PIEZO ion channels: force sensors of the interoceptive nervous system.

Many organs are designed to move: the heart pumps each second, the gastrointestinal tract squeezes and churns to digest food, and we contract and relax skeletal muscles to move our bodies. Sensory neurons of the peripheral nervous system detect signals from bodily tissues, including the forces generated by these movements, to control physiology. The processing of these internal signals is called interoception, but this is a broad term that includes a wide variety of both chemical and mechanical sensory processes. Mechanical senses are understudied, but rapid progress has been made in the last decade, thanks in part to the discovery of the mechanosensory PIEZO ion channels (Coste et al., 2010). The role of these mechanosensors within the interoceptive nervous system is the focus of this review. In defining the transduction molecules that govern mechanical interoception, we will have a better grasp of how these signals drive physiology.

Labeling PIEZO2 activity in the peripheral nervous system.

Sensory neurons detect mechanical forces from both the environment and internal organs to regulate physiology. PIEZO2 is a mechanosensory ion channel critical for touch, proprioception, and bladder stretch sensation, yet its broad expression in sensory neurons suggests it has undiscovered physiological roles. To fully understand mechanosensory physiology, we must know where and when PIEZO2-expressing neurons detect force. The fluorescent styryl dye FM 1-43 was previously shown to label sensory neurons. Surprisingly, we find that the vast majority of FM 1-43 somatosensory neuron labeling in mice in vivo is dependent on PIEZO2 activity within the peripheral nerve endings. We illustrate the potential of FM 1-43 by using it to identify novel PIEZO2-expressing urethral neurons that are engaged by urination. These data reveal that FM 1-43 is a functional probe for mechanosensitivity via PIEZO2 activation in vivo and will facilitate the characterization of known and novel mechanosensory processes in multiple organ systems.

Mechanisms of lactic acid gustatory attraction in Drosophila.

Sour has been studied almost exclusively as an aversive taste modality. Yet recent work in Drosophila demonstrates that specific carboxylic acids are attractive at ecologically relevant concentrations. Here, we demonstrate that lactic acid is an appetitive and energetic tastant, which stimulates feeding through activation of sweet gustatory receptor neurons (GRNs). This activation displays distinct, mechanistically separable stimulus onset and removal phases. Ionotropic receptor 25a (IR25a) primarily mediates the onset response, which shows specificity for the lactate anion and drives feeding initiation through proboscis extension. Conversely, sweet gustatory receptors (Gr64a-f) mediate a non-specific removal response to low pH that primarily impacts ingestion. While mutations in either receptor family have marginal impacts on feeding, lactic acid attraction is completely abolished in combined mutants. Thus, specific components of lactic acid are detected through two classes of receptors to activate a single set of sensory neurons in physiologically distinct ways, ultimately leading to robust behavioral attraction.