no matter if combined with hypertension strongly suppressed whisker-stimulated CBF increase, suggesting the tight association with cognitive decline. Hypertension modeling sensitizes vascular responsiveness toward a vasoactive agent, Acetylcholine (ACh, 5 mg/ml, 10 µl) delivered via cisterna magna infusion, while SF exhibits a similar but much milder effect. None of the modeling above was sufficient to induce arterial or arteriole vascular remodeling, but SF or SF plus hypertension increased vascular network density constructed by all categories of cerebral vessels. The current study would potentially help understand the pathogenesis of vascular dementia, and the interconnection between sleep and vascular health.

Long and short whiskers differently guide snout/pellet interaction in rat oral grasping.

We studied the role of rat whisker/snout tactile sense during oral grasping, comparing control data with those obtained, respectively, 1-3 and 5-7 days after bilateral long or short whisker trimming and 3-5 and 8-10 days after bilateral infraorbital nerve (ION) severing. Two behavioural phases were identified: whisker-snout contact by nose-N or lip-L and snout-tongue contact. The second phase involved either: snout passing over stationary pellet (Still pellet); pellet rolling as the snout passed over it (Rolling pellet); pellet being pushed forward by the snout (Pushed pellet); or pellet being hit and pushed away (Hit/Lost pellet). In controls, success was 100%, with N-contact prevailing over L-contact in the first phase and Still pellet in the second. In long whisker-trimmed versus controls, success was still 100%, but L-contact increased in frequency, Pushed pellet prevailed and the second phase duration increased. In short whisker-trimmed versus controls, success remained 100%, with increased L-contact frequency; the first phase duration did not change, but the second phase increased since in pushed trials, the pellet rolled around the snout. In ION-severed versus controls, both phases changed drastically: L-contact frequency increased, Pushed pellet prevailed and contact was persistently maintained; Hit/Lost pellet emerged, Still and Rolling pellets disappeared and the oral-grasping sequence was not triggered. These results suggest that long and short whiskers, respectively, optimize the first and second phases of snout-pellet interaction and that whisker/snout sense is necessary to trigger oral grasping. Kinematic trajectory analysis supports the conclusion that movement from whisker to snout contact is an orientation response.

Comparative morphology of the whiskers and faces of mice (Mus musculus) and rats (Rattus norvegicus).

Understanding neural function requires quantification of the sensory signals that an animal's brain evolved to interpret. These signals in turn depend on the morphology and mechanics of the animal's sensory structures. Although the house mouse (Mus musculus) is one of the most common model species used in neuroscience, the spatial arrangement of its facial sensors has not yet been quantified. To address this gap, the present study quantifies the facial morphology of the mouse, with a particular focus on the geometry of its vibrissae (whiskers). The study develops equations that establish relationships between the three-dimensional (3D) locations of whisker basepoints, whisker geometry (arclength, curvature) and the 3D angles at which the whiskers emerge from the face. Additionally, the positions of facial sensory organs are quantified relative to bregma-lambda. Comparisons with the Norway rat (Rattus norvegicus) indicate that when normalized for head size, the whiskers of these two species have similar spacing density. The rostral-caudal distances between facial landmarks of the rat are a factor of ∼2.0 greater than the mouse, while the scale of bilateral distances is larger and more variable. We interpret these data to suggest that the larger size of rats compared with mice is a derived (apomorphic) trait. As rodents are increasingly important models in behavioral neuroscience, the morphological model developed here will help researchers generate naturalistic, multimodal patterns of stimulation for neurophysiological experiments and allow the generation of synthetic datasets and simulations to close the loop between brain, body and environment.

Wavy changes in the whiskers of domestic cats are correlated with feline leukemia virus infection.

BACKGROUND: Feline leukemia virus (FeLV) is a retrovirus with global impact on the health of domestic cats and is usually examined by serology. In our daily clinical practice, we noticed that cats infected with FeLV often possess wavy whiskers (sinus hairs on the face). To investigate the relationship between wavy whiskers (WW) and FeLV infection, the association between the presence or absence of wavy changes in whiskers and serological FeLV infection was examined in a total of 358 cats including 56 cats possessing WW, using the chi-square test. The results of blood tests from 223 cases were subjected to multivariate analysis (logistic analysis). Isolated whiskers were observed under light microscopy, and upper lip tissues (proboscis) were subjected to histopathological and immunohistochemical analyses. RESULTS: The prevalence of WW was significantly correlated with FeLV antigen positivity in the blood. Of 56 cases with WW, 50 (89.3%) were serologically positive for FeLV. The significant association between WW and serological FeLV positivity was also confirmed by multivariate analysis. In WW, narrowing, degeneration, and tearing of the hair medulla were observed. Mild infiltration of mononuclear cells in the tissues, but no degeneration or necrosis, was found. By immunohistochemistry, FeLV antigens (p27, gp70 and p15E) were observed in various epithelial cells including the sinus hair follicular epithelium of the whisker. CONCLUSIONS: The data suggest that the wavy changes in whiskers, a unique and distinctive external sign on a cat's face, were associated with FeLV infection.

