CA1 pyramidal neuron: as a 2-layer NN and subthreshold synaptic summation (Poirazi et al 2003)

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Accession:20212
We developed a CA1 pyramidal cell model calibrated with a broad spectrum of in vitro data. Using simultaneous dendritic and somatic recordings, and combining results for two different response measures (peak vs. mean EPSP), two different stimulus formats (single shock vs. 50 Hz trains), and two different spatial integration conditions (within vs. between-branch summation), we found the cell's subthreshold responses to paired inputs are best described as a sum of nonlinear subunit responses, where the subunits correspond to different dendritic branches. In addition to suggesting a new type of experiment and providing testable predictions, our model shows how conclusions regarding synaptic arithmetic can be influenced by an array of seemingly innocuous experimental design choices.
References:
1 . Poirazi P, Brannon T, Mel BW (2003a) Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell. Neuron 37:977-987 [PubMed]
2 . Poirazi P, Brannon T, Mel BW (2003b) Pyramidal Neuron as Two-Layer Neural Network. Neuron 37:989-999 [PubMed]
3 . Poirazi P, Brannon T, Mel BW (2003ab-sup) Online Supplement: About the Model Neuron 37 Online:1-20
4 . Polsky A, Mel BW, Schiller J (2004) Computational subunits in thin dendrites of pyramidal cells. Nat Neurosci 7:621-7 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Hippocampus CA1 pyramidal cell;
Channel(s): I Na,p; I Na,t; I L high threshold; I T low threshold; I A; I K; I M; I h; I K,Ca; I Calcium;
Gap Junctions:
Receptor(s): GabaA; GabaB; NMDA; Glutamate;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Activity Patterns; Dendritic Action Potentials; Active Dendrites; Influence of Dendritic Geometry; Detailed Neuronal Models; Action Potentials; Depression; Delay;
Implementer(s): Poirazi, Panayiota [poirazi at imbb.forth.gr];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; GabaA; GabaB; NMDA; Glutamate; I Na,p; I Na,t; I L high threshold; I T low threshold; I A; I K; I M; I h; I K,Ca; I Calcium;
See note at bottom for version information.

This directory contains the Neuron code for the CA1 pyramidal cell model and the experiments described in
1. Poirazi P, Brannon T, Mel BW (2003a) Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell. Neuron 37:977-987
2. Poirazi P, Brannon T, Mel BW (2003b) Pyramidal Neuron as Two-Layer Neural Network. Neuron 37:989-999
3. Poirazi P, Brannon T, Mel BW (2003ab-sup) Online Supplement: About the Model Neuron 37 Online:1-20



FOR DETAILED INFORMATION ABOUT THE MODEL DISCRIPTION SEE Detailed Model Description

Following is a brief overview of the contents of this directory:

(1) lib: 		This directory contains all the library functions called
			in the setup of the CA1 model cell as well as functions used in
			the experiments. Each of the functions is described in detail
			within the respective *.hoc file. 

(2) morphology: 	This directory contains the morphology of the cell
			as well as various lists of dendritic compartments used in the
			model setup and the experiments (files are in subdirectory n123).
			
(3) template:		This directory contains a few files that define
			templates used in the model setup and experiments. Templates
			are described in the .hoc files. 

(4) experiment: 	This directory contains a selected set of experiments as described 
			in the aforementioned publications. Within each subdirectory, the 
			*.hoc files contain the NEURON code for the experiment while the 
			run_* files are the executables used by the user to run the experiment. 
			Each experiment is described in detail in the respective .hoc files. Briefly:
			
			

tune-synapses		%%%% Code for tuning the AMPA/NMDA conductances of a synapse placed on any possible location
			%%%% of the cell such that a local single pulse stimulation will result in 5mV local depolarization
			%%%% For tuning, the NMDA conductance for each position is calculated using the NMDA/AMPA ratio 
			%%%% parameter provided by the user in /morphology/n123/nmda-ampa-ratio.hoc

spike-train-attennuation
			%%%% Code for (1) Backpropagating Action Potential generation (bpap.hoc) with somatic or dendritic 
			%%%% stimulation and (2) somatic/dendritic single trace generation under control, A-current blockade and
			%%%% Ca++ current blockade (Hofman_traces.hoc). The aim of this experiment is (1) to ensure that BPAPs 
			%%%% behave similarly to biophysical data that differentiate between somatic and dendritic stimulation 
			%%%% as seen in Spruston et al, 1995 and Golding eta al 1999. (2) to ensure that cell response to 
			%%%% short stimuli under control, A-current and A,Ca++-current blockade resemble biophysical
			%%%% data provided by Hofman et al 1997. The experiment is used to generate figure 2 in Poirazi,P. 
			%%%% Brannon, T. and Mel, B.W. 'Online Supplement: About the Model.'
hyperpolarization-current	
			%%%% This experiment is used to study the effect of h-current on (1) input resistances and 
			%%%% (2) propagation of hyperpolarizing voltage traces at the somatic and dendritic regions 
			%%%% and to ensure that model responses comply with physiological findings provided by Magee 1998.
			%%%% The experiment is used to generate figure 1 in Poirazi,P. Brannon, T. and Mel, B.W. 
			%%%% 'Online Supplement: About the Model.'
			
