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CA1 network model: interneuron contributions to epileptic deficits (Shuman et al 2020)
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Accession:
256311
Temporal lobe epilepsy causes significant cognitive deficits in both humans and rodents, yet the specific circuit mechanisms underlying these deficits remain unknown. There are profound and selective interneuron death and axonal reorganization within the hippocampus of both humans and animal models of temporal lobe epilepsy. To assess the specific contribution of these mechanisms on spatial coding, we developed a biophysically constrained network model of the CA1 region that consists of different subtypes of interneurons. More specifically, our network consists of 150 cells, 130 excitatory pyramidal cells and 20 interneurons (Fig. 1A). To simulate place cell formation in the network model, we generated grid cell and place cell inputs from the Entorhinal Cortex (ECLIII) and CA3 regions, respectively, activated in a realistic manner as observed when an animal transverses a linear track. Realistic place fields emerged in a subpopulation of pyramidal cells (40-50%), in which similar EC and CA3 grid cell inputs converged onto distal/proximal apical and basal dendrites. The tuning properties of these cells are very similar to the ones observed experimentally in awake, behaving animals To examine the role of interneuron death and axonal reorganization in the formation and/or tuning properties of place fields we selectively varied the contribution of each interneuron type and desynchronized the two excitatory inputs. We found that desynchronized inputs were critical in reproducing the experimental data, namely the profound reduction in place cell numbers, stability and information content. These results demonstrate that the desynchronized firing of hippocampal neuronal populations contributes to poor spatial processing in epileptic mice, during behavior. Given the lack of experimental data on the selective contributions of interneuron death and axonal reorganization in spatial memory, our model findings predict the mechanistic effects of these alterations at the cellular and network levels.
Reference:
1 .
Shuman T, Aharoni D, Cai DJ, Lee CR, Chavlis S, Page-Harley L, Vetere LM, Feng Y, Yang CY, Mollinedo-Gajate I, Chen L, Pennington ZT, Taxidis J, Flores SE, Cheng K, Javaherian M, Kaba CC, Rao N, La-Vu M, Pandi I, Shtrahman M, Bakhurin KI, Masmanidis SC, Khakh BS, Poirazi P, Silva AJ, Golshani P (2020) Breakdown of spatial coding and interneuron synchronization in epileptic mice.
Nat Neurosci
23
:229-238
[
PubMed
]
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Model Information
(Click on a link to find other models with that property)
Model Type:
Realistic Network;
Brain Region(s)/Organism:
Hippocampus;
Cell Type(s):
Hippocampus CA1 pyramidal GLU cell;
Hippocampal CA1 CR/VIP cell;
Hippocampus CA1 axo-axonic cell;
Hippocampus CA1 basket cell;
Hippocampus CA1 basket cell - CCK/VIP;
Hippocampus CA1 stratum oriens lacunosum-moleculare interneuron ;
Hippocampus CA1 bistratified cell;
Channel(s):
I A;
I h;
I K,Ca;
I K;
I CAN;
I M;
I Sodium;
I_AHP;
I Calcium;
Gap Junctions:
Receptor(s):
AMPA;
GabaA;
GabaB;
NMDA;
Gene(s):
Transmitter(s):
Simulation Environment:
NEURON;
Brian;
Model Concept(s):
Spatial Navigation;
Implementer(s):
Chavlis, Spyridon [schavlis at imbb.forth.gr];
Pandi, Ioanna ;
Poirazi, Panayiota [poirazi at imbb.forth.gr];
Search NeuronDB
for information about:
Hippocampus CA1 pyramidal GLU cell
;
GabaA
;
GabaB
;
AMPA
;
NMDA
;
I A
;
I K
;
I M
;
I h
;
I K,Ca
;
I CAN
;
I Sodium
;
I Calcium
;
I_AHP
;
/
Shuman_et_al_2020
mechanisms
ANsyn.mod
*
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CA1 network model for place cell dynamics (Turi et al 2019)
bgka.mod
*
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CA1 network model for place cell dynamics (Turi et al 2019)
burststim2.mod
*
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CA1 network model for place cell dynamics (Turi et al 2019)
CA1 pyramidal neuron: synaptic plasticity during theta cycles (Saudargiene et al. 2015)
Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
Spine head calcium in a CA1 pyramidal cell model (Graham et al. 2014)
cad.mod
cadyn.mod
*
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CA1 network model for place cell dynamics (Turi et al 2019)
cagk.mod
*
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CA1 network model for place cell dynamics (Turi et al 2019)
CA1 pyramidal neuron: as a 2-layer NN and subthreshold synaptic summation (Poirazi et al 2003)
CA1 pyramidal neuron: dendritic Ca2+ inhibition (Muellner et al. 2015)
CA1 pyramidal neuron: synaptic plasticity during theta cycles (Saudargiene et al. 2015)
CA1 pyramidal neuron: synaptically-induced bAP predicts synapse location (Sterratt et al. 2012)
Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
cal.mod
*
Other models using cal.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
calH.mod
*
Other models using calH.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
