Maturation of cutaneous sensory neurons from normal and NGF-overexpressingmice

In the rodent, cutaneous sensory neurons mature over the first two postnata l weeks, both in terms of their electrical properties and their responses t o mechanical stimulation of the skin. To examine the coincidence of these e vents, intracellular recordings were made from neurons in the dorsal root g anglion (DRG) in an in vitro spinal cord, DRG, and skin preparation from mi ce between the ages of postnatal day 0 and 5 (P0-P5). We also examined mice in which nerve growth factor (NGF) is overexpressed in the skin. NGF has b een shown to be involved in a number of aspects of sensory neuron developme nt and function. Therefore we ask here whether excess target-derived NGF wi ll alter the normal course of development, either of somal membrane propert ies, physiological response properties, or neuropeptide content, In wad-typ e mice, somal action potentials (APs) were heterogeneous, with some having simple, uninflected falling phases and some displaying an inflection or bre ak on the falling limb. The proportion of neurons lacking an inflection inc reased with increasing age, as did mean conduction velocity. A variety of r apidly and slowly adapting responses could be obtained by gently probing th e skin; however, due to relatively low thresholds and firing frequencies, a s well as lack of mature peripheral receptors such as hairs, it was not pos sible to place afferents into the same categories as in the adult. No corre lation was seen between the presence or absence of an inflection on the som al AP (a marker for high-threshold mechanoreceptors in adult animals) and e ither peripheral threshold or calcitonin-gene related peptide (CGRP) conten t. Small differences in the duration and amplitude of the somal AP were see n in the NGF-overexpressing mice that disappeared by P3-P5. Excess target-d erived NGF did not alter physiological response properties or the types of neurons containing CGRP. The changes that did occur, including a loss of th e normal relationship between AP duration and conduction velocity, and a de crease in mean conduction velocity in the inflected population, might best be explained by an increase in the relative proportions of myelinated nocic eptors. Of greatest interest was the finding that in both NGF overexpresser s and wild-type mice, the correlation between mechanical threshold and pres ence or absence of an inflection on the somal spike is not apparent by P5.