Synapses and Synaptic Circuits

Neurons are highly specialized for communicating with each other. This communication takes place mostly at a unique anatomical structure: the synapse. Synapses are formed by a presynaptic nerve terminal, which releases chemical neurotransmitter in response to the arrival of an electrical action potential from the axon, the postsynaptic cell, in which neurotransmitter receptors, signaling molecules, and ion channels are concentrated, and the processes of glial cells, which participate in the uptake and metabolism of neurotransmitters and maintain ion homeostasis.

Information is processed in the brain through vast networks of neurons that are specifically wired into synaptic circuits by the synapses among them. As many as 10,000 synaptic inputs from thousands of other neurons converge on a typical neuron and are then integrated by the postsynaptic cell. The results of this integration- action potentials- are then transmitted down the axon to the thousands of cells to which the neuron is synaptically coupled.

Members of the Synapses and Synaptic Circuits focus group are engaged in research devoted to understanding of how individual nerve cells communicate with each other at synapses, and how the behavior of populations of synaptically connected cellssynaptic circuitsis determined by this communication.

Synapses and synaptic circuits in the healthy brain are essential for the functions of learning and memory formation, processing of sensory information, and determination of stereotypical behaviors. There is considerable evidence that several important neurological diseases arise when the elements of certain synapses or synaptic circuits become abnormal or injured, including epilepsy, Alzheimers disease, schizophrenia, chronic pain, mental retardation, and sensory deficits.

Research

Specific areas of interest include: the development and plasticity of synaptic structure, mechanisms of presynaptic transmitter release, properties of postsynaptic receptors, synaptic integration, second messenger signaling pathways, synaptic plasticity, electrophysiological characterization of neuronal cell types, oscillatory activity within neuronal networks, and local circuit interactions. Brain regions of particular interest include the olfactory system, the hippocampal formation, sensory neurons, pain systems, the thalamo-cortical system, the auditory system, and the visual system.

Techniques employed in the pursuit of these studies include: electrophysiological recording from single nerve cells and populations of cells, genetic and pharmacological manipulation of receptor and ion channel expression, neurochemical analysis, cell biological analyses of synaptogenesis, optical imaging with fluorescent labels and indicators, generation and analysis of transgenic mice, photolysis of caged compounds, and anatomical characterization of cells and connections.

Investigators and Extramural Support

The Synapses and Synaptic Circuits focus group consists of more than 50 faculty, postdoctoral fellows, and students within more than 5 academic departments. Numerous close and effective collaborations currently exist between these investigators. Total extramural research funding exceeds $10 million per year. Financial support is provided by grants from many sources, including several different institutes within the National Institutes of Health, as well as other federal and private agencies.

Challenges for the Future

With the full decoding of the human genome, the biggest challenge has shifted to understanding what the function of all those gene products is and how these gene products work together to produce both the complex structure of the nervous system and the delicate web of molecular signals that underlie our impressive cognitive abilities. The members of this focus group are committed to unraveling these mysteries and to minimizing the devastating impact of the many neurological diseases in which synaptic dysfunction has been implicated.

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