CA1 pyramidal neuron: as a 2-layer NN and subthreshold synaptic summation (Poirazi et al 2003)
CA1 pyramidal neuron: dendritic Ca2+ inhibition (Muellner et al. 2015)
CA1 pyramidal neuron: synaptic plasticity during theta cycles (Saudargiene et al. 2015)
CA1 pyramidal neuron: synaptically-induced bAP predicts synapse location (Sterratt et al. 2012)
Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
Long time windows from theta modulated inhib. in entorhinal–hippo. loop (Cutsuridis & Poirazi 2015)
cancr.mod
*
Other models using cancr.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
car.mod
*
Other models using car.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
CA1 pyramidal neuron: as a 2-layer NN and subthreshold synaptic summation (Poirazi et al 2003)
CA1 pyramidal neuron: dendritic Ca2+ inhibition (Muellner et al. 2015)
CA1 pyramidal neuron: synaptic plasticity during theta cycles (Saudargiene et al. 2015)
CA1 pyramidal neuron: synaptically-induced bAP predicts synapse location (Sterratt et al. 2012)
Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
Long time windows from theta modulated inhib. in entorhinal–hippo. loop (Cutsuridis & Poirazi 2015)
cat.mod
*
Other models using cat.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
ccanl.mod
*
Other models using ccanl.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
CA1 pyramidal neuron: synaptic plasticity during theta cycles (Saudargiene et al. 2015)
Cell splitting in neural networks extends strong scaling (Hines et al. 2008)
Dentate gyrus (Morgan et al. 2007, 2008, Santhakumar et al. 2005, Dyhrfjeld-Johnsen et al. 2007)
Dentate gyrus network model (Santhakumar et al 2005)
Dentate gyrus network model (Tejada et al 2014)
Effects of increasing CREB on storage and recall processes in a CA1 network (Bianchi et al. 2014)
Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
Long time windows from theta modulated inhib. in entorhinal–hippo. loop (Cutsuridis & Poirazi 2015)
Parallel network simulations with NEURON (Migliore et al 2006)
State dependent drug binding to sodium channels in the dentate gyrus (Thomas & Petrou 2013)
The APP in C-terminal domain alters CA1 neuron firing (Pousinha et al 2019)
gskch.mod
*
Other models using gskch.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
h.mod
*
Other models using h.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
hha_old.mod
*
Other models using hha_old.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
CA1 pyramidal neuron: as a 2-layer NN and subthreshold synaptic summation (Poirazi et al 2003)
CA1 pyramidal neuron: dendritic Ca2+ inhibition (Muellner et al. 2015)
CA1 pyramidal neuron: synaptic plasticity during theta cycles (Saudargiene et al. 2015)
CA1 pyramidal neuron: synaptically-induced bAP predicts synapse location (Sterratt et al. 2012)
Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
Long time windows from theta modulated inhib. in entorhinal–hippo. loop (Cutsuridis & Poirazi 2015)
hha2.mod
*
Other models using hha2.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
hNa.mod
*
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CA1 network model for place cell dynamics (Turi et al 2019)
CA1 pyramidal neuron: synaptic plasticity during theta cycles (Saudargiene et al. 2015)
Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
Long time windows from theta modulated inhib. in entorhinal–hippo. loop (Cutsuridis & Poirazi 2015)
IA.mod
*
Other models using IA.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
iccr.mod
*
Other models using iccr.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
ichan2.mod
*
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CA1 network model for place cell dynamics (Turi et al 2019)
ichan2aa.mod
*
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CA1 network model for place cell dynamics (Turi et al 2019)
ichan2bc.mod
*
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CA1 network model for place cell dynamics (Turi et al 2019)
ichan2bs.mod
*
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CA1 network model for place cell dynamics (Turi et al 2019)
ichan2vip.mod
*
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CA1 network model for place cell dynamics (Turi et al 2019)
Ih.mod
*
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Active dendrites and spike propagation in a hippocampal interneuron (Saraga et al 2003)
CA1 network model for place cell dynamics (Turi et al 2019)
CA1 pyramidal neuron: synaptic plasticity during theta cycles (Saudargiene et al. 2015)
Effects of increasing CREB on storage and recall processes in a CA1 network (Bianchi et al. 2014)
Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
Long time windows from theta modulated inhib. in entorhinal–hippo. loop (Cutsuridis & Poirazi 2015)
The APP in C-terminal domain alters CA1 neuron firing (Pousinha et al 2019)
Ihvip.mod
*
Other models using Ihvip.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
ikscr.mod
*
Other models using ikscr.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
Fast Spiking Basket cells (Tzilivaki et al 2019)
Fast Spiking Basket cells (Tzilivaki et al 2019)
