Prsentation PowerPoint

1
Dynamics of excitatory synaptic components in
sustained firing at low rates
C. Wyart, J.-F. Léger, C. Herr, S. Cocco, D.
Chatenay, L. Bourdieu Laboratoire de Dynamique
des Fluides Complexes UMR 7506, ULP,
Strasbourg Laboratoire de Neurobiologie
Cellulaire et Moléculaire UMR 8544, ENS, Paris
2
Low frequency f persistent activity of neuronal
networks working memory in the prefrontal cortex
1) Standard model the role of propagation of
reverberating excitation ?
High efficiency of recurrent synapses
2) Role of the temporal synaptic dynamics (Wang,
1999) ?
SLOW positive feedback mechanisms tpos To allow
refiring after a long delay
Fast negative feedback mechanisms tneg to
prevent high frequency firing

• synchronous networks tpos gt1/f
• asynchronous networks tpos gt tneg

R-NMDA
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The case of highly synchronous glutamatergic
netwoks
AUTAPSES

• model of synchronous networks
• silences and self maintained active states
• no propagation through the network
• low and very low frequency regimes

Cell attached recordings
4
Neuronal networks of controlled architecture
towards neuron-electronic interface

• Spatial adhesion contrats

Fluorosilane vs. Polylysine

• The physiological activity is preserved.

Électrophysiology Type of
neurons Synapses
50µm
50µm
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• Orientation of the connectivity

•  known  architecture

• interfacing with MEA

1ers voisins
90
2nds voisins
40
Direct connexion

• fixed position of neurons
• nature of neurons
• connexion efficiency

Optimization of neuron to electronic interface
Connexion efficiency
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Persistence at low frequency (10Hz)
II weeks
MK801, APV

• Remove - the slow component of the EPSP
• - the persistent activity

- Timescale of the EPSPs slowest component gt
1/frequency - Persistence at 10 Hz requires
R-NMDA
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Persistence at very low frequency (2Hz)
III-IV weeks
Irregular very low frequency firing
MK801, APV

• - slightly modifies the slow component
• - Do not prevent the persistence of activity

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Persistence at very low frequency (2Hz)
III-IV weeks
Asynchronous miniatures
Very slow synaptic component

• removes
• the slow component
• asynchronous miniatures
• persistence of activity at very low frequency

EGTA-AM
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Persistence at very low frequency (2Hz)
glutamate
mgluR group I
Ca2
out
Ca2
Intracellular Calcium stores
in
Slow depolarizing conductance (ICAN cationic non
selective calcium activated conductance ?)
L-type Ca channels
Congar, Ben-ari 1997
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Role of the late release of glutamate

• Experiments with EGTA
• Irregular bursts with APV/MK801
• Experiments with strontium

Strontium diminish the fast release, increase
the late release
Strontium Increases persistence
Strontium 3mM
Ca 3mM
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Persistence at very low frequency (2Hz)
EGTA-AM, MCPG, Nifedipin

• Persistence at very low frequency
• intracellular calcium dependant conductance
• presumably ICAN
• role of asynchronous release
• Timescale of the slowest depolarizing component
  of the EPSP gt1/frequency

12

• Model rate control
• Fast negative feedback mechanism
• Drop of the cell resistance
• Slow positive feedback
• The slowest depolarizing component of the EPSP

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• What about hetero-synapses ?

paires isolées
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• Conclusion
• Direct demonstration of the role of the temporal
  synaptic dynamics in the persistence of activity
  at low firing rate
• Identification of two conductances NMDA et ICAN
• - in vivo evidences of R-NMDA implications in
  persistence of activity
• - NMDAR antagonists in the prefrontal cortex
  impair working memory in rat performing a spatial
  delayed alternation task (Verma 1996 and
  Romanides 1999)
• NMDA antagonists abolish epileptiform discharges
  induced by picrotoxin in hippocampal slices (Lee,
  Hablitz, 1990, 1991)
• induction by NMDA of "theta-like" rhythmic
  oscillations and bursts in hippocampal slices
  (Bonansco et al., 2002)
• - in vivo role of mGluRs in persistence of
  activity
• Evidence for a role of a mGluRs synaptic
  activation during prolonged epileptiform
  discharges induced by bicuculline and 4-AP (Lee
  et al., 2002)
• when glutamate ionotropic receptors were
  blocked, a long lasting post synaptic component
  sensitive to MCPG allowed the signal propagation
  elicited by stimulation of association fibers in
  the hippocampus (Sugitani et al., 2002).