ABSTRACT

Investigating synapse formation and reorganization in the brain and spinal cord presents many more challenges than those encountered studying the NMJ. As noted in Chapter 9, there are a number of reasons why the NMJ has proven to be an advantageous experimental system. Its relatively large size, experimental accessibility, structural simplicity, and use of a single neurotransmitter system (acetylcholine) are among the characteristics that have made the NMJ useful for studying synaptogenesis. In contrast, CNS synapses generally lack these same features. Typically, CNS synapses are smaller, less accessible, and more difficult to isolate from surrounding cells. In addition, CNS synapses can utilize one or more of the hundreds of different neurotransmitters and neuropeptides that have been identified. The small size and vast number of neurons in the CNS also make it difficult to isolate individual pre-and postsynaptic cells. In addition, one of the largest obstacles to studying specific synaptic connections in the CNS is that each neuronal cell body and dendrite is almost completely covered with nerve terminals from the numerous synaptic partners. Multiple glial cell processes also contact each neuron. The density of innervation was highlighted in a 1969 study of cat spinal motor neurons. In this study, a series of electron micrographs was collected so that the density of innervation on a single motor neuron could be documented (Figure10.1A). This study was one of the first to clearly illustrate the numerous cellular contacts made at a single CNS neuron. In more recent years, fluorescent microscopy has been used to label synaptic elements and document synaptic contacts on CNS neurons under normal and experimental conditions (Figure 10.1B).