Pyramidal neuron, fast, regular, and irregular spiking interneurons (Konstantoudaki et al 2014)
kad.mod
*
Other models using kad.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
CA1 pyramidal neuron: as a 2-layer NN and subthreshold synaptic summation (Poirazi et al 2003)
Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
Long time windows from theta modulated inhib. in entorhinal–hippo. loop (Cutsuridis & Poirazi 2015)
kadistcr.mod
*
Other models using kadistcr.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
kap.mod
*
Other models using kap.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
Kaxon.mod
*
Other models using Kaxon.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
kca.mod
*
Other models using kca.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
Kdend.mod
*
Other models using Kdend.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
kdrcr.mod
*
Other models using kdrcr.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
Fast Spiking Basket cells (Tzilivaki et al 2019)
Fast Spiking Basket cells (Tzilivaki et al 2019)
Pyramidal neuron, fast, regular, and irregular spiking interneurons (Konstantoudaki et al 2014)
km.mod
*
Other models using km.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
Ksoma.mod
*
Other models using Ksoma.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
LcaMig.mod
*
Other models using LcaMig.mod:
Basket cell extrasynaptic inhibition modulates network oscillations (Proddutur et al., 2013)
CA1 network model for place cell dynamics (Turi et al 2019)
CA1 pyramidal neuron: synaptic plasticity during theta cycles (Saudargiene et al. 2015)
Cell splitting in neural networks extends strong scaling (Hines et al. 2008)
Dentate gyrus (Morgan et al. 2007, 2008, Santhakumar et al. 2005, Dyhrfjeld-Johnsen et al. 2007)
Dentate gyrus network model (Santhakumar et al 2005)
Dentate gyrus network model (Tejada et al 2014)
Effects of increasing CREB on storage and recall processes in a CA1 network (Bianchi et al. 2014)
Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
Long time windows from theta modulated inhib. in entorhinal–hippo. loop (Cutsuridis & Poirazi 2015)
Parallel network simulations with NEURON (Migliore et al 2006)
State dependent drug binding to sodium channels in the dentate gyrus (Thomas & Petrou 2013)
Status epilepticus alters dentate basket cell tonic inhibition (Yu J et al 2013)
The APP in C-terminal domain alters CA1 neuron firing (Pousinha et al 2019)
my_exp2syn.mod
*
Other models using my_exp2syn.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
Naaxon.mod
*
Other models using Naaxon.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
Nadend.mod
*
Other models using Nadend.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
nafcr.mod
*
Other models using nafcr.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
Fast Spiking Basket cells (Tzilivaki et al 2019)
Fast Spiking Basket cells (Tzilivaki et al 2019)
Pyramidal neuron, fast, regular, and irregular spiking interneurons (Konstantoudaki et al 2014)
nap.mod
*
Other models using nap.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
Nasoma.mod
*
Other models using Nasoma.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
nca.mod
*
Other models using nca.mod:
Basket cell extrasynaptic inhibition modulates network oscillations (Proddutur et al., 2013)
CA1 network model for place cell dynamics (Turi et al 2019)
CA1 pyramidal neuron: synaptic plasticity during theta cycles (Saudargiene et al. 2015)
Cell splitting in neural networks extends strong scaling (Hines et al. 2008)
Dentate gyrus network model (Santhakumar et al 2005)
Dentate gyrus network model (Tejada et al 2014)
Effects of increasing CREB on storage and recall processes in a CA1 network (Bianchi et al. 2014)
Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
Long time windows from theta modulated inhib. in entorhinal–hippo. loop (Cutsuridis & Poirazi 2015)
Parallel network simulations with NEURON (Migliore et al 2006)
State dependent drug binding to sodium channels in the dentate gyrus (Thomas & Petrou 2013)
Status epilepticus alters dentate basket cell tonic inhibition (Yu J et al 2013)
The APP in C-terminal domain alters CA1 neuron firing (Pousinha et al 2019)
nmda.mod
*
Other models using nmda.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
regn_stim.mod
*
Other models using regn_stim.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
somacar.mod
*
Other models using somacar.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
STDPE2Syn.mod
*
Other models using STDPE2Syn.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
CA1 pyramidal neuron: synaptic plasticity during theta cycles (Saudargiene et al. 2015)
Encoding and retrieval in a model of the hippocampal CA1 microcircuit (Cutsuridis et al. 2009)
vecstim.mod
*
Other models using vecstim.mod:
CA1 network model for place cell dynamics (Turi et al 2019)
Fast Spiking Basket cells (Tzilivaki et al 2019)
Fast Spiking Basket cells (Tzilivaki et al 2019)
L5 PFC microcircuit used to study persistent activity (Papoutsi et al. 2014, 2013)
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