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Synaptic integration of input in a realistic in vivo environment
Miha Pelko
Advisors:
Mark van Rossum Clemens Boucsein
PhD proposal
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
Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs.
Markram et al. (1997), Science
In-vitro studies
Dendritic discrimination of temporal input sequences in cortical neurons
Branco, Clark, Hausser (2010), Science
A new cellular mechanism for coupling inputs arriving at different cortical layers
Larkum, Zhu, Sakmann (1999), Nature
Input integration in single neurons
Spike timing dependent plasticity (STDP)
Synaptic modifications in cultured hippocampalneurons: dependence on spike timing, synaptic strength, and postsynaptic cell type.
Bi, Poo (1998), J Neurosci.
Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs.
Markram et al. (1997), Science
In-vitro studies
Dendritic discrimination of temporal input sequences in cortical neurons
Branco, Clark, Hausser (2010), Science
A new cellular mechanism for coupling inputs arriving at different cortical layers
Larkum, Zhu, Sakmann (1999), Nature
Input integration in single neurons
Spike timing dependent plasticity (STDP)
Synaptic modifications in cultured hippocampalneurons: dependence on spike timing, synaptic strength, and postsynaptic cell type.
Bi, Poo (1998), J Neurosci.
How much can we really learn from quiescent in-vitro experiments
Typical in-vitro setting
How much can we really learn from quiescent in-vitro experiments
More realistic in-vivo environment
Effects of background activity
?1. No background activity
Hô, Destexhe, 2000, J Neurophysiol
Hô, Destexhe, 2000, J Neurophysiol
?
?
1. No background activity
2. Background activity
Effects of background activity
Background activity enhances synaptic responsiveness
Hô, Destexhe, 2000, J Neurophysiol
2.
?
?
1. 1.
2.
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?
Non-linearity effects
EPSP
Input spike trains
PhD project
Non-linearity effects
EPSP
Input spike trains
Non-linearity effects
EPSP
Input spike trains
Non-linearity effects
?EPSP
Input spike trains
Voltage traceInput spike trains
Non-linearity effects
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
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
Experimental - Dynamic photo stimulation
Boucsein et al., 2005, J neurophysiol
Nawrot et al., 2009, Front Neural Circuits
