Somatosensory system | EPFL Graph Search

In physiology, the somatosensory system is the network of neural structures in the brain and body that produce the perception of touch (haptic perception), as well as temperature (thermoception), body position (proprioception), and pain. It is a subset of the sensory nervous system, which also represents visual, auditory, olfactory, and gustatory stimuli. Somatosensation begins when mechano- and thermosensitive structures in the skin or internal organs sense physical stimuli such as pressure on the skin (see mechanotransduction, nociception). Activation of these structures, or receptors, leads to activation of peripheral sensory neurons that convey signals to the spinal cord as patterns of action potentials. Sensory information is then processed locally in the spinal cord to drive reflexes, and is also conveyed to the brain for conscious perception of touch and proprioception. Note, somatosensory information from the face and head enters the brain through peripheral sensory neurons

From the early steps of whisker formation to its evolutionary disappearance: the (curious) case of Prdm1 and its regulation

Pierluigi Giuseppe Manti

Whiskers (also known as vibrissae) are sensory organs that are thought to have first appeared in Therapsida, a group of synapsids that includes mammals and evolutionary ancestors like the Thrinaxodon(1). They are highly conserved among mammals to the notable exception of the higher primates and are important for behavior, especially for nocturnal animals and the ones living in burrows(2). Furthermore, the mechanoreceptors of the vibrissae signal to the primary somatosensory cortex, where a discrete and well-defined structure in layer 4 represents each whisker(3). This structure, known as barrel cortex, occupies a large portion of the rodent brain. Strikingly, Prdm1 conditional KO (cKO) mice are one of the rare transgenic strains that do not develop whiskers while forming a pelage; on the other hand, the other head structures expressing Prdm1 (including pelage hair follicles and teeth) grow normally(4). In the developing whisker pad, Prdm1 expression is confined to the mesenchyme underlying the embryonic epidermis that will later form the whisker epidermal placode; it lasts until dermal papilla formation, when a âswitchâ occurs to the precursors of the inner root sheath. The Prdm1 ablation study we conducted revealed the absence of the patterned up-regulation of Bmp2 (marker of placode formation), Shh (a protein secreted by the epidermal placode responsible for the first epidermal signal) and Bmp4 (expressed in the pre-follicle mesenchyme). On the other hand, Lef1 is expressed uniformly in the mesenchyme of the whisker pad, thus pointing out the integrity of the Î²Catenin-mediated first mesenchymal signal. Those results suggest the role of Prdm1 as a master gene in whisker development. Prdm1 expressing cells are mainly non-proliferative; however, a small subpopulation at the periphery is cycling. Being Sox2 coexpressed with Prdm1 in the whisker mesenchyme, we performed lineage tracing with Sox2CreERT2 and ROSAYFP transgenic strains. Those experiments revealed that Sox2/Prdm1 expressing cells contribute to the formation of the dermal papilla, dermal sheath and putative pericytes of the whisker follicle and thus constitute a population of embryonic progenitors crucial for whisker formation. We subsequently investigated the development of the barrel cortex in our cKO mice. Intriguingly, a disorganized pattern was observed in cKO mice, suggesting that the loss of expression of a single gene, and consequently the disappearance of vibrissae, drastically impacts the development of the whole somatosensory system. Finally, we hypothesized that the loss of Prdm1 expression might explain the disappearance of whisker follicles in the human during evolution. Prdm1 being no longer expressed in the human lineage during hair follicle development(5), we reasoned that the loss of regulatory elements of its upstream genes might contribute to this phenomenon; we demonstrated that Lef1 acts upstream of Prdm1 during whisker development and are currently testing the role of its potential enhancers (Leaf) during this process. Bibliography: 1: (http://en.wikipedia.org/wiki/therapsid) 2: Petersen, C. C. H. The Functional Organization of the Barrel Cortex. Neuron 56, 339â355 (2007) 3: Woolsey, T. A. & Van der Loos, H. The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectonic units. Brain Res. 17, 205â242 (1970) 4: Robertson, E. J. et al. Blimp1 regulates development of the posterior forelimb, caudal pharyngeal arches, heart and sensory vibrissae in mice. Development 134, 4335â4345 (2007). 5: Sellheyer, K. & Krahl, D. Blimp-1: a marker of terminal differentiation but not of sebocytic progenitor cells. J. Cutan. Pathol. 37, 362â370 (2010).

