Compartmentalization of GABAergic inhibition by dendritic spines (Chiu et al. 2013)

 Download zip file   Auto-launch 
Help downloading and running models
Accession:143604
A spiny dendrite model supports the hypothesis that only inhibitory inputs on spine heads, not shafts, compartmentalizes inhibition of calcium signals to spine heads as seen in paired inhibition with back-propagating action potential experiments on prefrontal cortex layer 2/3 pyramidal neurons in mouse (Chiu et al. 2013).
Reference:
1 . Chiu CQ, Lur G, Morse TM, Carnevale NT, Ellis-Davies GC, Higley MJ (2013) Compartmentalization of GABAergic inhibition by dendritic spines. Science 340:759-62 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Synapse; Dendrite;
Brain Region(s)/Organism: Neocortex;
Cell Type(s): Neocortex L2/3 pyramidal GLU cell;
Channel(s): I Na,t; I L high threshold; I K;
Gap Junctions:
Receptor(s): GabaA;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Dendritic Action Potentials; Influence of Dendritic Geometry;
Implementer(s): Carnevale, Ted [Ted.Carnevale at Yale.edu]; Morse, Tom [Tom.Morse at Yale.edu];
Search NeuronDB for information about:  Neocortex L2/3 pyramidal GLU cell; GabaA; I Na,t; I L high threshold; I K;
Miscellaneous model details:

1) The two starting cases can be controlled by pushing one of two
buttons in the "Morphology and Spine neck resistivity" control panel
about a third of the way up from the bottom:

a) dendrite diam=2 (look for the diam2_dendrite_gbar_ca)

This is the original dendrite length and ion channels max conductance
configuration for the paper.  The Na and K excitability (maximum
conductances) were raised to a level comfortably above where reliably
propagated bAPs occur (When the conductace is lowered by multiplying
by 0.4 the bAPs decrement as they propagate.  Starting from a
multiplying "factor=0.5" in an init.hoc morpohology control panel,
lowering to "factor=0.2" accomplishes this .4 drop ).  The calcium
maximum conductances were set to where a single bAP accumulated a peak
of 1 uM Ca (suggested by Higley) in an uninhibited spine head.  The
calcium currents do not significantly effect the voltage trajectory so
this setting is arbitrary in regards to the voltage trace.

b) dendrite diam=.7 (look for the diamp7_dendrite_gbar_ca)

The same statements under a) above apply except that the K density
(K_DR mechanism "kv") was boosted to counteract additional excitability of
smaller sized membrane which fires a chain of APs in the chloride
reversal potential = -40 mV numerical experiment.  (The real
experiments do not have a train of APs in this case).

---

On the length of the dendrite choice:

We use the dendrite L=600 micron version to avoid bAP peaks growing
per distance from the soma (confounding the studies of inhibition) as
occur in the L=200 case.  In L=200 the bAP peaks grow as they
propagate through the distances that the spines are placed, close to
the end of the cylinder.  We assume in the real neurons decreasing
sodium channels or increasing K channels likely maintain constant
height of bAPs as they propagate since experimentally the peak Ca
signals in spines are distance independent (Figure S3c).  We could
have used maximum conductances that varied as a function of distance
in the model instead of the longer dendrite.

---

The supplemental graph panels show changes in the activation of ca
(vertical) and changes in the reversal potential of gabaa (horizontal)
effects on inhibition of Ca signals in spines.

-------

To calculate the 5 conditions for active and passive spines:
1) click the multiconditions button
2) copy the multiconditions folder
cp -r multiconditions multiconditions_pas_spine
3) click the make spines active button
4) click the multiconditions button
5) copy the multiconditions folder
cp -r multiconditions multiconditions_act_spine
6) run matlab program matlab/dCa_ratio.m

-------


Loading data, please wait...