Neuroplasticity

Information in the brain is transmitted from neuron to neuron through specialized connections called synapses. A synapse between two neurons is made up of presynaptic and postsynaptic terminals, which are separated by a synaptic cleft. The presynaptic terminal is filled with small vesicles containing chemical neurotransmitters, and the postsynaptic terminal consists of receptors specific for these neurochemicals. Neurons carry information in the form of an electrical impulse called an action potential that is initiated at the cell body and travels down the axon. At the synapse, an action potential causes the voltage-dependent release of neurotransmitter-filled vesicles, thereby converting an electrical impulse into a chemical signal. Neurotransmitters diffuse across the synaptic cleft, where they bind to receptors and generate an electrical signal in the postsynaptic neuron. The postsynaptic cell will then, in turn, fire an action potential if the sum of all its synapses reaches an electrical threshold for firing. Since a neuron can receive synapses from many different presynaptic cells, each cell is able to integrate information from varied sources before passing along the information in the form of an electrical code. The ability of neurons to modify the strength of existing synapses, as well as form new synaptic connections, is called neuroplasticity. It is believed that neuroplasticity may be the underlying cellular mechanism for the brain's ability to encode information during learning. In theory, this is how information is stored as memory.

Defined in this way, neuroplasticity includes changes in strength of mature synaptic connections, as well as the formation and elimination of synapses in adult and developing brains. This encompasses a vast field of research, and similar processes may also occur at peripheral synapses, where much of the pioneering studies on synaptic transmission first took place. In addition, neuroplasticity includes the regrowth (or sprouting) of new synaptic connections following central nervous system injury; following stroke, for example.

The notion that the brain can store information by modifying synaptic connections is not a new one. In fact, Santiago Ramon y Cajal (a founder of modern neuroscience) expressed this theory in 1894, three years before Charles Sherrington coined the term synapse to describe the connections made between neurons. In the late 1940s the neuroplasticity model was advanced by Jerzy Konorski, who used the word plasticity to describe "permanent functional transformations," and Donald Hebb, who ascribed testable physiologic characteristics to synaptic plasticity. However, experimental evidence that synapses are capable of long-lasting changes in synaptic strength did not come until the early 1970s, when Timothy Bliss and Terry Lomo described an increase in the synaptic strength of neurons in the mammalian hippocampus (a region of the brain critical for some forms of memory) following electrical stimulation. They termed this increase long-lasting potentiation, now referred to as long-term potentiation (LTP).

Changes in synaptic strength proved to be bidirectionally modifiable (they increase and decrease in strength) as Serena Dudek and Mark Bear first demonstrated in 1992 by recording activity-driven, long-term depression (LTD) in the hippocampus. The evidence that learning and memory are based on these long-lasting changes in synaptic strength is substantial, but still incomplete. However, defining the molecular constituents in the mechanistic pathway leading from synaptic activity to plasticity continues to strengthen the evidence linking neuroplasticity with learning and memory. In addition, resolving the molecular mechanisms underlying synaptic modification should lead to targets for clinical intervention in eliminating age-related memory loss or synaptic loss following brain damage by enhancing new synaptic connections.