The skinny on touch: central representations of hairy and glabrous (hairless) skin
In Chapter 6 of Principles of Neurobiology, we learned about how the nervous system collects sensory information of various modalities at its periphery and transmits this information into the CNS, processing it en route. Each sensory system allocates more neural resources to detecting, processing, and transmitting information deemed more important to an organism’s survival and reproduction than other information. For example, the primate retina allocates an overwhelming fraction of its color-detecting cone photoreceptors to the fovea (Section 4.8) to represent color in the center, rather than the periphery, of the organism’s visual field; likewise, foveal color vision consistently occupies more neural “real estate” in higher visual areas (Section 4.20).
Another well-known example of biased central sensory representation is the somatosensory homunculus, a map of the portions of the somatosensory cortex devoted to sensing different skin surfaces (Section 1.11; Figure 1-25). The human somatosensory cortex disproportionately represents high tactile acuity hairless (or “glabrous”) regions such as the lips and fingertips, yet it is unclear where in the somatosensory system such representational biases emerge. Are there simply more primary sensory dorsal root ganglion (DRG) neurons representing the higher acuity skin surfaces, leading to greater central representation of these surfaces? Put simply, where in the nervous system does the mammalian somatosensory “homunculus” attain its beautifully grotesque form?
To address these questions, Lehnert and Santiago et al. (2021) utilized a combination of complex mouse genetic tools, sophisticated physiological preparations, and sparse anatomical reconstructions. Initial physiological mapping of responses of higher somatosensory brain areas and somatosensory brainstem neurons to stroking of hairy and glabrous skin revealed disproportionate representation of glabrous skin, such as a mouse’s paw pads, suggesting that the mammalian somatosensory homunculus might first emerge in the brainstem, which projects to higher somatosensory areas (Section 6.31, Figure 6-71). This hypothesis was supported by in vivo 2-photon imaging of projection neurons within the brainstem.
What causes these biased representations in the somatosensory brainstem? One possibility is that each glabrous skin-targeting DRG neuron might somehow provide more and/or stronger inputs to the brainstem than their hairy skin-targeting counterparts. Axonal arbor reconstructions and quantification of synaptic markers of sparsely-labeled DRG neurons targeting either glabrous or hairy skin revealed that glabrous skin-targeting DRG neurons had larger arbors and more synapses per neuron in the brainstem, suggesting a mechanism for their physiological over-representation in the brainstem. These results were corroborated by physiological recordings of brainstem neurons responding to optical stimulation of hindlimbs designed to mimic sensory stimuli and tuned to induce single DRG neuron spikes: glabrous skin-originating DRG neuron single spikes induced larger postsynaptic currents and generated a higher chance of postsynaptic brainstem neuron spiking than their hairy skin-originating counterparts, providing a physiological correlate to the anatomical findings. Together, these data suggest a model wherein brainstem neurons receiving signals from glabrous skin-projecting light touch DRG neurons integrate inputs from fewer (but stronger) presynaptic neurons, producing a “synaptic expansion” that patterns body representation in the brain.
Thus, single glabrous skin-innervating DRG axons arborize more, create more synapses, and provide more physiological input, causing more postsynaptic spiking, than single hairy skin-innervating DRG axons. What molecular mechanisms regulate the establishment of these biased circuits? Since activity helps wire up other developing sensory systems (Chapters 5, 7), the authors asked whether disrupting gentle touch would impact the formation of this glabrous skin-biased pre-homuncular somatosensory circuitry. To do so, they deleted Piezo2, the mechanosensitive ion channel responsible for gentle touch (Section 6.28), in DRG neurons and reprised their unitary optical stimulation-mapping protocol. Surprisingly, no changes were detected in mice lacking Piezo2, suggesting that mechanosensory stimulus-evoked activity is not required for establishment of the somatosensory brainstem homunculus.
Together, these findings constitute an unprecedented physiological and anatomical mapping of the development of light touch circuitry from primary sensory neurons to cortex and reveal how the somatosensory homunculus emerges at the synapse between DRG light touch neurons and their direct targets in the somatosensory brainstem. These findings also raise several burning questions: 1) How does the skin type a DRG neuron innervates regulate its central arborization—do different skin types attract neurons already preprogrammed to arborize differentially, or does skin type provide a cue that instructs central arborization (Fig. 7G)? 2) In many sensory systems, spontaneous as well as sensory-evoked activity is important for circuit wiring (Section 5.10, 5.11); as Piezo2 deletion does not appear to alter light touch circuitry, does spontaneous activity instead play a role in wiring up these circuits? 3) This study focused on light touch-sensing circuitry: do similar homunculi apply for non-light touch somatosensory modalities such as temperature sensing and noxious mechanical stimuli? If so, where do they emerge? 4) Why is hairy skin touch so strongly represented in early postnatal development and then so dramatically downregulated? 5) Finally, how is the touch umwelt—the organism’s tactile world—represented in other creatures, ranging from non-hairy mammals (e.g. cetaceans) to those from distant clades with well-developed central somatosensory circuitry (e.g. birds, reptiles)? The answers to these questions—and many fascinating others—await our exploration…
Schematic illustrating expansion of glabrous skin representation in the somatosensory brainstem and potential developmental mechanisms. Figure adapted from Lehnert et al., 2021. See Lehnert et al., 2021 for more details.
Figure 7
Schematic illustrating expansion of glabrous skin representation in the somatosensory brainstem and potential developmental mechanisms. Figure adapted from Lehnert et al., 2021. See Lehnert et al., 2021 for more details.
Reference
Lehnert, B. P., Santiago, C., Huey, E. L., Emanuel, A. J., Renauld, S., Africawala, N., ... & Ginty, D. D. (2021). Mechanoreceptor synapses in the brainstem shape the central representation of touch. Link