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Synaptic transmission,
neuronal plasticity and mechanism of memory. My
laboratory is interested in neurobiological mechanisms of learning and memory
-- from the molecular to the behavioral levels -- with a major focus is on rapid
forms of learning. The brain structures on which we have concentrated include
the hippocampus, amygdala, and perirhinal cortex. Collectively, they are implicated
in aspects of declarative and emotional learning as well as aging-related forms
of neuropathology and accompanying behavioral or mental changes. One
working hypothesis is that rapid learning emerges from use-dependent modification
in pre-existing synaptic connections. Accordingly, a long-term thrust of my research
has been to develop techniques that enable a rigorous analysis of the biophysics
and microphysiology of synapses in brain structures -- such as the hippoampus,
amygdala and perirhinal cortex -- that have been implicated in rapid learning.
To this end, we apply powerful optical and biophysical techniques to study rapid
and persistent synaptic modifications. The in vitro methods include patch-clamp
recording, -- quantal analysis, confocal microscopy and calcium imaging, and anatomical
reconstructions of recorded neurons. More recently
the research has expanded to include characterization of the neural circuits and
systems involved in rapid learning. Methods have included tracing axonal projections
of physiologically characterized neurons, in vivo behavioral neurophysiological
studies, and in vivo analysis of a rapidly-induced form of Pavlovian conditioning
whose underlying circuitry appears to be simple. The experimental knowledge we
gain about synapses, circuits and systems is being incorporated into computational
models for theoretical studies. 
Figure
caption: Whole-cell recordings of
hippocampal mossy-fiber synaptic currents showing paired-pulse facilitation before
and after the induction of long-term synaptic potentiation (LTP). Top traces
are individual currrents: lower traces are averages. Several lines of evidence
suggested a presynaptic mechanism for LTP expression in these synapses (from Xiang
et al. 1994). Recent
publications: McGann
JP, Moyer JR Jr, Brown TH. Predominance
of late-spiking neurons in layer VI of rat perirhinal cortex. J Neurosci.
2001 Jul 15;21(14):4969-76.
Lee HJ, Choi JS, Brown TH, Kim JJ. Amygdalar
nmda receptors are critical for the expression of multiple conditioned fear responses.
J Neurosci. 2001 Jun 1;21(11):4116-24.
Beggs JM, Moyer JR Jr, McGann
JP, Brown TH. Prolonged
synaptic integration in perirhinal cortical neurons. J Neurophysiol. 2000
Jun;83(6):3294-8. thomas.brown@yale.edu
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