The brain is the center of the nervous system and the most complex biological structure known. All thoughts, emotions, memories, behaviors, dreams, and other aspects of cognition arise within the brain. The brain coordinates the abilities to move, touch, smell, taste, hear, and see. It enables people to form words, understand mathematics, communicate with others, make decisions, compose and appreciate music, plan ahead, and even fantasize. It comes as no surprise that alterations in brain function account for many, if not most, neurologic and psychiatric disorders.
The human brain consists of more than 1011
(100 billion) neurons, which process and transmit information in the form of electrical signals. Communication between neurons occurs at specialized junctions called synapses. During the past century, basic neuroscience has taught us a great deal about the molecular and cellular mechanisms of synapse formation, stability, and function. Precise control of synaptic development and connectivity is critical for maintaining accurate neuronal network activity and normal brain function. Now it is widely believed that information in the brain can be stored in the form of altered structure and chemistry of synapses and/or by the formation of new synapses and the elimination of old ones [1
]. This so-called plasticity of synapses is believed to be the basis of learning and memory in the brain.
It is not surprising that the inappropriate loss of synaptic stability may lead to the disruption of neuronal circuits and to brain diseases. Whether as the result of genetics, drug use, the aging process, viral infections, or other various causes, dysfunction in neuronal communication is almost certainly the underlying cause of many psychiatric and neurologic diseases, such as mental retardation [2
], schizophrenia [3
], Parkinson’s disease [4
], autism [5
], Alzheimer’s disease (AD) [6
], compulsive behavior [7
], and addiction [8
]. Recent studies show that many neuropsychiatric diseases are characterized by synaptic pathology—including abnormal density and morphology of dendritic spines, synapse loss, and aberrant synaptic signaling and plasticity [9
]. For AD, synaptic loss is the best current pathologic correlate of cognitive decline, and synaptic dysfunction is evident long before synapses and neurons are lost. The synapse thus constitutes an important target for treatments to slow progression and preserve cognitive and functional abilities in the disease. Understanding brain disorders is, at least in part, a matter of understanding the biochemical and cell biological basis of synaptic function and plasticity.
In this review, we discuss recent evidence that alteration in synapse structure and function underlies several psychiatric and neurologic disorders. We describe our current understanding of the molecular organization of excitatory and inhibitory synapses and propose that basic cell biological mechanisms link synapse function with neuropsychiatric health and disease.