Chapter 18- Receptors of the Somatosensory System

Explain how dorsal root ganglion neurons differ in size, gene expression, and skin innervation patterns
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DRG neurons differ in the size of their cell soma, gene expression profile, conduction velocity of their axons, sensory transduction molecule(s), innervation pattern in the body, and physiological function.

For example, DRGs that innervate mechanoreceptors that sense touch and proprioception have the largest cell bodies and large myelinated axons; they express proteins such as Npy2r or parvalbumin (PV).

In contrast, DRG neurons that sense temperature or irritant chemicals have small cell bodies and unmyelinated axons; they express calcitonin gene-related peptide (CGRP) or the lectin IB4. As these fluorescent molecular labels extend through the axons to their peripheral endings in the body and in the central nervous system, David Ginty and colleagues were able to characterize the pattern of somatosensory nerve endings in the body and trace their central projections to the spinal cord and brain stem.
Electrical stimuli of increasing strength evoke action potentials first in the largest axons, because they have the lowest electrical resistance, and then progressively in smaller axons. Large-diameter fibers conduct action potentials more rapidly because the internal resistance to current flow along the axon is low, and the nodes of Ranvier are widely spaced along its length. The conduction velocity of large myelinated fibers (in meters per second) is approximately six times the axon diameter (in micrometers), whereas thinly myelinated fibers conduct at five times the axon diameter. For unmyelinated fibers, the factor for converting axon diameter to conduction velocity is 1.5 to 2.5.

Electrical stimulation of a peripheral nerve at varying intensities activates different types of nerve fibers. The action potentials of all the nerves stimulated by a particular amount of current are summed to create the compound action potential. The distinct conduction velocities of different classes of sensory and motor axons produce multiple peaks
(Drawing figure may help on this one)

TRP channels consist of membrane proteins with six transmembrane α-helices. A pore is formed between the fifth (S5) and sixth (S6) helices from the four subunits. Most of these receptors contain ankyrin repeats in the N-terminal domains and a common 25-amino acid motif adjacent to S6 in the C-terminal domain. Individual TRP channels are composed of four identical TRP proteins. All TRP channels are gated by temperature and various chemical ligands, but different types respond to different temperature ranges and have different activation thresholds. At least six types of TRP receptors have been identified in sensory neurons; the thermal sensitivity of a neuron is determined by the particular TRP receptors expressed in its nerve terminals. At 32°C (90°F), the resting skin temperature (asterisk), only TRPV4 and some TRPV3 receptors are stimulated. TRPA1and TRPM8 receptors are activated by cooling and cold stimuli. TRPM8 receptors also respond to menthol and various mints; TRPA1 receptors respond to allium expressing plants such as garlic and radishes. TRPV3 receptors are activated by warm stimuli and also bind camphor. TRPV1 and TRPV2 receptors respond to heat and produce burning pain sensations. TRPV1 channels also respond to a variety of substances, temperatures, or forces that can elicit pain. Their sites of action on the receptor include binding sites for chili peppers' active ingredient (capsaicin), acids (lemon juice), spider venoms, and phosphorylation sites for second messenger activated kinases. TRPV4 receptors are active at normal skin temperatures and respond to touch.
Each spinal or cranial nerve receives sensory inputs from a particular region of the body called a dermatome; the muscles innervated by motor fibers in the corresponding peripheral nerve constitute a myotome. These are the skin and muscle regions affected by damage to peripheral nerves. Because the dermatomes overlap, three adjacent spinal nerves often have to be blocked to anesthetize a particular area of skin. The distribution of spinal nerves in the body forms the anatomical basis of the topographic maps of sensory receptors in the brain that underlie our ability to localize specific sensations.
Describe the process of touch and pain fiber projections to the spinal cord dorsal horn*Draw figure out then describe...* The spinal gray matter in the dorsal horn and intermediate zone of the spinal cord is divided into six layers of cells (laminae I-VI), each with functionally distinct populations of neurons. Neurons in the marginal zone (lamina I) and in lamina II receive nociceptive or thermal inputs from receptors innervated by Aδ or C fibers. The zone for inputs from low-threshold mechanoreceptors (LTMR) is located below lamina II and spans laminae III to V, with the smallest fibers (C-LTMRs) located dorsally, and the largest fibers (Aβ LTMRs) terminating ventrally. LTMRs innervating a particular patch of skin are aligned to form a narrow cell column in the spinal dorsal horn, terminating on spinal interneurons or on projection neurons that send their axons to the brain stem. The medial-lateral arrangement of spinal nerves in the dorsal horn provides a somatotopic representation of adjacent skin areas in the body. The spinal nerve projections of Aβ LTMRs extend to multiple spinal segments along the rostrocaudal axis, whereas those of Aδ or C fibers are more localized to the immediate entry segment (not shown). Aβ LTMRs also send branches to the dorsal column nuclei in the brain stem (Chapters 19 and 20).