Effects on low threshold mechanoreceptors in whisker hair follicles by 5-HT, Cd2+, tetraethylammonium, 4-aminopyridine, and Ba2.

Low threshold mechanoreceptors (LTMRs) are important for environmental exploration, social interaction, and tactile discrimination. Whisker hair follicles are mechanical sensory organs in non-primate mammals that are functionally equivalent to human fingertips. Several functional types of LTMRs have been identified in rodent whisker hair follicles, including rapidly adapting (RA), slow adapting type 1 (SA1), and slowly adapting type 2 (SA2) LTMRs. Properties of these LTMRs have not been fully characterized. In the present study, we have used pressure-clamped single-fiber recording technique to record impulses of RA, SA1, and SA2 LTMRs in mouse whisker hair follicles, and tested effects of 5-HT, Cd2+, tetraethylammonium (TEA), 4-aminopyridine (4-AP), and Ba2+ on the LTMR impulses. We show that 5-HT at 2 mM suppresses SA1 impulses but has no effects on RA and SA2 impulses. Cd2+ at 100 µM suppresses both SA1 and SA2 impulses but has no effects on RA impulses. TEA at 10 mM has no effects on RA and SA1 impulses but increased SA2 impulses. However, TEA at 1 mM and 200 µM decreases SA2 impulses. 4-AP at 1 mM suppresses both SA1 and SA2 impulses but has no effects on RA impulses. Ba2+ at 5 mM increases both RA and SA1 impulses but suppresses SA2 impulses. Collectively, RA, SA1, and SA2 LTMRs show distinct pharmacological properties, suggesting that these LTMRs may use different mechanisms to tune their mechanical signaling.

Sensory deprivation leads to subpopulation-specific changes in layer 6 corticothalamic cells.

The effect of sensory deprivation on anatomical and physiological properties in two genetically defined types of layer 6 corticothalamic pyramidal cells in mouse somatosensory barrel cortex was investigated using in vitro electrophysiology. The two types analysed were the L6-Ntsr1 subtype, found preferentially in the upper region of layer 6 and projecting to both ventral posterior medial nucleus of the thalamus and posterior medial nucleus of the thalamus, and the L6-Drd1a subtype, located mostly in the lower regions of layer 6 and projecting to posterior medial nucleus. We found that the apical dendrite in L6-Ntsr1 cells is longer and more branched, compared with L6-Drd1a cells, and that the increase in firing frequency with increasing current stimulation is steeper in L6-Drd1a cells. Sensory deprivation was achieved clipping one row of whiskers from birth until the day of experiment (16 ± 2 days). Mice of this age are actively exploring. In L6-Ntsr1, but not in L6-Drd1a cells, sensory deprivation decreased apical and basal dendrite outgrowth, and calcium influx evoked by backpropagating action potentials. These results contribute to the ongoing functional characterisation of corticothalamic layer 6 cells and indicate differences in the postnatal cortical refinement of two distinct corticothalamic circuits.

Cortical control of whisker movement.

Facial muscles drive whisker movements, which are important for active tactile sensory perception in mice and rats. These whisker muscles are innervated by cholinergic motor neurons located in the lateral facial nucleus. The whisker motor neurons receive synaptic inputs from premotor neurons, which are located within the brain stem, the midbrain, and the neocortex. Complex, distributed neural circuits therefore regulate whisker movement during behavior. This review focuses specifically on cortical whisker motor control. The whisker primary motor cortex (M1) strongly innervates brain stem reticular nuclei containing whisker premotor neurons, which might form a central pattern generator for rhythmic whisker protraction. In a parallel analogous pathway, the whisker primary somatosensory cortex (S1) strongly projects to the brain stem spinal trigeminal interpolaris nucleus, which contains whisker premotor neurons innervating muscles for whisker retraction. These anatomical pathways may play important functional roles, since stimulation of M1 drives exploratory rhythmic whisking, whereas stimulation of S1 drives whisker retraction.

A model of lateral interactions as the origin of multiwhisker receptive fields in rat barrel cortex.

