-
Neuron Dec 2022Behavioral states can influence performance of goal-directed sensorimotor tasks. Yet, it is unclear how altered neuronal sensory representations in these states relate...
Behavioral states can influence performance of goal-directed sensorimotor tasks. Yet, it is unclear how altered neuronal sensory representations in these states relate to task performance and learning. We trained water-restricted mice in a two-whisker discrimination task to study cortical circuits underlying perceptual decision-making under different levels of thirst. We identified somatosensory cortices as well as the premotor cortex as part of the circuit necessary for task execution. Two-photon calcium imaging in these areas identified populations selective to sensory or motor events. Analysis of task performance during individual sessions revealed distinct behavioral states induced by decreasing levels of thirst-related motivation. Learning was better explained by improvements in motivational state control rather than sensorimotor association. Whisker sensory representations in the cortex were altered across behavioral states. In particular, whisker stimuli could be better decoded from neuronal activity during high task performance states, suggesting that state-dependent changes of sensory processing influence decision-making.
Topics: Mice; Animals; Motivation; Goals; Learning; Motor Cortex; Perception; Somatosensory Cortex; Vibrissae
PubMed: 36240769
DOI: 10.1016/j.neuron.2022.09.032 -
Scientific Data Oct 2022Mice adeptly use their whiskers to touch, recognize, and learn about objects in their environment. This behavior is enabled by computations performed by populations of...
Mice adeptly use their whiskers to touch, recognize, and learn about objects in their environment. This behavior is enabled by computations performed by populations of neurons in the somatosensory cortex. To understand these computations, we trained mice to use their whiskers to recognize different shapes while we recorded activity in the barrel cortex, which processes whisker input. Here, we present a large dataset of high-speed video of the whiskers, along with rigorous tracking of the entire extent of multiple whiskers and every contact they made on the shape. We used spike sorting to identify individual neurons, which responded with precise timing to whisker contacts and motion. These data will be useful for understanding the behavioral strategies mice use to explore objects, as well as the neuronal dynamics that mediate those strategies. In addition, our carefully curated labeled data could be used to develop new computer vision algorithms for tracking body posture, or for extracting responses of individual neurons from large-scale neural recordings.
Topics: Animals; Mice; Neurons; Somatosensory Cortex; Touch; Vibrissae; Visual Perception
PubMed: 36229608
DOI: 10.1038/s41597-022-01728-1 -
Journal of Dermatological Science Oct 2022Although vitamins or their derivatives (Vits), such as panthenyl ethyl ether, tocopherol acetate, and pyridoxine, have been widely used in topical hair care products,...
BACKGROUND
Although vitamins or their derivatives (Vits), such as panthenyl ethyl ether, tocopherol acetate, and pyridoxine, have been widely used in topical hair care products, their efficacy and mode of action have been insufficiently studied.
OBJECTIVE
To elucidate the biological influence of Vits on hair follicles and determine the underlying mechanisms.
METHODS
A mouse vibrissa hair follicle organ culture model was utilized to evaluate the effects of Vits on hair shaft elongation. Gene and protein expression analyses and histological investigations were conducted to elucidate the responsible mechanisms. A human hair follicle cell culture was used to assess the clinical relevance.
RESULTS
In organ culture models, the combination of panthenyl ethyl ether, tocopherol acetate, and pyridoxine (namely, PPT) supplementation significantly promoted hair shaft elongation. PPT treatment enhanced hair matrix cell proliferation by 1.9-fold compared to controls, as demonstrated by Ki67-positive immunoreactivity. PPT-treated mouse dermal papillae exhibited upregulated Placental growth factor (Plgf) by 1.6-fold compared to controls. Importantly, the addition of PlGF neutralizing antibodies to the ex vivo culture diminished the promotive effect on hair growth and increase in VEGFR-1 phosphorylation achieved by PPT. A VEGFR-1 inhibitor also inhibited the promotion of hair growth. Microarray analysis suggested synergistic summation of individual Vits' bioactivity, putatively explaining the effect of PPT. Moreover, PPT increased PlGF secretion in cultured human dermal papilla cells.
CONCLUSION
Our findings suggested that PPT promoted hair shaft elongation by activating PlGF/VEGFR-1 signalling. The current study can shed light on the previously underrepresented advantage of utilizing Vits in hair care products.
Topics: Humans; Female; Mice; Animals; Placenta Growth Factor; Vascular Endothelial Growth Factor Receptor-1; Vitamins; alpha-Tocopherol; Pyridoxine; Hair; Hair Follicle; Cells, Cultured; Vitamin A; Hair Preparations
PubMed: 36210234
DOI: 10.1016/j.jdermsci.2022.09.003 -
Scientific Reports Sep 2022Spontaneous activity during the early postnatal period is thought to be crucial for the establishment of mature neural circuits. It remains unclear if the peripheral...
