Synapses and Synaptic Circuits
Bradley E. Alger
Thomas Blanpied, Ph.D.
Reha Erzurumlu, Ph.D.
Joseph Kao, Ph.D.
Sergei Karnup, MD, PhD, DSc.
W. Jonathan Lederer, M.D., Ph.D.
Paul W. Luther, Ph.D.
Patricio O'Donnell, M.D., Ph.D.
Elizabeth Powell, Ph.D.
Scott M. Thompson, Ph.D.
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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