While cells within barrel cortex respond primarily to deflections of their principal whisker (PW), they also exhibit responses to non-principal, or adjacent, whiskers (AWs), albeit responses with diminished amplitudes and longer latencies. The origin of multiwhisker receptive fields of barrel cells remains a point of controversy within the experimental literature, with three contending possibilities: (i) barrel cells inherit their AW responses from the AW responses of thalamocortical (TC) cells within their aligned barreloid; (ii) the axons of TC cells within a barreloid ramify to innervate multiple barrels, rather than only terminating within their aligned barrel; (iii) lateral intracortical transmission between barrels conveys AW responsivity to barrel cells. In this work, we develop a detailed, biologically plausible model of multiple barrels in order to examine possibility (iii); in order to isolate the dynamics that possibility (iii) entails, we incorporate lateral connections between barrels while assuming that TC cells respond only to their PW and that TC cell axons are confined to their home barrel. We show that our model is capable of capturing a broad swath of experimental observations on multiwhisker receptive field dynamics within barrels, and we compare and contrast the dynamics of this model with model dynamics from prior work in which employ a similar general modeling strategy to examine possibility (i).

Early alterations of the neuronal network processing whisker-related sensory signal during absence epileptogenesis.

OBJECTIVE: Epileptogenesis is the particular process during which the epileptic network builds up progressively before the onset of the first seizures. Whether physiological functions are impacted by this development of epilepsy remains unclear. To explore this question, we used Genetic Absence Epilepsy Rats From Strasbourg (GAERS), in which spike-and-wave discharges are initiated in the whisker primary somatosensory cortex (wS1) and first occur during cortical maturation. We studied the development of both the epileptic and the physiological wS1 circuits during cortical maturation to understand the interactions between them and the consequences for the animals' behavior. METHODS: In sedated and immobilized rat pups, we recorded in vivo epileptic and whisker sensory evoked activities across the wS1 and thalamus using multicontact electrodes. We compared sensory evoked potentials based on current source density analysis. We then analyzed the multiunit activities evoked by whisker stimulation in GAERS and control rats. Finally, we evaluated behavioral performance dependent on the functionality of the wS1 cortex using the gap-crossing task. RESULTS: We showed that the epileptic circuit changed during the epileptogenesis period in GAERS, by involving different cortical layers of wS1. Neuronal activities evoked by whisker stimulation were reduced in the wS1 cortex at P15 and P30 in GAERS but increased in the ventral posteromedial nucleus of the thalamus at P15 and in the posterior medial nucleus at P30, when compared to control rats. Finally, we observed lower performance in GAERS versus controls, at both P15 and P30, in a whisker-mediated behavioral task. SIGNIFICANCE: Our data show that the functionality of wS1 cortex and thalamus is altered early during absence epileptogenesis in GAERS and then evolves before spike-and-wave discharges are fully expressed. They suggest that the development of the pathological circuit disturbs the physiological one and may be responsible for both the emergence of seizures and associated comorbidities.

Establishment of Angora rabbits' whisker hair follicle model and optimal culture conditions.

To establish the model of whisker hair follicle culture in vitro and explore the best culture conditions, the whisker hair follicles of Angora rabbits were separated with stereomicroscope and cultured in William's E, DMEM, MEM media. The surface of the cultured whisker hair follicles was not damaged due to manual operation, resulting in the hair shaft's growth. This indicated the success of the in vitro whisker hair follicle model. The hair shaft grew at the fastest rate in the William's E culture (p < 0.05), which was significantly higher than that in the DMEM and MEM media. The hematoxylin-eosin results showed that compared to the William's E group, the atrophy of whisker hair follicles in the DMEM and MEM media was evident, especially in the MEM medium. PCNA immunofluorescence staining was employed to detect the expression of whisker hair follicles. The results showed that the PCNA positive expression of the William's E group was significantly stronger than that of the DMEM and MEM groups. Furthermore, CCK-8 and Annexin V-FITC/PI methods were used to detect the proliferation and apoptosis of the dermal papilla cells (DPCs). The results of this study provide a model for studying the hair growth of fur animals.

Cortical spreading depression can be triggered by sensory stimulation in primed wild type mouse brain: a mechanistic insight to migraine aura generation.

