This is a NEURON compartmental model designed to validate experimental data showing that mGluRIII activation reduces proximal and distal inhibition onto CA1 pyramidal cells (PCs) from parvalbumin and somatostatin interneurons (PV- and SST-INs, respectively). The model is implemented using the NEURON software (v8.2.0), developed in Visual Studio Code with Python (v3.10.14), and runs using the 3D morphology of a biocytin filled CA1-PCs previously developed by the Scimemi lab (PMID: 33053337). The spatial distribution of PV- and SST-inputs onto CA1-PCs is set using NRN-EZ (v1.1.7; PMID: 36627356) PV-inputs are located on the soma and <50 µm away from it on apical dendrites. SST-inputs are located at a distance of >200 um away from the soma, on apical dendrites. First, the model aims to reproduce voltage escape errors that occur when performing somatic voltage clamp recordings from CA1-PCs (folder Voltage escape). This is done by introducing a passive conductance along the dendrites, which becomes larger at increasing distance from the soma. To set the passive conductance, we randomly distribute one inhibitory synaptic input along the soma and apical dendrites of the CA1-PC. We measure the attenuation ratio for each event (i.e., local/somatic amplitude), and adjust passive conductance so that the space dependency of the attenuation ratio matches with the one obtained by using dendritic patch-clamp recordings (PMID: 18552844) and collected in prior computational work (PMID: 30835719). Second, the model is used to set the synaptic weight of inhibitory inputs onto CA1-PCs based on somatic voltage clamp recordings of mIPSCs from CA1-PCs in our own experiments (folder Set I-weight from mIPSC). Third, we reproduce the effect of mGluRIII activation on IPSCs evoked by optogenetic stimulation of PV- and SST-INs (oIPSCs; folders Effect of DHK on PV inhibition and Effect of DHK on SST inhibition).
Experimental motivation: The goal of this code is to identify the number of active inhibitory synaptic inputs that allow us to reproduce the amplitude of oIPSCs from PV- and SST-INs recorded experimentally both in control conditions and following DHK application. This was used to determine that the relative effect of mGluRIII activation on proximal and distal inhibitory synaptic signaling onto CA1 pyramidal cells.
Model Type: Neuron or other electrically excitable cell
Region(s) or Organism(s): Hippocampus; Mouse
Cell Type(s): Hippocampus CA1 pyramidal GLU cell
Currents:
Receptors: GabaA
Genes:
Transmitters: Gaba
Model Concept(s): Detailed Neuronal Models; Electrodiffusion; Synaptic Integration
Simulation Environment: NEURON; Python
Implementer(s): Dwivedi, Namit; Scimemi, Annalisa
References: