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Clemens, A. M.

Publications and source records attributed to Clemens, A. M..

7 recordsLinked to original sources

A Stickiness Response System in Rats

The perception of stickiness is known to everyone who interacts with the world. While eating, walking, and navigating diverse environments including crowded subways, forests, fields and lunchrooms, stickiness is a common and old sensation. Responses to sticky stimuli have been measured in animal and human brains; however, precise behavioral responses and the underlying neural mechanisms are not well understood. We applied sticky stimuli to three-week-old rat pups and found the effects vary greatly across the animals body: Sticky stimuli are quickly removed from forepaws and nose, but often evoke only little reaction from hindpaws. When we applied sticky (marshmallow, mochi) and non-sticky stimuli (water, oil) to forepaws, we observed stimulus unspecific behaviors (licking and grooming) with variable response onsets as well as three fast-onset sticky-specific behaviors. Sticky-specific behaviors were exclusively triggered by sticky stimuli and included paw shaking and paw swiping (behaviors presumably aiming at stickiness removal) and paw tapping. In tapping, animals gently tap their forepaws onto each other or on the ground; we wondered if the resulting paw-substrate detachments serve stickiness sensing. Blocking of forepaw skin sensation reduced sticky-specific responses to sticky stimuli compared to control conditions (Ringer injections). To assess central representations of stickiness, we obtained in vivo whole-cell recordings of neurons in forepaw-somatosensory-cortex while presenting sticky and non-sticky stimuli to anesthetized rat pups. While responses were heterogeneous across the population, we observed individual neurons that had significantly different responses to stimulus detachment for sticky and non-sticky stimuli. In summary, we describe a fast-onset, body-part-specific stickiness response system in rats, which is strongly driven by forepaw skin afferents.

neuroscience↗

A novel fracture lattice in spiny mouse skin facilitates tissue autotomy and regeneration

Autotomy is a unique phenotype whereby an animal sheds a body part to escape predation1-3. The timing and location of autotomy are tightly regulated by preformed planes of weakness (aka fracture planes) which facilitate tissue loss. While autotomy is often followed by regeneration, these phenotypes are rarely reported in mammals4-9. A notable exception are spiny mice (Acomys) which exhibit skin autotomy and more remarkably, complete tissue regeneration10-14. Presently, mechanisms underlying autotomy and complete regeneration in Acomys skin remain elusive. Here, we report the discovery of a honeycomb-like fracture lattice in Acomys skin whose design directs tissue destruction but also facilitates regenerative healing. Unlike the single continuous surface of a fracture plane, this fracture lattice consists of a three-dimensional array of hexagonal units whose boundaries guide tissue breakage. Moreover, we identify collagen VI as the main constituent of the fracture lattice and find that it is distinctly arranged to initiate fracturing and propagation of skin tearing. By preconditioning the tissue for autotomy, the fracture lattice dampens the damage-induced inflammatory response but also upregulates a pro-regenerative gene signature, accelerating skin appendage regeneration. Lastly, we discovered the key role of spiny hairs in fracture lattice formation, as inhibiting their development leads to abnormal pattern formation and changes in skin fracture mechanics. Our results present a novel example of a uniquely evolved structural adaptation in mammalian skin that links tissue patterning, autotomy and regeneration. We expect that the application of a modular compartment structure to artificial skin and other organ engineering may enhance resilience to injury and facilitate efficient regeneration.

developmental biology↗

Ontogeny of tactile, vocal and kinship dynamics in rat pup huddling

Huddling, a tactile, thermoregulatory and filial social interaction, is a predominant and conserved social interaction mammalian and bird species. The act of huddling is particularly important in early life, when thermoregulation, social touch and bonding are influential for survival and healthy brain and behavioural development. We ask how tactile, vocal and kinship dynamics of rat pup interactions develop. We designed a huddling apparatus where we record and synchronise huddle formation with ultrasonic vocalisation analysis. With development, we see that groups (P6-8 vs older pups) stay longer in triad aggregon (pup huddle) configurations in the huddle trial period. Older pups (P18-20) switch huddle states more often. The spectral characteristics of rat pup vocalisation during huddling task change in development, with a higher peak frequency in P18-20 pups. In all age-groups we observe vocal quieting as aggregons form. We hypothesized that kinship should be a strong determinant of huddling interactions but our findings reveal otherwise. When comparing kin vs non-kin groups we found no differences in aggregon durations or switches. In the youngest age group (P6-8) the amount of USVs were reduced in kin vs non-kin groups, though not in older age groups. To address the role of tactile contact in quieting we integrated touch dividers in the huddle arena. Without touch, we saw that vocalisations significantly increased in P6-8 and P11-14, but not in P18-20 kin sibling groups. We suggest that rat pups have a strong internal drive towards huddling behaviour regardless of whether huddle partners are related by kinship. USV analysis suggests that huddling has a calming effect, where related sibling young pups show less distress overall; absence of touch is associated with increased distress in P6-8 and P11-14 kin huddle groups. Thus, huddling is a natural social behaviour that is intrinsically rewarding and shared between both related siblings and unrelated conspecifics; it has calming effects - as indicated by USVs - that depend on kinship and tactile contact during the earliest stages of development.

neuroscience↗

Tactile Mechanisms and Afferents Underlying the Rat Pup Transport Response

Juvenile rodents and other altricial mammals react with calming, immobility and folding up of feet to parental pickup, a set of behaviors referred to as transport response. Here we investigate sensory mechanisms underlying the rat transport response. Grasping rat pups in anterior neck positions evokes strong immobility and folding up of feet, whereas more posterior grasping positions have lesser effects on immobility and foot position. Transport responses are enhanced by slow (1Hz) and even more so by fast (4Hz) gentle shaking and translation of the pup, features consistent with parental transport. In response to lateral grasping, the forepaw below the grasping position points downwards and the forepaw lateral to the grasping position points upwards and medially. Such forepaw adjustments put the pups center of gravity below the grasping point, optimizing pup transportability along with folding up of feet and tail lifting. Tactile stimuli on the back, belly, tail, whisker, dorsal forepaws and dorsal hind-paws do not significantly affect the behaviour of anterior-neck-held pups. Instead, ground contact or paw stimulation consistent with ground contact disrupts transport responses. We identify afferents mediating the transport response by examining membrane labelling with FM1-43 following anterior neck grasping. We observe a dense innervation of the anterior neck skin region ([~]30 terminals/ mm2). We also observed an age-related decrease of cytochrome oxidase reactivity in the rat somatosensory cortical neck representation, a possible correlate to the developmental decrease in the pup transport response. We conclude anterior neck grasping and loss of ground contact trigger calming and postural adjustments for parental transport in rat pups, responses putatively driven from the densely innervated anterior neck skin.

neuroscience↗

Rat Wetness Response: Sensory Cues, Behavior & Fur-based Drying

It never rains in standard lab-confinements; thus we have limited understanding of animal reactions to water and wetness. To address this issue, we sprayed water on different body parts of rats and measured drying and fur temperature by thermal imaging while manipulating behavior, sensory cues and fur. Spraying water on rats resulted in fur changes (hair clumping, apex formation), grooming, shaking, and scratching. Anesthesia abolished behavioral responses, interfered with fur changes, and slowed drying. Spraying water on different body parts resulted in differential behavioral drying responses. Spraying the head resulted in grooming and shaking responses; water evaporated twice as fast as water sprayed on the animals back or belly. We observed no effect of whisker removal on post-water-spraying behavior. In contrast, local anesthesia of dorsal facial skin reduced post-water-spraying behavioral responses. Shaving of head fur drastically enhanced post-water-spraying behaviors, but reduced water loss during drying; indicating that fur promotes evaporation, acting in tandem with behavior to mediate drying. Excised wet fur patches dried and cooled faster than shaved excised wet skin. Water was sucked into distal hair tips, where it evaporated. We propose the wet-fur-heat-pump-hypothesis; fur might extract heat required for drying by cooling ambient air. O_FIG O_LINKSMALLFIG WIDTH=186 HEIGHT=200 SRC="FIGDIR/small/557175v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@ea8b80org.highwire.dtl.DTLVardef@6ca3d9org.highwire.dtl.DTLVardef@78fccdorg.highwire.dtl.DTLVardef@11d0c83_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Supraorbital whiskers act as wind-antennae in rat anemotaxis

We know little about mammalian anemotaxis, wind-sensing. Recently, however, Hartmann and colleagues showed whisker-based anemotaxis in rats. To investigate how whiskers sense airflow, we tracked whisker tips in anesthetized or cadaver rats under no airflow, low airflow and high (fan-blowing) airflow. Whisker tips showed little movement under no airflow conditions and all whisker tips moved during high airflow. Low airflow conditions - most similar to naturally occurring wind stimuli - engaged whisker tips differentially. Most whiskers moved little, the long supraorbital whisker showed maximal displacement and , A1, {beta}, and {gamma} whiskers also showed movements. The long supraorbital whisker differs from other whiskers in its exposed dorsal position, upward bending, length and thin diameter. Ex vivo extracted long supraorbital whiskers also showed exceptional airflow displacement, suggesting whisker-intrinsic biomechanics mediate the unique airflow-sensitivity. Micro computed tomography revealed that the ring-wulst - the follicle structure receiving the most sensitive afferents - was more complete/ closed in supraorbital and other wind-sensitive whiskers than in non-wind-sensitive whiskers, suggesting specialization of the supraorbital for omni-directional sensing. We localized and targeted the cortical supraorbital whisker representation in simultaneous Neuropixels recordings with D/E-row whisker barrels. Responses to wind-stimuli were stronger in the supraorbital 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 supraorbital whisker follicles also diminished airflow turning responses compared to control injections. We conclude that supraorbital whiskers act as wind antennae. New and NoteworthyAnimals rely on sensory processing of airflow (anemotaxis) to guide navigation and survival. We examined mechanisms of rat anemotaxis by combining whisker tracking, biomechanical analysis, micro computed tomography of follicle structure, Neuropixels recordings in the barrel field, behavior of airflow turning and whisker interference by trimming and lidocaine injections. This diversity of methods led to a coherent pattern of results. Whiskers greatly differ in their airflow sensitivity and strongly wind-responsive whiskers - in particular long supraorbital whiskers - determine behavioral responses to airflow stimuli in rats.

neuroscience↗

Estrus-Cycle Regulation of Cortical Inhibition

Female mammals experience cyclical changes in sexual receptivity known as the estrus-cycle. Little is known about how estrus affects the cortex although alterations in sensation, cognition and the cyclic occurrence of epilepsy suggest brain-wide processing changes. We performed in vivo juxtacellular and whole-cell recordings in somatosensory cortex of female rats and found that the estrus-cycle potently altered cortical inhibition. Fast-spiking interneurons strongly varied their activity with the estrus-cycle and estradiol in ovariectomized females, while regular-spiking excitatory neurons did not change. In vivo whole-cell recordings revealed a varying excitation-to-inhibition-ratio with estrus. In situ hybridization for estrogen receptor {beta} (Esr2) showed co-localization with parvalbumin-positive interneurons in deep cortical layers, mirroring the laminar distribution of our physiological findings. In vivo and in vitro experiments confirmed that estrogen acts locally to increase fast-spiking interneuron excitability through an estrogen receptor {beta} mechanism. We conclude that sex hormones powerfully modulate cortical inhibition in the female brain.

neuroscience↗