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By Eamon Quick

By Eamon Quick. The Rundown. Long-Term Potentiation (LTP) : activity-dependent increase in synaptic activity Dependent upon NMDA receptor activation Favors back-propagating action potentials (b-APs) and higher postsynaptic concentrations of Ca 2+

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By Eamon Quick

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  1. By Eamon Quick

  2. The Rundown • Long-Term Potentiation (LTP): activity-dependent increase in synaptic activity • Dependent upon NMDA receptor activation • Favors back-propagating action potentials (b-APs) and higher postsynaptic concentrations of Ca2+ • A-type K+ channels: high-density towards distal dendrites • Reduce amplitude of b-APs • Reduce excitatory postsynaptic potentials (EPSPs) • Raise threshold for local AP initiation • Altering these channels changes their local excitability • Characteristic: fast, short-term outward current flow (IA), which can be reduced by a: • Hyperpolarized shift in inactivation curve • Depolarized shift in activation curve

  3. Point of This Study • 1) To determine if the IA can be associated with the LTP phenomenon • 2) If so, if it can be detected locally in the dendrites

  4. Methods Tissue: • CA1 hippocampal pyramidal neurons from rats Methods: • Whole-cell recordings • For detecting action potentials at the dendrites and soma • Calcium ion imaging (via Ca2+ indicator bis-fura-2) • For detecting intracellular calcium concentrations • Patch-clamp recordings • For measuring current flow from dendrites

  5. Data!

  6. Fig.1 LTP! Using the TBP protocol, the authors showed that they could induce LTP in the distal dendrites with paired stimulations

  7. Fig.1 NMDA-Rs necessary! NMDA antagonists were used to verify that NMDA receptors were involved in the induction of the observed LTP

  8. Fig.2 Less excitation! For normal b-AP, after 50um, calcium concentration drops significantly… b-AP injected into soma!

  9. Fig.2 …in both measurements of calcium ion signal and action potential amplitude!

  10. Fig.3 When inducing LTP, distal dendrites show increased calcium signal, but not proximal dendritic areas! Since the stimulated areas are distal, this shows local effects of LTP.

  11. Fig.3 Local excitability! Local effect of LTP-induced increase in calcium concentration

  12. Fig.4 Expected LTP, with data suggesting that sodium current not involved in the b-AP. NMDA still necessary… …and local stimulation important as well

  13. Fig.4 Various graphs showing how LTP could be blocked with NMDA-R antagonists and how it was not seen distal from the area of local synaptic stimulation. Shows local excitability.

  14. Fig.5 Antidromic stimulation simulating real b-AP. From axon, not soma!

  15. Fig.5 Summation of the increase of intracellular calcium near the area of stimulation Increase of synaptic strength

  16. Fig.6 Same as prior figure, but this time with NMDA-R antagonists!

  17. Fig.7 Dendritic patch-clamp recordings of current flow, and the increased synaptic output during LTP

  18. Fig.8 Less outward current! IA current decrease due to LTP, seen at different voltage protocols

  19. Fig.8 More channels inactivated! IA changes with LTP! IA current decrease due to LTP

  20. Results • 1) IA reduction is associated with LTP • 2) This change occurs locally • The evidence: • Enhancement of calcium signal from b-APs where synapses are potentiated • Amplification of b-APs at these areas • Decreased b-AP enhancement and calcium signal farther away from input area • Steady-state inactivation range of A-type K+ channels shifted towards hyperpolarized potentials • Dependence on LTP • IA modulation is a form of intrinsic plasticity

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