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