Summary Innocuous touch of the skin is detected by distinct populations of low-threshold mechanoreceptors (LTMRs), which are classified as Aβ-, Aδ- and C-LTMRs. Here, we report genetic labeling of LTMR subtypes and visualization of their relative patterns of axonal endings in hairy skin and the spinal cord. We found that each of the three major hair follicle types of trunk hairy skin; guard, awl/auchene, and zigzag hairs, is innervated by a unique and invariant combination of LTMRs; thus, each hair follicle type is a functionally distinct mechanosensory end organ. Moreover, the central projections of Aβ-, Aδ- and C-LTMRs that innervate the same or adjacent hair follicles form narrow LTMR columns in the dorsal horn. These findings support a model of mechanosensation in which the activities of Aβ-, Aδ- and C-LTMRs are integrated within dorsal horn LTMR columns and processed into outputs that underlie the perception of myriad touch sensations.

SummaryThe deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception.

The brain is a complex tissue comprising hundreds of distinct cell types, each of which has unique circuitry and plays a discrete role in nervous system function. Large-scale studies mapping gene-expression patterns throughout the nervous system have revealed that many genes are exclusively expressed in specific cell populations. The GENSAT (Gene Expression Nervous System Atlas) Project created a library of engineered mice utilizing bacterial artificial chromosomes (BACs) to drive the expression of enhanced green fluorescent protein (eGFP) in genetically defined cell populations. BACs contain large segments of genomic DNA and retain most of the transcriptional regulatory elements directing the expression of a given gene, resulting in more faithful reproduction of endogenous expression patterns. BAC transgenic mice offer a robust solution to the challenging task of stably and reproducibly accessing specific cell types from a heterogeneous tissue such as the brain. A significant advantage of utilizing eGFP as a reporter is the fact that it can fill entire cells, including neuronal dendrites and axons as well as glial processes, making GENSAT reporter mice a powerful tool for neuroimaging studies. This article provides a primer on the generation of BAC transgenic mice and advantages for their use in labeling genetically defined cell types. It also provides an overview of searching the GENSAT database and ordering engineered mouse lines.