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Distributed
properties of synaptic plasticity in simple neural circuits. An
individual neuron in the brain is not able to process information in isolation
from other neurons in the local network, but the precise interconnections and
interactions with neighboring neurons confer the ability to the brain to see,
to learn, to think, to remember. Activity-dependent changes, or plasticity, of
the strength of neuronal signaling play a critical role in shaping developing
neural circuits as well as modifying information transmitted and encoded in existing
neuronal connections. Indeed, it is generally agreed that memories or information
are stored in activity-dependent modifications in synaptic efficacy. However,
the cellular and molecular mechanisms underlying used-dependent changes in synaptic
efficacy remain ill-defined. The research in my laboratory is aimed at establishing
a functional definition for synaptic connectivity, and determining the relationship
between morphological changes in pre- and postsynaptic structures and functional
synaptic transmission during development and plasticity. Multiple simultaneous
patch-clamp recordings from identified microcircuits of neurons in culture and
brain slice allow examination of mechanisms underlying activity-dependent changes
in synaptic efficacy. Time-lapse video microscopy of cells expressing fluorescent
fusion proteins labeling essential components of neuronal signaling allows us
to study dynamics of neurons during synaptogenesis and plasticity. An understanding
of the fundamental principles governing activity-dependent synaptic and circuit
modifications will provide insights into the development and organization of the
nervous system. 
Figure caption:
A phase-contrast microscopic image of a triplet network in a 10-day old hippocampal culture, together with three pipettes used for whole-cell perforated patch recording.
Recent
publications:
Chen,
Y., Bourne, J., Pieribone, V.A., Fitzsimonds, R.M. (2004) The
role of actin in the regulation of dendritic spine morphology and bidirectional
synaptic plasticity. Neuroreport, 15(5):829-32. Krueger,
S., Kolar, A., Fitzsimonds, R.M. (2003) The
presynaptic release apparatus is functional in the absence of dendritic contact
and highly mobile within isolated axons. Neuron, 40:945-57. Moresco,
E.M., Scheetz, A.J., Bornmann, W.G.,Koleske, A.J., Fitzsimonds, R.M. (2003) Abl
family non-receptor tyrosine kinases modulate short-term synaptic plasticity.
J. Neurophysiol., 89(3):1678-87 Fitzsimonds
RM, Poo MM. Retrograde
signaling in the development and modification of synapses. Physiol Rev. 1998
Jan;78(1):143-70.
Fitzsimonds RM, Song HJ, Poo MM. Propagation
of activity-dependent synaptic depression in simple neural networks. Nature.
1997 Jul 31;388(6641):439-48.
Wilcox KS, Fitzsimonds RM, Johnson B,
Dichter MA. Glycine
regulation of synaptic NMDA receptors in hippocampal neurons. J Neurophysiol.
1996 Nov;76(5):3415-24.
Fitzsimonds RM, Dichter MA. Heterologous
modulation of inhibitory synaptic transmission by metabotropic glutamate receptors
in cultured hippocampal neurons.
J Neurophysiol. 1996 Feb;75(2):885-93.
reiko.fitzsimonds@yale.edu
website
http://neuron.med.yale.edu |
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