Muscarinic receptors in the central nervous system of the rat. IV. A comparison of the effects of axotomy and deafferentation on the binding of [3H]propylbenzilylcholine mustard and associated synaptic changes in the hypoglossal and pontine nuclei.

The reaction of axotomy has been studied in the rat hypoglossal nucleus by quantitative electron microscopical counts of numbers of synapses and by changes in muscarinic receptors assessed by counting silver grains in light microscope autoradiographs of the specific (atropine-sensitive) binding of [3H]propylbenzilylcholine mustard in cryostat sections. For the first 5 days after unilateral peripheral hypoglossal nerve axotomy the muscarinic ligand binding falls to 50% of control levels and then shows no further fall for up to 30 days. Synapse numbers decrease progressively over the first 10 days after operation, by which time they reach 50% of normal. Thus receptor changes reach completion at a time when synapse loss is still continuing. Later, both muscarinic ligand binding and synapse numbers recover to an extent which depends at least in part on the effectiveness of the peripheral nerve regeneration, suggesting that both the receptor and synapse changes may be dependent upon neuromuscular contacts. The reactions of muscarinic receptors to axotomy and deafferentation have been studied in the rat basilar pontine nuclei. Cerebellectomy, which causes axotomy of the pontine neurones and also removes their postsynaptic targets (the granule cells), causes no change in pontine muscarinic receptor over the first week after operation. This differs from the rapid fall in hypoglossal muscarinic receptors induced by axotomy. At longer survivals after cerebellectomy there is a partial loss of pontine muscarinic receptors associated with atrophy of the pontine neurones. Destruction of the neocortical afferents causes a loss of at least half of the synapses in the pontine neuropil. However, the light microscopic autoradiographic study revealed no obvious changes in the dentisy or distribution of the pontine muscarinic receptors from 4 days to more than 6 months after operation.