When the axon of a motor neuron is injured, the neuron loses much of its central afferent connectionns. These central changes are reversed when the axons restore appropriate peripheral contacts. This proposal aims to examine the changing synaptic relationships of injured facial motor neurons following crush injury of the facial nerve in young (3 month) and middle aged (15 month) rats. The model for this analysis is ideal because the facial nucleus is a homogeneous population of motor neurons, its afferent innervation is well characterized, and it loses no neurons with advancing age. Our preliminary studies suggest that recovery of central afferent connections may be incomplete in older animals following peripheral reinnervation. The facial motor nucleus will be examined using morphometry and electron microscope immunocytochemistry to determine the identity of terminals showing GABA-like, serotonin-like and noradrenalin-like immunoreactivity. Standard procedures of fine structure morphometry (including reconstruction from serial thin sections) will establish a """"""""catalog"""""""" of all morphological types of axon boutons in the normal facial nucleus. Following axon crush the response of the identified terminals will be characterized as to their fate and recovery, as will the response of the neurons and neuroglial cells. In addition, autoradiographic analysis will determine the dynamics of loss and recovery of postsynaptic GABA-A, serotonin IA and 2, and Beta- adrenoceptor ligand binding. Receptor dynamics will be correlated with binding to serotonin and noradrenalin uptake sites and presynaptic receptors. These studies will establish a bridge between the results of anatomical, immunocytochemical and pharmacological approaches to the investigation of the effects of advancing age on motor neuron response to injury. Given the crucial role of these synaptic connections and receptors in neuronal excitability and calcium mobilization it is important to understand how advancing age compromises the ability of neurons to recover from peripheral nerve injury. Such understanding is important to the development of therapeutic intervention designed to improve nerve regeneration.
| Vaughan, D W (1994) Effects of peripheral axotomy on presynaptic axon terminals with GABA-like immunoreactivity. Anat Rec 238:248-62 |