single-shock		%%%% This directory contains code for the Cash and Yuste 1999 validation experiments shown in Poirazi,P. 
			%%%% Brannon, T. and Mel, B.W. 'Arithmetic of Subthreshold Synaptic Summation in a Model CA1 Pyramidal Cell., figures 1 and 2.
			%%%% It includes code for single pulse stimulation of two synaptic stimuli (a) individually and (b) in combination. 
			%%%% The stimuli are placed on either one or two trunk sections (Trunk_A.hoc, Trunk_AplusB.hoc) or within a single oblique dendrite
			%%%% (Apical_Tips.hoc). The aim of this experiment is to show that the model cell performs the same kind
			%%%% of synaptic integration for single pulse stimuli as the Cash and Yuste 1999 paper shows.


single-branch-potency   %%%% This directory contains code for the generation of figures 3 and 4 in Poirazi,P. Brannon, T. and Mel, B.W.
			%%%% 'Arithmetic of Subthreshold Synaptic Summation in a Model CA1 Pyramidal Cell. as well as figure 3 in Poirazi,P. Brannon, T. 
			%%%% and Mel, B.W. 'Pyramidal Neuron as 2-Layer Neural Network.' This includes code for 50Hz
			%%%% or single shock stimulation of two groups of synapses in apical obliques where synapses are stimulated 
			%%%% (a) individually and (b) in combination. Stimulated synapses can be within the same oblique (A_feq.hoc, A+Bfreq.hoc, A_shock.hoc
			%%%% A+Bfreq.hoc) or in two different obliques (A+Cfreq.hoc, A+Cshock.hoc). The aim of this experiment is to show
			%%%% that synaptic integration is different for single pulse vs high frequency stimulation and for within versus between
			%%%% side branch stimulation.


cluster-dispersion      %%%% This directory contains code for the generation of figures 2, 5 and 6 in Poirazi,P. Brannon, T. and Mel, B.W. 
			%%%% 'Arithmetic of Subthreshold Synaptic Summation in a Model CA1 Pyramidal Cell.' This includes code for 50 Hz stimulation 
			%%%% of a fixed number of excitatory synapses (32, 35, 36, 40, 45, 48, 49 or 63) which are distributed on apical 
			%%%% obliques in increasingly clustered form. In some cases, inhibition is added to prevent uncontrolled spiking.
			%%%% Spike rate for different degrees of synaptic clustering, synchronicity and background activation.
			%%%% (Disperse_equal_sized.hoc, Disperse_equal_sized_tuft.hoc, Disperse_6_2.hoc) is used to validate a mathematical model that 
			%%%% predicts cell firing rate for various synaptic stimuli (figures 5 & 6).


Within each experiment directory, the *.hoc files contain the code to be executed and the respective run* files are the executables.
The user need to turn these files into executables by using the command:

chmod +x run_Afreq

on a unix/linux prompt, in the specific experiment directory. Then to run the experiments the user needs to
type the run* file name on the unix promt and assuming the NEURON path is set correctly in his/her .bashrc file
the experiments should start running.

!!!Clarification change!!!: The conductance value for the h current has been scaled by a factor of 1000 in cell-setup.hoc in order to eliminate this scaling 
factor from the h.mod file and correct the reported value which appeared to be very high in the Online Supplement. This does not alter the current in the 
model at all. The correction is in the reported conductance value which becomes 0.1872 mS/cm^2 and not 18.72 mS/cm^2 as was reported in the Online Supplement.


!!! Bug Report !!!  There was a typo in the nap.mod file pointed out by Michele Migliore which has now been corrected. It did not appear to have any significant 
effect on the model behavior and results.



If you have any problems using the model, please feel free to
contact me at poirazi@imbb.forth.gr.

Hope this is helpful! Good luck,

Yiota Poirazi
December 4th, 2003


-------
6/22/2004 Version: In addition to the above bug report, these files were modified to run on mswin and 
updated to work with the very most recent (alpha version) of NEURON (request a replacement mos2nrn1.sh if you
want to autolaunch this model on mswin or install the alpha version
ftp://www.neuron.yale.edu/neuron/versions/alpha/nrn5.7.10setup.exe
available from neuron web site.)
If you have an earlier 5.x version of neuron on mswin you can use these files by 
by cd'ing to the mechanisms directory and compiling the mod files there and then starting up 
mosinit.hoc in the mechanisms directory (double clicking in mswin).
20120112 Version: the euler methods in cad.mod and gabab.mod were updated to
derivimplicit and cnexp as per
http://www.neuron.yale.edu/phpbb/viewtopic.php?f=28&t=592

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