The HR-CORTEX project
"High-Resolution intracellular methods for conductance injection and measurement in cerebral cortical neurons"In collaboration with Romain Brette and Olivier Faugeras (Ecole Normale Supérieure, Paris), and with Thierry Bal and Yves Frégnac (UNIC, CNRS, Gif sur Yvette), we have obtained a three-year grant from the ANR. This project (coordinated by A. Destexhe) spanned 3.5 years from December 2006 to May 2010. The home pages of the project are at UNIC: http://cns.iaf.cnrs-gi f.fr/hr-cortex.html, and at the Ecole Normale Supérieure: http://www.di.ens.fr/~brette/HRCORTEX/index.html.
Synopsis of the projectThe activated cerebral cortex displays "high-conductance states" characterized intracellularly by intense subthreshold fluctuations, which are due to the high-level of activity in the local surrounding network. Present intracellular methods to characterize this activity are limited in resolution due to the bias introduced by recording electrodes. In the present project, we plan to address these limitations by proposing a new recording paradigm based on a computer-contolled feedback with the cell. Developing and implementing this paradigm will require a tight association between mathematics, computer science, computational neuroscience and intracellular electrophysiology (in vivo and in vitro). We aim at both the conception of novel methodologies, their testing in real neurons (essentially in vitro), as well as applying these methods to intracellular recordings in primary visual cortex in vivo.
The project combines different expertises, such as mathematics, computer science, computational neuroscience and intracellular electrophysiology (in vitro and in vivo), to yield accurate and reliable methods to properly characterize high-conductance states in neurons. We plan to address several of the caveats of present recording techniques, namely 1) the impossibility to perform reliable high-resolution dynamic-clamp with sharp electrodes, which is the intracellular technique mostly used in vivo; 2) the unreliability and low time resolution of single-electrode voltage-clamp recordings in vivo; 3) the impossibility of extracting single-trial conductances from Vm activity in vivo.
We propose to address these caveats with the following goals:
1. Obtain high-resolution recordings applicable to any type of electrode (sharp and patch), any type of protocol (current-clamp, voltage-clamp, dynamic-clamp) and different preparations (in vivo, in vitro, dendritic patch recordings).
2. Obtain methods to reliably extract single-trial conductances from Vm activity, as well as to "probe" the intrinsic conductances in cortical neurons. These methods will be applied to intracellular recordings during visual responses in cat V1 in vivo.
3. Obtain methods to extract correlations from Vm activity and apply these methods to intracellular recordings in vivo to measure changes in correlation in afferent activity.
4. Obtain methods to estimate spike-triggered averages from Vm activity and obtain estimates of the optimal patterns of conductances that trigger spikes in vivo.
These results will be integrated into computational models to test mechanisms for selectivity. These methods will be based on a real-time feedback between a computer and the recorded neuron. This real-time feedback will be used not only to improve existing techniques, but also to extract essential information to better understand spike selectivity of cortical neurons in vivo.
For a copy of the projet, click here.
The Active-Electrode Compensation (AEC) technique is currently under development (see Society for Neuroscience Abstracts, 31: 687.13 and 688.2, 2005; see also the summary page of the AEC). The method is described in detail in the following publications:
Recently, we published a method to extract conductance parameters from single membrane potential traces:
We also have published a method for extracting the preferred patterns of synaptic conductances linked to spike generation (spike-triggered average conductances), uniquely from the Vm activity of the recorded neuron:
Some of these methods have already been applied to in vivo and in vitro recordings:
Finally, we also have conceived methods to estimate correlations from intracellular recordings. This method was tested in vivo and in vitro; see details in:
In addition to intracellular methods, we also have proposed methods to analyze the occurrence of spike patterns in multisite recordings, and extract the correlation state of the network:
Some of the methods developed in the HR-CORTEX project constitute the basis of two review articles on the different techniques for stochastic analysis of intracellular recordings:
Unité de Neurosciences, Information & Complexité