A critical factor that determines whether a given neuron survives or dies during development is its success in accumulating neurotrophic factors of specific kinds, different kinds for different neuronal types (Fig. 24-1). Neurotrophic factors are produced in limited amounts by target tissues (e.g., muscle, glands, other neurons), gobbled up by presynaptic endings, and transported back to the cell body. There they act to prevent apoptosis (programmed cell death) and to promote growth. Going back to the spinal cord example, more dorsal root ganglion cells and motor neurons survive at levels where there’s a lot of target tissue in the periphery (e.g., lower cervical) than at levels where there’s less (e.g., midthoracic). But this isn’t restricted to the spinal cord—throughout the nervous system, something like half of all the neurons produced during development die before birth.

Figure 24-1 Competition for trophic factors and its effects on neuronal survival during development.

Axonal Branches Are Pruned to Match Functional Requirements

Long after neurons finish competing with each other for survival, they continue to compete for neurotrophic factors in an effort to preserve their connections (Fig. 24-2).

Figure 24-2 Competition for trophic factors leading to survival and proliferation of axonal branches during development.

The best-known example is the innervation of skeletal muscle by lower motor neurons. Early on, individual muscle fibers receive inputs from multiple motor neurons. By about the time of birth, all but one input has been pruned away and the sole survivor develops into a single elaborate neuromuscular junction (THB6 Figure 8-11, p. 184). Similar pruning goes on throughout the nervous system; depending on the area involved, this is a process that may continue well after birth.

Pruning of Neuronal Connections Occurs during Critical Periods

Neuronal connections are pruned and refined during limited time windows called critical periods. These are periods during which patterns of connections are fine-tuned, largely completing the process of matching the nervous system to the body and environment; once they end, further change is much more difficult. The downside here is that the decreased plasticity makes it difficult to repair things after damage to adult nervous systems.

The timing of critical periods is roughly correlated with the complexity of neural functions. This makes sense because, for example, multimodal cortical areas can’t finish refining their connections until after unimodal areas are done. Some patterns of connections (e.g., innervation of skeletal muscle) are finalized at birth or earlier. Others (e.g., subtleties of language) continue for another decade or longer (THB6 Figure 24-9, p. 615).

This has important clinical implications: abnormalities in eyes, ears, and social situations early in life need to be avoided or corrected in order to prevent permanent deficits.

Synaptic Connections Are Adjusted throughout Life

Critical periods can’t be the end of the story, though, because changes in synaptic strength continue throughout life. Some of the changes last no more than a few minutes, but others last hours to years, long enough to play key roles in things like learning and memory. Changes in presynaptic or postsynaptic Ca²⁺ concentration play an important part in many, but not all, of these changes.

There Are Short-Term and Long-Term Adjustments of Synaptic Strength

Key Concept

Cortical maps are adjusted throughout life.

Some of the short-term changes in synaptic strength follow naturally from normal synaptic function (Fig. 24-3). A little extra Ca²⁺ hanging around in a presynaptic terminal after transmitter release, for example, can result in potentiation of transmitter release in response to the next action potential. High-frequency stimulation of a presynaptic ending can cause depletion of synaptic vesicles, resulting in depression of subsequent release for a little while. Fast-acting retrograde messengers, such as nitric oxide, can also cause short-term changes.