EPFL2016

Axon regeneration and circuit reorganization after complete spinal cord injury

Sabry Leonardo Barlatey

First human trials involving neuroprosthetic rehabilitation demonstrated recently that significant functional benefits can be achieved with lumbosacral neuromodulation and reorganized spared projections. However, complete spinal cord injuries (SCI) wholly isolate infralesional circuits from any supraspinal control, leading to irreversible motor deficits that neuroprosthetics still fails to address. As axons fail to regrow across the lesion site, neuroregenerative research after SCI has been dogmatically focusing attention on minimizing the environmental inhibitions to axon regeneration. In the present work, we demonstrate that spontaneous axon regeneration failure can be reversed, and that propriospinal axons are able to grow across complete non-neural lesion cores when the required facilitators are provided. We identified three mechanisms needed for propriospinal regrowth : i) enhancing neuronal intrinsic growth capacities using viral technologies, ii) remodeling the lesion core with growth factors, in order to densify permissive substrates, and iii) guiding axons chemically across the SCI site. Propriospinal neurons - that coordinate different spinal segments in healthy conditions - are known to support recovery of locomotion in incomplete models of spinal cord injury. However, restoring a robust descending bridge of propriospinal axons does not by itself promote any functional benefit. We hypothesize that a lack of somatosensory feedback to the motor cortex (M1), together with insufficient descending motor control, may prevent coherent exchange of information between lumbosacral and cortical motor centers. Therefore, we explored the neuroregenerative potential of reticulospinal axons - which are projected from the brainstem to the spinal cord - as a second relay for the descending motor cortical command. Together with axon guidance and lesion remodeling, our viral manipulation of intrinsic growth programs induced limited yet significant reticulospinal regeneration into the lesion core. In order to enhance this reticulospinal regrowth, we explored activity-dependent mechanisms of neurite growth control. As we observed that activity does not recruit growth programs after SCI, we revealed a possible divergence between the mechanisms that underly reticulospinal axon regrowth and neurite sprouting. In the mean time, we are developing a somatosensory interface that aims at restoring sensory feedback to the motor cortex after complete SCI. Based on hindlimb electromyographic activity, we linked locomotion to optogenetic neuromodulation of the motor thalamus, and were able to evoke responses in M1 by selectively activating thalamocortical projections, both before and after complete spinal lesion. Such technology enables a direct recruitment of thalamic nuclei that gate motor learning and motor planning at a cortical level. Coming experiments will test wether a strategy combining propriospinal regeneration with locomotion-dependent thalamocortical modulation is sufficient to restore voluntary stepping after complete SCI.

EPFL2019

Sparse, reliable, and long-term stable representation of periodic whisker deflections in the mouse barrel cortex

Johannes Maria Mayrhofer

The rodent whisker system is a preferred model for studying plasticity in the somatosensory cortex (barrel cortex). Contrarily, only a small amount of research has been conducted to characterize the stability of neuronal population activity in the barrel cortex. We used the mouse whisker system to address the neuronal basis of stable perception in the somatosensory cortex. Cortical representation of periodic whisker deflections was studied in populations of neurons in supragranular layers over extended time periods (up to 3 months) with long-term two-photon Ca2+ imaging in anesthetized mice. We found that inmost of the neurons (87%), Ca2+ responses increased sublinearly with increasing number of contralateral whisker deflections. The imaged population of neurons was activated in a stereotypic way over days and for different deflection rates (pulse frequencies). Thus, pulse frequencies are coded by response strength rather than by distinct neuronal sub-populations. A small population of highly responsive neurons (similar to 3%) was sufficient to decode the whisker stimulus. This conserved functional map, led by a small set of highly responsive neurons, might form the foundation of stable sensory percepts. (C) 2015 Elsevier Inc. All rights reserved.

Academic Press Inc Elsevier Science2015