Synaptic Plasticity and optimization by Astrocytes

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Synaptic Plasticity and optimization by Astrocytes
P. Jung Dept. of Physics and Astronomy and
Quantitative Biology Institute, Ohio University
S. Nadkarni Center for Theoretical Biological
Physics, UCSD
Financial support NSF
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Astrocytes and Neurons
Nedergaard et al., TINS 26, 523 (2003)
astrocytes do not fire action potentials one
astrocyte contacts 1000s of synapses!
Gap junctions
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Astrocyte-Neuron arrangement
R. Douglas Field, Sci. Am., April 2004
listen to neurons (all major receptors
present) release neurotransmitter (Glu, ATP,
) modulate neuronal excitability and synaptic
transmission (Kang et al., Nat.Neurosci 1,
1998, Fiacco et al. J. Neurosci 2004)
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The Tripartite Synapse
(Araque et al., TINS 22 (1999))
Fellin et al., Physiology 21, 208 (2006)
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Modulation and optimization of synapse

• Activity dependent increase in presynaptic Ca2
  and synaptic transmission probability(Kang et
  al. 1998, Fiacco et al.2004)

• Neurotransmitter resource limited --gt depletion
  of vesicles, refractory times, postsynaptic
  depression

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Presynaptic vesicle release
S. Nadkarni P.J., Phys. Biol. 4, 2007
Evoked vesicle release probability P
0.2 Ca2cpre300µM
Spontaneous release rate (matched to data)
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How much glutamate is released?
Tsodyks M, and Markram H (1997) Proc Natl Acad
Sci USA. 94 719
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Synaptic activation of astrocytes
S. Nadkarni P.J., Phys. Biol. 1, 2004
Production of IP3 (p)
Ca2 dynamics in astrocyte
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Glutamate stimulation of cultured astrocytes
Cornell-Bell et al. Science, 247, 373 (1990)
S. Nadkarni and P.J. Phys. Biol. 1 (2004)
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Astrocytes release neurotransmitter
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Synaptic transmission
Kang et al., Nat. Neurosc. 1998
2 active zones, P 0.2
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Other Synaptic Designs
N 2, P variable
The lower the baseline fidelity P the larger the
maximum potentiation by astrocyte
The lower the baseline fidelity P the larger the
range of plasticity
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Other Synaptic Designs
P0.2, N variable
The more active zones the larger the maximum
potentiation and plasticity
BUT Metabolic cost largeSpace limited
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Summary
Astrocytes enhance synaptic transmission We
predict optimal synaptic transmission
Experimental enhancement by astrocyte close to
predicted optimum
Collaborators
Herbert Levine, CTBP/UCSD
Thanks
Eshel Ben-Jacob (Tel Aviv) Vladislav Volman,
CTBP/UCSD
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Publications
S. Nadkarni and P.J., Dressed Neuronmodeling
neural-glial interactions,Phys. Biol. 1, 35
(2004) S. Nadkarni and P.J., Synaptic inhibition
and pathological hyperexcitability through
enhanced neuron-astrocyte interaction, J.Integr.
Neurosci, 4, 1 (2005) S.Nadkarni and P.J.,
Modeling synaptic transmission of the tripartite
synapse, Phys. Biol. 4, 1 (2007) S. Nadkarni,
P.J. and H. Levine, Astrocytes optimize synaptic
transmission of information, submitted
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Astrocytes - now
No action potentials, but Ca2-excitable!
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Astrocytes - then
The prejudice that the relation between
neuroglial fibers and neuronal cells is similar
to the relation between connective tissue and
muscle or gland cells, that is, a passive weft
for merely filling and support (and in the
best case, a gangue for taking nutritive juices),
constitutes the main obstacle that the researcher
needs to remove to get a rational concept about
the activity of the neuroglia. S Ramon y Cajal
Nobel Price in Medicine 1906Discoverer of the
neuron
(Blocks of brain soaked in silver nitrate)
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Design Parameters for Synapses
P Probability for a postsynaptic current
during a 2ms action potential
N Number of active zones i.e. machineries
from which vesicles are released.
Hippocampal neurons N 1,2, P 0.2
(average) Calix of Held (auditory system N
600, P 0.99
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The role of astrocytes in Epilepsy
in astrocytes from epileptic foci mGluRs are
overexpressed by a factor of about 20 (rat
models and human) (Ulas et al., Glia 30, 352
(2000), Tang and Lee, J. Neurocytology, 30, 137
(2001), Aronica et al. Europ.J. Neurosci.,
12, 2333 (2000), Enhanced IP3 Hydrolysis and
increased Ca2 spikes during epileptic seizure
(Ong et al. J. Neurochem. 72, 1574 (1999) More
spontaneous astrocytic calcium spikes in
epileptic (Tashiro et al., J. Neurobiol. 50,
45 (2002)
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Bifurcation Diagram
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Higher abundance of mGluRs
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Higher abundance of mGluRs
Inject dc current
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Pyramidal Neuron Astrocyte
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Model for Pyramidal Cell
Slow inward currentfrom astrocyte
Pinsky and Rinzel J. Comp. Neurosc. 1, 39 (1994)
soma
dendrites
8-variable conductance-based model
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Astrocyte talks to pyramidal neuron
Parpura and Haydon, PNAS, 97, 8629 (2000)
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How much glutamate is there?
Volume of cleft
concentration in cleft
only few Glu molecules bind to receptors
Glu removed rapidly through Glu transporters (W.
Holmes, Biophys. J. 1995)