Plasticity of Glutamate Synaptic Mechanisms

Abstract Epilepsy may be defined as a disorder of brain function characterized by the repeated and unpredictable occurrence of seizures. Seizures involve the disordered, rhythmic, and synchronous firing of central nervous system (CNS) neuron populations. Seizures originate in neuronal populations capable of bursting, develop because of an imbalance between neuronal excitation and inhibition, and are characterized by high-frequency firing associated with membrane depolarization. Neuronal excitation and inhibition may become unbalanced in many different ways. This chapter focuses on the contribution to seizures of glutamate synaptic plasticity, both anatomical plasticity that creates new excitatory synapses and functional plasticity that enhances the efficacy either of excitatory synapses or of glutamate itself. Observations made with human tissue are emphasized. Glutamate is the principal excitatory neurotransmitter in mammals. About 60%–70% of all synapses in the CNS appear to be glutamate synapses (see Fig. 12–1). Glutamate also serves as the principal neurotransmitter utilized by sensory neurons. Autonomic neurons and motoneurons are about the only excitatory neurons in mammals that utilize a transmitter other than glutamate. Thus, the formation of enhanced or novel glutamate circuits, enhanced excitatory transmission, and/or an excess of glutamate itself could disrupt the balance of excitation and inhibition leading to the occurrence of seizures.