Professor of Neuroscience
March 3, 2003
Synaptic Plasticity The Brain's Response to Experience
One of the most fascinating and important properties of the mammalian brain is its plasticity. Plasticity refers to the ability of experience, whether it be learning in a classroom, a stressful event, or ingestion of a drug, to modify the organization and behavior of neural circuits in the brain. Experience- dependent brain plasticity is in large part due to long-lasting, activity- dependent changes in the strength of communication at excitatory synapses, that is synaptic plasticity.
The most well-understood forms of synaptic plasticity are termed long- term potentiation (LTP) and long-term depression (LTD) and these have been studied most extensively in the hippocampus, a region of the brain known to be important for a number of different forms of learning and memory. LTP, which refers to a long- lasting increase in synaptic strength, and LTD, which refers to a long- lasting decrease in synaptic strength, are triggered by different patterns of neural activity that lead to the activation of a specific subtype of receptor for the neurotransmitter glutamate, termed an NMDA receptor. When activated, the NMDA receptor lets calcium enter the cell and depending on the detailed characteristics of this calcium signal, different intracellular signaling cascades are activated leading to LTP or LTD. Specifically LTP involves activation of specialized enzymes (termed protein kinases) while LTD involves activation of enzymes (termed protein phosphatases). These enzymes then modify a different family of glutamate receptors (termed AMPA receptors) and it is this modification of AMPA receptors that directly leads to LTP or LTD. Indeed, LTP and LTD may be the first steps leading to structural changes in the brain, specifically the formation of new synaptic connections (LTP) or the elimination of pre-existing synaptic contacts (LTD).
How do we know LTP and LTD are really important for brain plasticity? Work from a number of laboratories has shown that drugs or genetic manipulations that prevent LTP and/ or LTD also routinely impair many different forms of learning and memory. Indeed, these forms of synaptic plasticity may also play an important role in certain disease states. For example, drugs of abuse such as cocaine modify the strength of excitatory synapses in certain key brain regions known to be involved in addiction. Thus in addition to being important for adaptive forms of experience-dependent plasticity, synaptic plasticity may also play an important role in the etiology of pathological behaviors such as addiction.