[Neuroscience] Coactivation of pre- and postsynaptic signaling mechanisms determines cell-specific spike-timing-dependent plasticity

John H. via neur-sci%40net.bio.net (by bingblat from goaway.com.au)
Mon Apr 23 04:34:03 EST 2007

23/04/2007 7:22PM

1: Neuron. (2007 Apr 19;54(2):291-301

Coactivation of pre- and postsynaptic signaling mechanisms determines
cell-specific spike-timing-dependent plasticity.

Synapses may undergo long-term increases or decreases in synaptic strength
dependent on critical differences in the timing between pre-and postsynaptic
activity. Such spike-timing-dependent plasticity (STDP) follows rules that
govern how patterns of neural activity induce changes in synaptic strength.
Synaptic plasticity in the dorsal cochlear nucleus (DCN) follows Hebbian and
anti-Hebbian patterns in a cell-specific manner. Here we show that these
opposing responses to synaptic activity result from differential expression
of two signaling pathways. Ca(2+)/calmodulin-dependent protein kinase II
(CaMKII) signaling underlies Hebbian postsynaptic LTP in principal cells. By
contrast, in interneurons, a temporally precise anti-Hebbian synaptic
spike-timing rule results from the combined effects of postsynaptic
CaMKII-dependent LTP and endocannabinoid-dependent presynaptic LTD. Cell
specificity in the circuit arises from selective targeting of presynaptic
CB1 receptors in different axonal terminals. Hence, pre- and postsynaptic
sites of expression determine both the sign and timing requirements of
long-term plasticity in interneurons.

PMID: 17442249 [PubMed - in process]

Cell Biology & Anatomy Professor's Results on Neural Plasticity


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Prof Thanon Tzounopoulos has uncovered novel forms of synaptic plasticity
that occur at the very first step in the processing of "sound" in the
central nervous system. These findings may be relevant for understanding the
mechanisms of human Tinnitus.

Newswise - The Chicago Medical School (CMS) of the Rosalind Franklin
University of Medicine and Science (RFUMS) today announced that Assistant
Professor of Cell Biology & Anatomy, Athanasios Tzounopoulos, has uncovered
novel forms of synaptic plasticity that occur at the very first step in the
processing of sound in the central nervous system. His findings are being
released today in Neuron, one of two leading journals in Neuroscience.

"The ability to observe synaptic plasticity and uncover its cellular
mechanisms at such an early, relatively unprocessed stage allows us to study
the role of these mechanisms in sensory processing," said Professor
Tzounopoulos. "Our findings also show that the brain is able to change
itself as a result of previous experience at places where processing is much
simpler and better understood. This new capability could have a significant
impact on our understanding and cures for disorders caused by neural
plasticity-like mechanisms," he added.

These findings may be relevant for understanding the mechanisms of human
tinnitus. Tinnitus is the perception of ringing, buzzing, roaring, or other
noises in the ears or head - when there is no external source of the noise.
It is estimated that more than 50 million Americans experience tinnitus to
some degree. Of these, about 12 million have tinnitus severe enough to seek
medical attention. Many learn to ignore the sounds and experience no major
effects. However, about two million patients are so seriously debilitated
that they cannot function normally, finding it difficult to hear, work or
sleep. Though research is providing more evidence for the causes and
treatments of tinnitus, there is no real understanding of the biological
bases of tinnitus, nor are there any treatments that help most sufferers.
Recent studies point to the central nervous system as the site for the
maintenance of tinnitus. Moreover, animal models of tinnitus indicate a role
for the dorsal cochlear nucleus (DCN, an auditory brainstem nucleus), the
brain area where Professor Tzounopoulos performed his studies.

"It is quite possible that transient exposure to intense sound might induce
long-term changes in the balance of excitation and inhibition in the DCN,
through the mechanisms described in our recent findings. Our studies, by
providing a detailed understanding on how this plasticity is induced,
expressed, and modulated at the cellular level may ultimately lead to
treatments for tinnitus" said Professor Tzounopoulos.

According to these recent findings, newly formed hypotheses suggest that
concerted operation of different forms of synaptic plasticity gate sensory
activation of the DCN and can lead to activity-dependent modulation of
timing precision. Timing is an important feature in the brain and especially
in the auditory system. Many neurons in the auditory system are known for
their ability to fire action potentials that occur in a precise temporal
relationship to the stimulus (phase locking). Activity-dependent modulation
of spike timing precision through these mechanisms is a new concept that may
allow sensory systems to adapt to different patterns of sensory activity and
to properly integrate and encode varying sensory stimuli.

Recent studies have shown that more robust and faithful brainstem timing
encoding is observed in trained individuals (musicians) compared to
untrained individuals (non-musicians). While these types of learning
phenomena have been attributed to cortical plasticity until now, our studies
suggest that the brainstem itself has the mechanisms and the capability to
support such learning. Similar studies have established that brainstem
timing precision serves as a reliable marker of individuals with learning
disabilities. Faulty mechanisms of neural timing at the brainstem may be the
biological basis of malfunction in children with learning disabilities.
"Therefore, elucidation of mechanisms underlying synaptic plasticity and
timing precision in the brainstem may provide the cellular basis for these
learning disabilities," said Professor Tzounopoulos.

Rosalind Franklin University of Medicine and Science educates medical
doctors, health professionals, and biomedical scientists in a personalized
atmosphere. The University is located at 3333 Green Bay Road, North Chicago,
IL 60064, and encompasses Chicago Medical School, College of Health
Professions, Dr. William M. Scholl College of Podiatric Medicine, and School
of Graduate and Postdoctoral Studies. Visit us at
http://www.rosalindfranklin.edu and http://www.lifeindiscovery.com.

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