Introduction sphere [5]. The latter experiment showed that immediate

Brain Research 888 2001 267–274 www.elsevier.com locate bres Research report Changes in sensitivity of cholinoceptors and adrenoceptors during transhemispheric cortical reorganisation in rat SmI a , c a,b a Mojtaba Zarei , Vladimir V. Raevsky , Gavin S. Dawe , John D. Stephenson a Department of Neuroscience , Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK b Department of Psychology , Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK c Institute of Higher Nervous Activity and Neurophysiology , Russian Academy of Science, Moscow, Russia Accepted 3 October 2000 Abstract The reorganisation of primary somatosensory cortex that occurs after lesioning the corresponding cortex of the contralateral hemisphere in rat has been termed, ‘transhemispheric cortical reorganisation’. Cholinergic and noradrenergic innervations are hypothesized to be involved in cortical plasticity. The present study investigated the change in responses of somatosensory neurones in the hindpaw representation area to muscarinic cholinoceptor and b-adrenoceptor receptor stimulation, by iontophoretic application of acetylcholine, noradrenaline, propranolol and atropine, during the process of transhemispheric cortical reorganization at 3–4 days and at 20–21 days after lesioning the corresponding area in the contralateral hemisphere. Most neurones in control rats showed excitatory atropine-sensitive responses to acetylcholine, and inhibitory propranolol-sensitive responses to noradrenaline. A marked reduction in neurones exhibiting muscarinic responses from 69 to 22 and b-noradrenoceptor-mediated responses from 62 to 24 were seen in rats 3–4 days post lesion. The proportion of neurones responding had recovered by 3 weeks but the direction of the responses had changed with muscarinic response becoming predominantly inhibitory and b-noradrenoceptor responses predominantly excitatory. It is concluded that trans- hemispheric cortical reorganization involves both receptor types and that the reciprocal changes at different stages after injury maintain cortical plasticity.  2001 Elsevier Science B.V. All rights reserved. Theme : Sensory systems Topic : Somatosensory cortex and thalamocortical relationship Keywords : Reorganization; Plasticity; Acetylcholine; Noradrenaline; Brain damage 1. Introduction sphere [5]. The latter experiment showed that immediate changes do not necessarily last for a long time, suggesting Several studies have described changes in receptive mediation by a different mechanism than that responsible fields in primary somatosensory cortex SmI after deacti- for the long-term reorganisation of cerebral cortex such as vation of the corresponding contralateral cortex. Reorgani- that which occurs after unilateral peripheral nerve damage. sation of receptive fields in the SmI of both flying foxes Recently it has been shown that a unilateral lesion of a and macaque monkeys occurred in contralateral as well as part of SmI results in the reorganisation of contralateral in ipsilateral hemisphere immediately after unilateral in- SmI in rat, a phenomenon termed ‘transhemispheric corti- jection of local anaesthetic into a digit [4]. Cooling of a cal reorganisation’ [28]. The net effect of this reorganisa- small region of the primary somatosensory cortex in the tion is to increase the area of cortex in the intact hemi- same species caused a reversible expansion of receptive sphere serving the body part previously served by the fields in the homologous area of the contralateral hemi- lesioned representation. This is accompanied by a marked increase in the proportion of neurones with bilateral receptive fields. The present paper describes the time Corresponding author. Present address: Rivermead Rehabilitation course and neuromodulatory processes accompanying this Centre, Abingdon Road, Oxford OX3 0LR, United Kingdom. Tel.: phenomenon. This is important because transhemispheric 144-1865-240321; fax: 144-1865-200185. E-mail address : m.zareiiop.kcl.ac.uk M. Zarei. cortical reorganization may contribute to recovery of 0006-8993 01 – see front matter  2001 Elsevier Science B.V. All rights reserved. P I I : S 0 0 0 6 - 8 9 9 3 0 0 0 3 0 7 8 - X 268 M function after brain injury and the adjustments might be buprenorphine Temgesic, 0.05 ml s.c. and allowed to hastened or improved by appropriate pharmacological recover. intervention. The reorganisation of the barrel cortex that occurs in 2.1. Unit recording adult rats after chronic vibrissectomy of all but one whisker, visualised with 2-deoxy glucose [13] was pre- 3–4 days or 20–21 days after lesioning, the rats were 21 vented by locus coeruleus lesions suggesting noradrenergic anaesthetised with urethane 1.0–1.5 g kg i.p. and again involvement in cortical plasticity [22]. Transhemispheric placed in a stereotaxic frame. The skull overlying the left cortical reorganisation also depended on central norad- SmI was removed using a dental drill. The cortex was renergic activity because it was prevented by pretreatment exposed by a narrow slit in the dura and covered with 4 with DSP4, a neurotoxin destroying the noradrenergic agar in saline and core temperature maintained at 37618C innervation of the cortex from the locus coeruleus [28]. using a heating lamp. Five ml of 5 glucose solution in A role for acetylcholine ACh in cortical plasticity is 0.18 NaCl was administered s.c. to offset dehydration. also suggested by the observation that the reorganisation in Single units, isolated by amplitude discrimination, were the somatosensory cortex that would normally occur after recorded from a site contralateral to the centre of the digit removal or sciatic nerve transection was prevented by lesion, defined stereotaxically and confirmed electrophy- depleting cortical ACh with an ipsilateral basal forebrain siologically with cortical evoked potential recording as lesion [12,27]. Sciatic nerve transection also reduced the described previously [28,29], with the central saline-filled response of somatosensory cortical neurones to ion- barrel of a 6-barrelled microelectrode impedance 1–3 MV tophoretic application of ACh suggesting the cortical at 10 KHz, digitised and stored for off-line analysis. reorganisation was associated with changes in cholinocep- Only spontaneously active neurones which responded to tor sensitivity [17]. The present study examined muscarinic iontophoretic application of ACh and NA with muscarinic and b-adrenoceptor responses of somatosensory neurones responses i.e. blocked by atropine and b-adrenoceptor- to iontophoretic application of ACh and noradrenaline mediated responses i.e. blocked by propranolol, respec- NA 3–4 days and 20–21 days after a unilateral cortical tively, were analysed see below. The depth of the lesion, i.e. at early and late stages of transhemispheric electrodes below the pial surface suggested that the cortical reorganisation. neurones from which recordings were made were mostly located in layers IV–V, and this was confirmed by the histological data. 2. Materials and methods 2.2. Microiontophoretic application of drugs