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The role of inhibition in
synaptic plasticity
Synaptic plasticity is customarily associated with
excitatory neurotransmission in both hebbian and homeostatic mechanisms. The
same is true for the plasticity associated with the repositioning of sensory
maps in primary sensory cortex. However, there has always been compelling
evidence to suggest that inhibitory neurons contribute to
experience-dependent plasticity in sensory cortex. For example, inhibitory
neurons are both numerous and diverse in sensory cortical areas. They shape
sensory evoked receptive field properties of cortical neurons and are
sensitive to changes in activity. In addition, the functional complexity of
GABAA receptor mediated inhibitory neurotransmission is equally
diverse. It is often assumed, that through this diversity, exists a
specialization of inhibitory function. Based on this framework, my lab is
focused on four questions toward understanding the role of inhibition in
synaptic plasticity:
1) What types of inhibitory neurons
contribute to sensory map plasticity?
2) What is the mechanism by which this
plasticity is mediated? For example, what is the biophysical consequence of
sensory deprivation and does this implicate homeostatic or hebbian forms of
plasticity?
3) Do deprivation induced biophysical
changes in inhibitory neurons affect sensory processing?
4)
How can we use sensory systems to understand plastic changes that occur in
mechanisms of disease, such as epilepsy?
The overall goal of my
research is to establish functional roles for specialized inhibitory
circuits in synaptic plasticity and sensory processing. In order to
accomplish these goals, I use a combined molecular and physiological
approach to understand biophysical consequences of sensory deprivation. I
employ the whole cell voltage clamp technique to measure GABAA
receptor mediated currents in physiologically identified neurons in layer 4
of the primary somatosensory cortex of mice. These studies will reveal new,
fundamental roles of intracortical inhibition in synaptic plasticity by
cell-type-specific inhibitory circuits and implicate inhibition in non-hebbian
mechanisms of plasticity in the re-organization of sensory maps.
Functional
properties of sensory deprived neurons.
A, Schematic of pattern of main facial whiskers in rows (A,B,C,D,E). B,
Sensory deprivation is achieved through selective whisker removal. This is a
schematic of our whisker removal pattern. C, slice in recording
chamber showing the pattern of barrels that correspond to each facial
whisker in A, B. Each whisker on the contralateral face corresponds
to a barrel in layer 4. D, Cytochrome oxidase stained section in
whisker trimmed animal shown in B. The lighter staining corresponds
to decreased activity in barrels that are postsynaptic to sensory pathways
aligned with missing whiskers.
Selected Publications:
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Krook-Magnuson EI, Li P, Paluszkiewicz SM, Huntsman MM. Tonically active inhibition selectively controls feedforward circuits in mouse barrel cortex. J Neurophysiol. PMID: 18509076
May 2008 -
Krook-Magnuson EI and Huntsman MM.
The transience of interneuron diversity just sped up. PNAS
104, 16723-16724, 2007 -
Krook-Magnuson EI and Huntsman MM. Excitability of cortical
neurons depends upon a powerful tonic conductance in inhibitory
networks, Thalamus & Related Systems 3:115-120, 2007
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Huntsman MM, Huguenard JR. Fast IPSCs in the thalamic reticular nucleus
require the GABA_A Beta 1 subunit. J Physiol . 572:
459-475, 2006
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Porcello DM, Huntsman MM, Mihalek RM, Homanics GE, Huguenard JR.
Intact Synaptic GABAergic Inhibition and Altered Neurosteroid
Modulation of Thalamic Relay Neurons in Mice Lacking delta Subunit.
J Neurophysiol. 89:1378-86, 2003-
Sohal VS, Huntsman MM, Huguenard JR. Reciprocal inhibitory connections regulate
the spatiotemporal properties of intrathalamic oscillations. J Neurosci.
20:1735-1745, 2000
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Huntsman MM, Huguenard JR. Nucleus-specific differences in GABAA receptor-mediated
inhibition are enhanced during thalamic development. J. Neurophysiol.
83:350-358,
2000
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Huntsman MM, Porcello DM, Homanics GE, DeLorey TM, Huguenard JR. Reciprocal
inhibitory connections and network synchrony in the mammalian thalamus.
Science 283:541-543, 1999
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Huntsman MM, Munoz A, Jones EG. Temporal modulation of GABAA receptor subunit
gene expression in developing monkey cerebral cortex. Neuroscience
. 91:1223-45,
1999
Munoz A, Huntsman MM, Jones EG. GABA(B) receptor gene
expression in monkey thalamus.
J Comp Neurol.
390:278-96, 1998-
Jones EG, Tighilet B, Tran BV, Huntsman MM. Nucleus- and cell-specific
expression of NMDA and non-NMDA receptor subunits in monkey thalamus.
J Comp Neurol. 3:397:371-93, 1998
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Huntsman MM, Tran BV, Potkin SG, Bunney WE Jr, Jones EG. Altered ratios
of alternatively spliced g2S and g2L GABAA receptor subunit mRNAs in prefrontal
cortex of schizophrenics. Proc. Natl. Acad. Sciences. 95:15066-15071,
1998
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Huntsman MM, Jones EG. Expression of a3, b3 and g1 GABAA receptor subunit
mRNAs in the visual cortex and lateral geniculate nucleus of monkeys.
Neuroscience. 87:385-400,
1998
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Huntsman MM, Leggio MG, Jones EG. Nucleus-specific expression of ten GABAA
receptor subunit mRNAs in monkey thalamus. J. Neurosci.
16:3571-3589
,
1996
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Huntsman MM, Woods TM, Jones EG. Laminar patterns of expression of GABA-A
receptor subunit mRNAs in monkey sensory motor cortex.
J Comp Neurol.
362:565-82, 1995 -
Akbarian S, Huntsman MM, Kim JJ, Tafazzoli A, Potkin SG, Bunney WE Jr,
Jones EG. GABAA receptor subunit gene expression in human
prefrontal cortex: comparison of schizophrenics and controls.
Cereb Cortex.
5:550-60, 1995-
Huntsman MM, Leggio MG, Jones EG. Expression patterns and deprivation
effects on GABAA receptor subunit and GAD mRNAs in monkey lateral
geniculate nucleus.
J Comp Neurol.
352:235-47, 1995
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Hendry SH, Huntsman MM, Vinuela A, Mohler H, de Blas AL, Jones EG.
GABAA receptor
subunit immunoreactivity in primate visual cortex: distribution in
macaques and humans and regulation by visual input in adulthood.
J Neurosci.
14:2383-40, 1994
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Huntsman MM, Isackson PJ, Jones EG. Lamina-specific expression and
activity-dependent regulation of seven GABAA receptor subunit mRNAs in
monkey visual cortex.
J Neurosci.
14:2236-59, 1994
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Benson DL, Huntsman MM, Jones EG. Activity-dependent changes in GAD and
preprotachykinin mRNAs in visual cortex of adult monkeys.
Cereb Cortex.
4:40-51, 1994
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Isackson PJ, Towner MD, Huntsman MM. Comparison of mammalian, chicken and
Xenopus brain-derived neurotrophic factor coding sequences.
FEBS Lett. 285:260-4, 1991
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Isackson PJ, Huntsman MM, Murray KD, Gall CM. BDNF mRNA expression is
increased in adult rat forebrain after limbic seizures: temporal
patterns of induction distinct from NGF. Neuron.
6:937-48, 1991
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