Research descriptions:
I found the previous studies from Dr.
Disterhoft’s laboratory describing aging- and
learning-related changes in the excitability of hippocampal pyramidal
neurons and their
implications in aging-related learning deficit to be very fascinating,
and joined his team in
1999 to examine the ionic mechanisms that contribute to these changes.
We focused on
characterizing the currents underlying the slow afterhyperpolarization
(slow AHP) in CA1
pyramidal neurons, as these play an important role in regulating spike
frequency
accommodation and are modulated by many neurotransmitters, neuromodulators,
and
neuropeptides that have been implicated in aging and in learning.
We have determined that
changes in the slow Ca2+-activated K+ current (the sIAHP) partially
mediate the aging- and
learning-related excitability changes in CA1 pyramidal neurons. For
aging tissues, the
enhancement in the sIAHP cannot be totally attributed to the increase
in the L-type Ca2+
current previously reported by us and other laboratories. Ongoing
projects here include further
delineating the cellular mechanisms that lead to a persistent increase
in the sIAHP in aging, and a transient (up to 7 days after acquisition
of a behavioral paradigm) decrease in the sIAHP in learning.
Activation of the slow AHP is Ca2+-dependent, and has been linked
to Ca2+ influx
from different Ca2+ channels, Ca2+ permeant receptors, and release
from intracellular stores.
Given the non-uniform distribution of different types of Ca2+ channels
and Ca2+ permeant
receptors across the somato-dendritic axis, I next examined the slow
AHP activated by
different patterns of synaptic stimuli. Our most recent study shows
that during periods of
high frequency, intense synaptic events, the slow AHP profoundly limits
the magnitude of
the NMDA receptor-dependent afterdepolarization, thereby affecting
information
throughput in CA1 pyramidal neurons.
My long term research goal is to understand
how neurons and neural circuits underlie behavior. However, my studies
in Dr. Disterhoft’s laboratory have helped me
realize that an important step toward this goal is to understand how
neurons process
information. As an extension to the “cholinergic and Ca2+ hypotheses
in aging”, I am
currently characterizing the M-current (which contributes to the medium
AHP at
depolarized membrane potentials) in young and aging CA1 pyramidal
neurons using a panel
of electrophysiological and immnuohistochemical techniques. .
For my curriculum vitae please click
here
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Last updated: Sunday, July 21, 2002
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