Spontaneous activity during the early postnatal period is thought to be crucial for the establishment of mature neural circuits. It remains unclear if the peripheral structure of the developing somatosensory system exhibits spontaneous activity, similar to that observed in the retina and cochlea of developing mammals. By establishing an ex vivo calcium imaging system, here we found that neurons in the whisker-innervating region of the trigeminal ganglion (TG) of neonatal mice generate spontaneous activity. A small percentage of neurons showed some obvious correlated activity, and these neurons were mostly located close to one another. TG spontaneous activity was majorly exhibited by medium-to-large diameter neurons, a characteristic of mechanosensory neurons, and was blocked by chelation of extracellular calcium. Moreover, this activity was diminished by the adult stage. Spontaneous activity in the TG during the first postnatal week could be a source of spontaneous activity observed in the neonatal mouse barrel cortex.
Topics: Animals; Animals, Newborn; Calcium; Calcium, Dietary; Mammals; Trigeminal Ganglion; Vibrissae
PubMed: 36175429
DOI: 10.1038/s41598-022-20068-z -
Journal of Neurophysiology Nov 2022Spike-wave discharges (SWDs) are among the most prominent electrical signals recordable from the rat cerebrum. Increased by inbreeding, SWDs have served as an animal...
Spike-wave discharges (SWDs) are among the most prominent electrical signals recordable from the rat cerebrum. Increased by inbreeding, SWDs have served as an animal model of human genetic absence seizures. Yet, SWDs are ubiquitous in inbred and outbred rats, suggesting they reflect normal brain function. We hypothesized that SWDs represent oscillatory neural ensemble activity underlying sensory encoding. To test this hypothesis, we simultaneously mapped SWDs from wide areas (8 × 8 mm) of both hemispheres in anesthetized rats, using 256-electrode epicortical arrays that covered primary and secondary somatosensory, auditory and visual cortex bilaterally. We also recorded the laminar pattern of SWDs with linear microelectrode arrays. We compared the spatial and temporal organization of SWDs to somatosensory-evoked potentials (SEPs), as well as auditory- and visual-evoked potentials (AEPs and VEPs) to examine similarities and/or differences between sensory-evoked and spontaneous oscillations in the same animals. We discovered that SWDs are confined to the facial representation of primary and secondary somatosensory cortex (SI and SII, respectively), areas that are preferentially engaged during environmental exploration in the rat. Furthermore, these oscillations exhibit highly synchronized bilateral traveling waves in SI and SII, simultaneously forming closely matched spread patterns in both hemispheres. We propose that SWDs could reflect a previously unappreciated capacity for rat somatosensory cortex to perform precise spatial and temporal analysis of rapidly changing sensory input at the level of large neural ensembles synchronized both within and between the cerebral hemispheres. We simultaneously mapped electrocortical SWDs from both cerebral hemispheres of Sprague-Dawley rats and discovered that they reflect systematic activation of the facial representation of somatosensory cortex. SWDs form mirror spatiotemporal patterns in both hemispheres that are precisely aligned in both space and time. Our data suggest that SWDs may reflect a substrate by which large neural ensembles perform precise spatiotemporal processing of rapidly changing somatosensory input.
Topics: Animals; Rats; Electroencephalography; Epilepsy, Absence; Evoked Potentials, Somatosensory; Rats, Sprague-Dawley; Somatosensory Cortex
PubMed: 36169203
DOI: 10.1152/jn.00303.2022 -
Nature Communications Sep 2022Sensory input arrives from thalamus in cortical layer (L) 4, which outputs predominantly to superficial layers. L4 to L2 thus constitutes one of the earliest cortical...
Sensory input arrives from thalamus in cortical layer (L) 4, which outputs predominantly to superficial layers. L4 to L2 thus constitutes one of the earliest cortical feedforward networks. Despite extensive study, the transformation performed by this network remains poorly understood. We use two-photon calcium imaging to record neural activity in L2-4 of primary vibrissal somatosensory cortex (vS1) as mice perform an object localization task with two whiskers. Touch responses sparsen and become more reliable from L4 to L2, with nearly half of the superficial touch response confined to ~1 % of excitatory neurons. These highly responsive neurons have broad receptive fields and can more accurately decode stimulus features. They participate disproportionately in ensembles, small subnetworks with elevated pairwise correlations. Thus, from L4 to L2, cortex transitions from distributed probabilistic coding to sparse and robust ensemble-based coding, resulting in more efficient and accurate representations.
Topics: Animals; Calcium; Mice; Neurons; Somatosensory Cortex; Touch Perception; Vibrissae
PubMed: 36123376
DOI: 10.1038/s41467-022-33249-1 -
Neuron Nov 2022Rodents explore their environment through coordinated orofacial motor actions, including whisking. Whisking can free-run via an oscillator of inhibitory neurons in the...
Rodents explore their environment through coordinated orofacial motor actions, including whisking. Whisking can free-run via an oscillator of inhibitory neurons in the medulla and can be paced by breathing. Yet, the mechanics of the whisking oscillator and its interaction with breathing remain to be understood. We formulate and solve a hierarchical model of the whisking circuit. The first whisk within a breathing cycle is generated by inhalation, which resets a vibrissa oscillator circuit, while subsequent whisks are derived from the oscillator circuit. Our model posits, consistent with experiment, that there are two subpopulations of oscillator neurons. Stronger connections between the subpopulations support rhythmicity, while connections within each subpopulation induce variable spike timing that enhances the dynamic range of rhythm generation. Calculated cycle-to-cycle changes in whisking are consistent with experiment. Our model provides a computational framework to support longstanding observations of concurrent autonomous and driven rhythmic motor actions that comprise behaviors.
