The Neuroscientist Comments.

Abstract

Touch is an essential component of life, providing rich and detailed information on our environment that begins with activation of mechanosensitive nerve endings innervating the skin. This information is then conveyed to higher brain centers through the dorsal column nuclei of the brainstem. However, in addition to input directly from low-threshold mechanoreceptors, the dorsal column nuclei also receive signals from postsynaptic dorsal column neurons of the spinal cord, which in turn also integrate mechanoreceptor signals. In their recent study, Turecek and others (2022) sought to investigate the contribution of input from these indirect postsynaptic dorsal column neurons to the coding of touch sensation. By recording from neuron subtypes in the gracile nucleus, in combination with optogenetic tagging and antidromic stimulation, the authors showed that neurons projecting to the ventral posterolateral thalamus responded to low-frequency vibration stimuli and featured small excitatory receptive fields with large regions of surround suppression, suggesting that these neurons convey precise spatial information. In contrast, dorsal column nuclei neurons projecting to the inferior colliculus responded to a large range of vibration frequencies but with large receptive fields, indicative of a larger dynamic range but less discriminative spatial resolution. To determine the contribution of both direct (via Aβ low-threshold mechanoreceptor projections that travel through the dorsal column) and indirect (via postsynaptic dorsal column neurons of the spinal cord) inputs to the responses of dorsal column nuclei neurons, optogenetic silencing through the light-activated chloride channel was used. These experiments revealed that the indirect pathway contributes in particular to responses to very low-frequency mechanical stimulation (10 Hz) but not low-frequency (50 Hz) or high-frequency (300 Hz) vibration. By pharmacologically blocking neurotransmission of postsynaptic dorsal column neurons in the lumbar dorsal horn, a contribution of the indirect pathway to coding of sustained mechanical stimulation, specifically lowto high-intensity skin indentation, was unveiled. Thus, the indirect pathway appears critical for detection and encoding of stimulus intensities, likely through both lowand high-threshold mechanoreceptors (including Aδ and C fiber neurons) that do not project via the direct dorsal column pathway. Using light-induced activation of Calca-expressing highthreshold mechanoreceptors in a Calca-FlpE; Rosa26FSFReaChR mouse line, which exclusively signal via the indirect pathway, as well as stimulation of the direct pathway by vibration, the receptive fields of both dorsal column pathways were found to be highly correlated, suggesting reconvergence of input signals in the dorsal column nuclei to enable precise spatial and intensity representation of mechanical stimuli in single, small receptive fields. Overall, these elegant experiments demonstrate the importance of the indirect postsynaptic dorsal column pathway to brainstem circuits that ultimately allow us to discriminate the location, intensity, and nature of touch.