IN THE TWO PRECEDING CHAPTERS, we saw how neurons are generated in appropriate numbers, at correct times, and in the right places. These early developmental steps set the stage for later events that direct neurons to form functional connections with target cells. To form connections, neurons have to extend long processes—axons and dendrites—which permit connectivity with postsynaptic cells and synaptic input from other neurons. In this chapter, we examine how neurons elaborate axons and dendrites and how axons are guided to their targets.
We begin the chapter by discussing how certain neuronal processes become axons and others dendrites. We then describe the growing axon, which may have to travel a long distance and ignore many inappropriate neuronal partners before terminating in just the right region and recognizing its correct synaptic targets. We consider the strategies by which the axon overcomes these challenges. Finally, we illustrate general features of axonal guidance by describing the development of two well-studied axonal pathways: one that conveys visual information from the retina to the brain and another that conveys cutaneous sensory information from the spinal cord to the brain.
Differences Between Axons and Dendrites Emerge Early in Development
The processes of neurons vary enormously in their length, thickness, branching pattern, and molecular architecture. Nonetheless, most neuronal processes fit into one of two functional categories: axons and dendrites. More than a century ago, Santiago Ramón y Cajal hypothesized that this distinction underlies the ability of neurons to transmit information in a particular direction, an idea he formalized as the law of dynamic polarization. Cajal wrote that “the transmission of the nerve impulse is always from the dendritic branches and the cell body to the axon.” In the decades before electrophysiological methods were up to the task, this law provided a means of analyzing neural circuits histologically. Although exceptions have been found, Ramón y Cajal’s law remains a basic principle that relates structure to function in the nervous system and highlights the importance of knowing how neurons acquire their polarized form.
Progress in understanding how neuronal polarization occurs comes in large part from studies of neurons taken from the rodent brain and grown in tissue culture. Hippocampal neurons grown in isolation develop processes reminiscent of those seen in vivo: a single, long, cylindrical axon and several shorter, tapered dendrites (Figure 47–1A). As cytoskeletal and synaptic proteins are differentially targeted to these components, axons and dendrites acquire distinctive molecular profiles. For example, a particular form of the Tau protein is localized in axons and the MAP2 protein in dendrites (Figure 47–1B)
The differentiation of axons and dendrites marks the emergence of neuronal polarity.
A. Four stages in the polarization of a hippocampal neuron grown in tissue culture. (Adapted, with permission, from Kaech and Banker 2006. Copyright © 2007 Springer Nature.)
B. Hippocampal neurons grown in culture ...