Topics: Animals; Vibrissae; Rodentia; Neurons; Periodicity; Respiration
PubMed: 36113472
DOI: 10.1016/j.neuron.2022.08.020 -
PLoS Computational Biology Sep 2022The rodent vibrissal (whisker) system has been studied for decades as a model of active touch sensing. There are no sensors along the length of a whisker; all sensing...
The rodent vibrissal (whisker) system has been studied for decades as a model of active touch sensing. There are no sensors along the length of a whisker; all sensing occurs at the whisker base. Therefore, a large open question in many neuroscience studies is how an animal could estimate the three-dimensional (3D) location at which a whisker makes contact with an object. In the present work we simulated the shape of a real rat whisker to demonstrate the existence of several unique mappings from triplets of mechanical signals at the whisker base to the three-dimensional whisker-object contact point. We then used high speed video to record whisker deflections as an awake rat whisked against a peg, and used the mechanics resulting from those deflections to extract the contact points along the peg surface. These results demonstrate that measurement of specific mechanical triplets at the base of a biological whisker can enable 3D contact point determination during natural whisking behavior. The approach is viable even though the biological whisker has non-ideal, non-planar curvature, and even given the rat's real-world choices of whisking parameters. Visual intuition for the quality of the approach is provided in a video that shows the contour of the peg gradually emerging during active whisking behavior.
Topics: Animals; Rats; Touch; Touch Perception; Vibrissae; Wakefulness
PubMed: 36108064
DOI: 10.1371/journal.pcbi.1007763 -
Nature Sep 2022Central oscillators are primordial neural circuits that generate and control rhythmic movements. Mechanistic understanding of these circuits requires genetic...
Central oscillators are primordial neural circuits that generate and control rhythmic movements. Mechanistic understanding of these circuits requires genetic identification of the oscillator neurons and their synaptic connections to enable targeted electrophysiological recording and causal manipulation during behaviours. However, such targeting remains a challenge with mammalian systems. Here we delimit the oscillator circuit that drives rhythmic whisking-a motor action that is central to foraging and active sensing in rodents. We found that the whisking oscillator consists of parvalbumin-expressing inhibitory neurons located in the vibrissa intermediate reticular nucleus (vIRt) in the brainstem. vIRt neurons receive descending excitatory inputs and form recurrent inhibitory connections among themselves. Silencing vIRt neurons eliminated rhythmic whisking and resulted in sustained vibrissae protraction. In vivo recording of opto-tagged vIRt neurons in awake mice showed that these cells spike tonically when animals are at rest, and transition to rhythmic bursting at the onset of whisking, suggesting that rhythm generation is probably the result of network dynamics, as opposed to intrinsic cellular properties. Notably, ablating inhibitory synaptic inputs to vIRt neurons quenched their rhythmic bursting, impaired the tonic-to-bursting transition and abolished regular whisking. Thus, the whisking oscillator is an all-inhibitory network and recurrent synaptic inhibition has a key role in its rhythmogenesis.
Topics: Animals; Brain Stem; Mice; Movement; Neural Inhibition; Neural Pathways; Neurons; Parvalbumins; Periodicity; Rest; Synapses; Vibrissae; Wakefulness
PubMed: 36045290
DOI: 10.1038/s41586-022-05144-8 -
International Journal of Molecular... Aug 2022The fibroblast growth factor (FGF) family has various biological functions, including cell growth, tissue regeneration, embryonic development, metabolism, and...
The fibroblast growth factor (FGF) family has various biological functions, including cell growth, tissue regeneration, embryonic development, metabolism, and angiogenesis. In the case of hair growth, several members of the FGF family, such as FGF1 and FGF2, are involved in hair growth, while FGF5 has the opposite effect. In this study, the regulation of the hair growth cycle by FGF12 was investigated. To observe its effect, the expression of FGF12 was downregulated in mice and outer root sheath (ORS) by siRNA transfection, while FGF12 overexpression was carried out using FGF12 adenovirus. For the results, FGF12 was primarily expressed in ORS cells with a high expression during the anagen phase of hair follicles. Knockdown of FGF12 delayed telogen-to-anagen transition in mice and decreased the hair length in vibrissae hair follicles. It also inhibited the proliferation and migration of ORS cells. On the contrary, FGF12 overexpression increased the migration of ORS cells. FGF12-overexpressed ORS cells induced the telogen-to-anagen transition in the animal model. In addition, FGF12 overexpression regulated the expression of PDGF-CC, MDK, and HB-EGF, and treatment of these factors exhibited hair growth promotion. Altogether, FGF12 promoted hair growth by inducing the anagen phase of hair follicles, suggesting the potential for hair loss therapy.
Topics: Animals; Cell Cycle; Fibroblast Growth Factors; Hair; Hair Follicle; Mice; Vibrissae
PubMed: 36012732
DOI: 10.3390/ijms23169467