Partial denervation of the whiskerpad in adult mice: pattern and origin of reinnervation Marc-Etienne Corthe Âsy, Gilles Bronchti and Egbert Welker Institut de Biologie Cellulaire et de Morphologie, University of Lausanne, rue du Bugnon, 9, 1005 Lausanne, Switzerland Keywords: adult plasticity, nerve regeneration, peripheral nerves, somatosensory system, whisker follicle Abstract We studied sensory organ reinnervation after nerve transection in the mouse whisker-to-barrel pathway. In one set of adult mice, we determined at light microscopy level the number of ®bres reaching the caudal whisker follicles 5, 15, 20, 60, 100 days and 1 year after transection of the sensory nerve of row C. Regenerated ®bres were ®rst detected 15 days post lesionem (p.l.) and myelin ®rst observed at 20 days. Between 60 and 100 days, the number of ®bres stayed at » 80% of the values obtained in control animals. At that time, myelinated ®bres reached only 58% of their number in controls. At the electron microscopy level, these ®bres differ from control ones by a smaller ®bre diameter. The innervation of follicles of adjacent rows was not modi®ed, indicating that follicular reinnervation is row speci®c. We checked this feature by injecting in another set of mice the denervated follicles and the adjacent ones with distinct retrograde tracers 45 days and 1 year after nerve transection. The percentage of double-labelled neurons in the Gasserian ganglion did not increase in experimental animals. This con®rms the absence of colonization of intact follicles by regenerating ®bres and indicates that reinnervation of the whisker follicles takes place by regeneration of the degenerated axons without collateral reinnervation. The companion paper describes the pattern of activation of the barrel cortex relative to the present ®ndings. Introduction Transection of a peripheral nerve in adult mammals triggers a series of events leading on one hand to reinnervation of the peripheral target and on the other to functional modi®cations in the central sensory stations. Historically, partial peripheral sensory denervation in various animal models allowed the description of important plastic features of the adult mammalian brain (Merzenich et al., 1983). The phenomena occurring in the sensory periphery were less studied in this context, although interpretation of deafferentation experiments would bene®t from a precise description of the pattern of reinnerva- tion of the peripheral target(s). In a lesioned peripheral nerve, the distal stump and a segment of the proximal stump degenerate (for a review, see Sunderland, 1991). The axons then start regrowing by forming several sprouts, some of which cross the lesion site to reach a peripheral target. The peripheral reconnections can be such that the sprouts from axotomized ganglionic cells can reach their original target or a different one, or even both (Terzis & Dykes, 1980). Besides, intact nerve ®bres in the neighbourhood of a denervated target can also show sprouting, contributing to reinnervation of the denervated target ± a phenomenon named `collateral sprouting' (Diamond et al., 1976). Another factor that modi®es the pattern of innervation of a sensory organ after regeneration is due to collaterals of the regenerated axons innervating a foreign, intact target (Kinnman et al., 1992). In the central nervous system, functional changes take place at the cortical and subcortical levels upon partial peripheral sensory deprivation [for a review, see Kaas (1991) and, in this issue, Bronchti et al., (1999)]. The functional maps generally shift in such a way that central neurons formerly activated by stimulation of the denervated peripheral territory become activated by stimulation of territories adjacent to it. As these plastic changes could not be observed in a somatosensory cortex previously deprived of its cholinergic innerva- tion (Juliano et al., 1991; Webster et al., 1991), it is understood that a central mechanism underlies the plasticity observed in the cortical sensory maps. The aim of this study is to understand the role of the periphery in the modi®cation of the activation observed in the somatosensory stations upon stimulation of the reinnervated sensory organ. In a complementary study referred to as `the companion paper', we have studied the cortical reorganization by measuring the cortical uptake of 2-deoxyglucose upon stimulation of the denervated whiskers, or whiskers adjacent to the denervated ones, 100 days after nerve transection. We used the mouse whisker-to-barrel pathway in this context because the functional modi®cations taking place along this pathway stand out against anatomical maps of the periphery that are easily revealed in most of the somatosensory stations (Woolsey & Van der Loos, 1970; Van der Loos, 1976; Belford & Killackey, 1979; Arvidsson, 1982). The whiskers follicles are densely innervated sensory organs arranged in ®ve rows, A±E, that are bordered posteriorly by four straddlers, a to d. Sensory follicular nerves (one from each follicle) gather into row nerves which merge caudally into the infraorbital nerve, a branch of the trigeminal nerve (Do Èr¯, 1985). The sensory innervation of the whisker follicles follows a double (caudo-rostral and dorso-ventral) gradient of density with d being innervated by the highest number of ®bres and A4 by the smallest number (Welker & Van der Loos, 1986). Previous studies have shown that after partial peripheral deprivation, the functional Correspondence: Professor Egbert Welker, as above. E-mail: egbert.welker@ibcm.unil.ch Received 10 September 1998, revised 1 April 1999, accepted 7 April 1999 European Journal of Neuroscience, Vol. 11, pp. 2835±2846, 1999 ã European Neuroscience Association