PhD proposal (December 2010)

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PhD proposal (December 2010)

  1. 1. PhD proposal Synaptic integration of input in a realistic in vivo environment Miha Pelko Advisors:Mark van Rossum Clemens Boucsein
  2. 2. Realistic synaptic integration Given same inputs to the neuron, the output response might vary due to: • Channel noise (stochastic channel opening) • Synaptic background activity • Variability of released neurotransmitter • Other noise (thermodynamic) Difficult to measure in vivo.Faisal et al., 2008, Nature Rev. Neuroscience
  3. 3. In-vitro studies Input integration in single neuronsA new cellular mechanism for coupling Dendritic discrimination of temporal inputinputs arriving at different cortical layers sequences in cortical neuronsLarkum, Zhu, Sakmann (1999), Nature Branco, Clark, Hausser (2010), Science Spike timing dependent plasticity (STDP)Regulation of synaptic efficacy by Synaptic modifications in cultured hippocampalcoincidence of postsynaptic APs and neurons: dependence on spike timing, synapticEPSPs. strength, and postsynaptic cell type.Markram et al. (1997), Science Bi, Poo (1998), J Neurosci.
  4. 4. In-vitro studies Input integration in single neuronsA new cellular mechanism for coupling Dendritic discrimination of temporal inputinputs arriving at different cortical layers sequences in cortical neuronsLarkum, Zhu, Sakmann (1999), Nature Branco, Clark, Hausser (2010), Science Spike timing dependent plasticity (STDP)Regulation of synaptic efficacy by Synaptic modifications in cultured hippocampalcoincidence of postsynaptic APs and neurons: dependence on spike timing, synapticEPSPs. strength, and postsynaptic cell type.Markram et al. (1997), Science Bi, Poo (1998), J Neurosci.
  5. 5. How much can we really learn from quiescent in-vitro experiments Typical in-vitro setting
  6. 6. How much can we really learn from quiescent in-vitro experiments More realistic in-vivo environment
  7. 7. Effects of background activity1. No background activity ? Hô, Destexhe, 2000, J Neurophysiol
  8. 8. Effects of background activity1. No background activity ?2. Background activity ? Hô, Destexhe, 2000, J Neurophysiol
  9. 9. Background activity enhances synaptic responsiveness1. 1. ? 2.2. ? Hô, Destexhe, 2000, J Neurophysiol
  10. 10. General research questionsWhat is a realistic synaptic integration in single neuron? – Non-linear effects in input integration – Output dependence on input correlation – Output dependence on the input location (proximal/distal)Relates to: – Rate Vs. Temporal coding – Limitations of integrate and fire models?
  11. 11. PhD project Non-linearity effectsInput spike trains EPSP
  12. 12. Non-linearity effectsInput spike trains EPSP
  13. 13. Non-linearity effectsInput spike trains EPSP
  14. 14. Non-linearity effectsInput spike trains ? EPSP
  15. 15. Non-linearity effectsInput spike trains Voltage trace
  16. 16. SimulationsImplementing a compartmental neuronal model (using Neuron simulator) with realistic – morphologies – channel dynamics – channel distributionsCreating a set of input protocols for evaluating – non-linear integration effects – input correlation effects – input location effects
  17. 17. SimulationsImplementing a compartmental neuronal model (using Neuron simulator) with realistic – morphologies – channel dynamics – channel distributionsCreating a set of input protocols for evaluating – non-linear integration effects – input correlation effects – input location effects
  18. 18. Experimental - Dynamic photo stimulationBoucsein et al., 2005, Nawrot et al., 2009,J neurophysiol Front Neural Circuits

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