Download The Liu lab is interested in synaptic transmission in the central

The Liu lab is interested in synaptic transmission in the central nervous system. In particular we
study how emotional stress and fear memories regulate excitatory and inhibitory synaptic
transmission in the cerebellum. This is a brain region that is important for learning/memory and
is involved in emotion. We use behavioral, electrophysiological, fluorescent imaging, and
cellular/molecular techniques. Our experiments are performed using brain slices and primary
neuronal cultures.
Emotional stress regulates glutamate receptor gene expression. Changes in emotional
state are known to alter neuronal excitability and can modify learning and memory formation. In
a recent study we have shown that a single exposure to a fear-inducing stimulus (Fig A) induces
a long-lasting increase in the transcription of the GluR2 subunit of the AMPA-type glutamate
receptor (Fig B) in cerebellar inhibitory interneurons (Liu et al, 2010). This reduces the AMPA
receptor Ca2+ permeability and alters synaptic efficacy (Fig C, IEM selective blocks GluR2lacking, Ca2+ permeable AMPA receptors).
We are currently investigating how a stress hormone, noradrenaline, promotes the
expression of the GluR2 gene in inhibitory interneurons and how enhanced GluR2 transcription
in inhibitory interneurons changes the activity of cerebellar circuits. We detect changes in GluR2
mRNA levels using real time single cell RT-PCR (Fig B), identify AMPA receptor subunit
composition at individual synapses using electrophysiological techniques (Fig C) and monitor
morphological changes using confocal microscopy.
Fear memories and synaptic plasticity. We are also interested in how fear memories
modulate GABA release from cerebellar inhibitory interneurons. We have found that an
excitatory transmitter, glutamate, enhances the release of GABA (Liu and Lachamp, 2006;
Lachamp et al, 2009). We are investigating (1) how a fear-stimulus alters synaptic
transmission, (2) what are the underlying molecular mechanism(s); (3) how synaptic plasticity
alters the activity of cerebellar neuronal circuits.
Recent Papers
Savtchouk, I. and Liu S. J. (2011) Remodeling of synaptic AMPA receptor subtype alters the
probability and pattern of action potential firing. J. Neurosci.31:501-511
Liu, Y, Formisano, L, Takayasu, Y, Savtchouk I, Szabó G, Zukin, R.S. and Liu S. J. (2010) A
single exposure to a fear-inducing stimulus induces GluR2 gene transcription and a
switch in synaptic AMPA receptor phenotype in cerebellar stellate cells. Nature
Neurosci. 13: 223-231.
Lachamp, P. M., Liu, Y and Liu, S. J. (2009) Glutamatergic modulation of cerebellar interneuron
activity is mediated by an enhancement of GABA release and requires PKA/RIM1signaling. J. Neurosci. 29:381-92.
Liu, S. J., Lachamp P, Liu Y, Savtchouk I and Sun L. (2008) Long-term synaptic plasticity in
cerebellar stellate cells. The Cerebellum. 7:559-62.
Sun, L. and Liu, S. J. (2007) Activation of extrasynaptic NMDA receptors induces a PKCdependent switch in AMPA receptor subtypes in mouse cerebellar stellate cells. J.
Physiol. 583:537-553.
Liu, S. J. (2007) Biphasic Modulation of GABA Release from stellate cells by glutamatergic
receptor subtypes. J. Neurophysiol. 98:550-556.
Liu S.J. and Zukin RS (2007) Ca2+-permeable AMPA receptors in synaptic plasticity and
neuronal death. Trends in Neurosci. 30:126-34.
Liu S. J. and Lachamp P (2006) The activation of excitatory glutamate receptors evokes a longlasting increase in the release of GABA from cerebellar stellate cells. J Neurosci.
26:9332-9
Liu S. J. and Cull-Candy S (2005) Subunit interaction with PICK and GRIP controls Ca2+permeability of AMPARs at cerebellar synapses. Nature Neurosci. 8:768-775.
Liu S. Q. and Kaczmarek LK. (2004) Aminoglycosides block the Kv3.1 potassium channel and
reduce the ability of inferior colliculus neurons to fire at high frequencies. J Neurobiol.
62:439-452
Liu, S. J. and S. G. Cull-Candy. (2002) Activity-dependent change in AMPA receptor properties
in cerebellar stellate cells. J. Neurosci. 22: 3881-9.
Liu, S. J. and S. G. Cull-Candy (2000) Synaptic activity at calcium-permeable AMPA receptors
induces a switch in receptor subtype. Nature 405: 454-458.