1. PhD proposal
Synaptic integration of input in a realistic in
vivo environment
Miha Pelko
Advisors:
Mark van Rossum Clemens Boucsein

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. In-vitro studies
Input integration in single neurons
A new cellular mechanism for coupling Dendritic discrimination of temporal input
inputs arriving at different cortical layers sequences in cortical neurons
Larkum, Zhu, Sakmann (1999), Nature Branco, Clark, Hausser (2010), Science
Spike timing dependent plasticity (STDP)
Regulation of synaptic efficacy by Synaptic modifications in cultured hippocampal
coincidence of postsynaptic APs and neurons: dependence on spike timing, synaptic
EPSPs. strength, and postsynaptic cell type.
Markram et al. (1997), Science Bi, Poo (1998), J Neurosci.

4. In-vitro studies
Input integration in single neurons
A new cellular mechanism for coupling Dendritic discrimination of temporal input
inputs arriving at different cortical layers sequences in cortical neurons
Larkum, Zhu, Sakmann (1999), Nature Branco, Clark, Hausser (2010), Science
Spike timing dependent plasticity (STDP)
Regulation of synaptic efficacy by Synaptic modifications in cultured hippocampal
coincidence of postsynaptic APs and neurons: dependence on spike timing, synaptic
EPSPs. strength, and postsynaptic cell type.
Markram et al. (1997), Science Bi, Poo (1998), J Neurosci.

5. How much can we really learn from quiescent
in-vitro experiments
Typical in-vitro setting

6. How much can we really learn from quiescent
in-vitro experiments
More realistic in-vivo environment

7. Effects of background activity
1. No background activity
?
Hô, Destexhe, 2000, J Neurophysiol

8. Effects of background activity
1. No background activity
?
2. Background activity
?
Hô, Destexhe, 2000, J Neurophysiol

9. Background activity enhances synaptic
responsiveness
1. 1.
?
2.
2.
?
Hô, Destexhe, 2000, J Neurophysiol

10. General research questions
What 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. PhD project
Non-linearity effects
Input spike trains
EPSP

12. Non-linearity effects
Input spike trains
EPSP

13. Non-linearity effects
Input spike trains
EPSP

14. Non-linearity effects
Input spike trains
?
EPSP

15. Non-linearity effects
Input spike trains
Voltage trace

16. Simulations
Implementing a compartmental neuronal model (using
Neuron simulator) with realistic
– morphologies
– channel dynamics
– channel distributions
Creating a set of input protocols for evaluating
– non-linear integration effects
– input correlation effects
– input location effects

17. Simulations
Implementing a compartmental neuronal model (using
Neuron simulator) with realistic
– morphologies
– channel dynamics
– channel distributions
Creating a set of input protocols for evaluating
– non-linear integration effects
– input correlation effects
– input location effects

18. Experimental - Dynamic photo stimulation
Boucsein et al., 2005, Nawrot et al., 2009,
J neurophysiol Front Neural Circuits