BACKGROUND: Unlike the spontaneously appearing aura in migraineurs, experimentally, cortical spreading depression (CSD), the neurophysiological correlate of aura is induced by non-physiological stimuli. Consequently, neural mechanisms involved in spontaneous CSD generation, which may provide insight into how migraine starts in an otherwise healthy brain, remain largely unclear. We hypothesized that CSD can be physiologically induced by sensory stimulation in primed mouse brain. METHODS: Cortex was made susceptible to CSD with partial inhibition of Na+/K+-ATPase by epidural application of a low concentration of Na+/K+-ATPase blocker ouabain, allowing longer than 30-min intervals between CSDs or by knocking-down α2 subunit of Na+/K+-ATPase, which is crucial for K+ and glutamate re-uptake, with shRNA. Stimulation-triggered CSDs and extracellular K+ changes were monitored in vivo electrophysiologically and a K+-sensitive fluoroprobe (IPG-4), respectively. RESULTS: After priming with ouabain, photic stimulation significantly increased the CSD incidence compared with non-stimulated animals (44.0 vs. 4.9%, p < 0.001). Whisker stimulation also significantly increased the CSD incidence, albeit less effectively (14.9 vs. 2.4%, p = 0.02). Knocking-down Na+/K+-ATPase (50% decrease in mRNA) lowered the CSD threshold in all mice tested with KCl but triggered CSDs in 14.3% and 16.7% of mice with photic and whisker stimulation, respectively. Confirming Na+/K+-ATPase hypofunction, extracellular K+ significantly rose during sensory stimulation after ouabain or shRNA treatment unlike controls. In line with the higher CSD susceptibility observed, K+ rise was more prominent after ouabain. To gain insight to preventive mechanisms reducing the probability of stimulus-evoked CSDs, we applied an A1-receptor antagonist (DPCPX) to the occipital cortex, because adenosine formed during stimulation from ATP can reduce CSD susceptibility. DPCPX induced spontaneous CSDs but only small-DC shifts along with suppression of EEG spikes during photic stimulation, suggesting that the inhibition co-activated with sensory stimulation could limit CSD ignition when K+ uptake was not sufficiently suppressed as with ouabain. CONCLUSIONS: Normal brain is well protected against CSD generation. For CSD to be ignited under physiological conditions, priming and predisposing factors are required as seen in migraine patients. Intense sensory stimulation has potential to trigger CSD when co-existing conditions bring extracellular K+ and glutamate concentrations over CSD-ignition threshold and stimulation-evoked inhibitory mechanisms are overcome.

Simple and complex spike responses of mouse cerebellar Purkinje neurons to regular trains and omissions of somatosensory stimuli.

Cerebellar Purkinje neurons help compute absolute subsecond timing, but how their firing is affected during repetitive sensory stimulation with consistent subsecond intervals remains unaddressed. Here, we investigated how simple and complex spikes of Purkinje cells change during regular application of air puffs (3.3 Hz for ∼4 min) to the whisker pad of awake, head-fixed female mice. Complex spike responses fell into two categories: those in which firing rates increased (at ∼50 ms) and then fell [complex spike elevated (CxSE) cells] and those in which firing rates decreased (at ∼70 ms) and then rose [complex spike reduced (CxSR) cells]. Both groups had indistinguishable rates of basal complex (∼1.7 Hz) and simple (∼75 Hz) spikes and initially responded to puffs with a well-timed sensory response, consisting of a short-latency (∼15 ms), transient (4 ms) suppression of simple spikes. CxSE more than CxSR cells, however, also showed a longer-latency increase in simple spike rate, previously shown to reflect motor command signals. With repeated puffs, basal simple spike rates dropped greatly in CxSR but not CxSE cells; complex spike rates remained constant, but their temporal precision rose in CxSR cells and fell in CxSE cells. Also over time, transient simple spike suppression gradually disappeared in CxSE cells, suggesting habituation, but remained stable in CxSR cells, suggesting reliable transmission of sensory stimuli. During stimulus omissions, both categories of cells showed complex spike suppression with different latencies. The data indicate two modes by which Purkinje cells transmit regular repetitive stimuli, distinguishable by their climbing fiber signals.NEW & NOTEWORTHY Responses of cerebellar Purkinje cells in awake mice form two categories defined by complex spiking during regular trains of brief, somatosensory stimuli. Cells in which complex spike probability first increases or decreases show simple spike suppressions that habituate or persist, respectively. Stimulus omissions alter complex spiking. The results provide evidence for differential suppression of olivary cells during sensory stimulation and omissions and illustrate that climbing fiber innervation defines Purkinje cell responses to repetitive stimuli.

Multiple Morphological Factors Underlie Experience-Dependent Cross-Modal Plasticity in the Developing Sensory Cortices.

Sensory experience regulates the structural and functional wiring of sensory cortices. In previous work, we showed that whisker deprivation (WD) from birth not only reduced excitatory synaptic transmission of layer (L) 2/3 pyramidal neurons of the correspondent barrel cortex in mice, but also cross-modally reduced synaptic transmission of L2/3 pyramidal neurons in other sensory cortices. Here, we used in utero electroporation, in combination with optical clearing, to examine the main morphological components regulating neural circuit wiring, namely presynaptic bouton density, spine density, as well as dendrite and axon arbor lengths. We found that WD from P0 to P14 reduced presynaptic bouton density in both L4 and L2/3 inputs to L2/3 pyramidal neurons, as well as spine density across the dendritic tree of L2/3 pyramidal neurons, in the barrel field of the primary somatosensory cortex. The cross-modal effects in the primary auditory cortex were manifested mostly as reduced dendrite and axon arbor size, as well as reduced bouton density of L2/3 inputs. Increasing sensory experience by rearing mice in an enriched environment rescued the effects of WD. Together, these results demonstrate that multiple morphological factors contribute to experience-dependent structural plasticity during early wiring of the sensory cortices.