/157157

CA1 pyramidal neuron: synaptic plasticity during theta cycles (Saudargiene et al. 2015)

Primary LanguageAMPL

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This is the readme for the model associated with the paper:

Saudargiene A, Cobb S, Graham BP.
A computational study on plasticity during theta cycles at Schaffer 
collateral synapses on CA1 pyramidal cells in the hippocampus.
Hippocampus 2015;25(2):208-218. 

This NEURON code implements a microcircuit of CA1 pyramidal neuron and
consists of a detailed model of CA1 pyramidal cell and four types of
inhibitory interneurons (basket, bistratified, axoaxonic and oriens
lacunosum-moleculare cells). Synaptic plasticity during theta cycles
at a synapse in a single spine on the stratum radiatum dendrite of the
CA1 pyramidal cell is modeled using a phenomenological model of
synaptic plasticity (Graupner and Brunel, 2012).

The code is adapted from the Poirazi CA1 pyramidal cell (ModelDB
accession number 20212) and the Cutsuridis microcircuit model (ModelDB
accession number 123815)

Abstract:

Cellular activity in the CA1 area of the hippocampus waxes and wanes
at theta frequency (4-8Hz) during exploratory behaviour of
rats. Perisomatic inhibition onto pyramidal cells tends to be
strongest out of phase with pyramidal cell activity, whereas dendritic
inhibition is strongest in phase with pyramidal cell
activity. Synaptic plasticity also varies across the theta cycle, from
strong long-term potentiation (LTP) to long-term-depression (LTD),
putatively corresponding to encoding and retrieval phases for
information patterns encoded by pyramidal cell activity (Hasselmo et
al, 2002a). The mechanisms underpinning the phasic changes in
plasticity are not clear, but it is likely that inhibition plays a
role by affecting levels of electrical activity and calcium
concentration at synapses. We explore the properties of synaptic
plasticity at Schaffer collateral synapses on CA1 pyramidal neurons
and the influence of spatially and temporally targeted inhibition
using a detailed multicompartmental model of the CA1 pyramidal neuron
microcircuit and a phenomenological model of synaptic plasticity. The
results suggest CA3-CA1 synapses are potentiated on one phase of theta
due to high calcium levels provided by paired weak CA3 and layer III
entorhinal cortex (EC) inputs even when somatic spiking is inhibited
by perisomatic interneuron activity. Weak CA3 inputs alone induce
lower calcium transients and result in depression of the CA3-CA1
synapses. These synapses are depressed if activated in phase with
dendritic inhibition as strong CA3 inputs alone are not able to cause
high calcium in this theta phase even though the CA1 pyramidal neuron
shows somatic spiking. Dendritic inhibition acts as a switch that
prevents LTP and promotes LTD during the retrieval phases of the theta
rhythm in CA1 pyramidal cell. This may be important for not overly
reinforcing recalled memories and in forgetting no longer relevant
memories.

Main file: main.hoc 

This file reproduces data presented in figures 2-5 of the paper.  The
parameters of the simulation protocol are defined by the index
ind_simulation.  Calcium concentration and synaptic efficacy variables
in a SR spine start evolving at t=250ms to allow a network to fully
establish its activity.  Data is written in the files (* indicates the
index of the simulation protocol): results_exp*.dat rasterCA3_exp*.dat
rasterEC_exp*.dat

Usage:
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Auto-launch the model from ModelDB (if your browser is configured for
this) or download and extract these files, compile the mod files (with
nrnivmodl, (unix/linux) or mknrndll (mac/windows)). For more help on
running the model see
<a href="https://senselab.med.yale.edu/ModelDB/NEURON_DwnldGuide.html">https://senselab.med.yale.edu/ModelDB/NEURON_DwnldGuide.html</a>

Under unix/linux start the simulation with command
nrngui mosinit.hoc

Under windows double click the mosinit.hoc file

Under mac os X either use the unix/linux instructions or drag and drop
the mosinit.hoc to the nrngui icon.

Once the simulation starts it will run with ind_simulation=1 which
corresponds to figure 2 in the paper. It takes 7 minutes to generate on a
2012 macbook pro (or 5 1/2 minutes if you hide (click hide on) the
figures while it is running):

<img src="./screenshot.png" alt="screenshot" width="550">

Changelog:
----------
2022-05: Updated MOD files to contain valid C++ and be compatible with
         the upcoming versions 8.2 and 9.0 of NEURON.
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