Unbalanced peptidergic inhibition in superficial cortex underlies seizure activity (Hall et al 2015)

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Accession:235768
" ...Loss of tonic neuromodulatory excitation, mediated by nicotinic acetylcholine or serotonin (5HT3A) receptors, of 5HT3-immunopositive interneurons caused an increase in amplitude and slowing of the delta rhythm until each period became the "wave" component of the spike and wave discharge. As with the normal delta rhythm, the wave of a spike and wave discharge originated in cortical layer 5. In contrast, the "spike" component of the spike and wave discharge originated from a relative failure of fast inhibition in layers 2/3-switching pyramidal cell action potential outputs from single, sparse spiking during delta rhythms to brief, intense burst spiking, phase-locked to the field spike. The mechanisms underlying this loss of superficial layer fast inhibition, and a concomitant increase in slow inhibition, appeared to be precipitated by a loss of neuropeptide Y (NPY)-mediated local circuit inhibition and a subsequent increase in vasoactive intestinal peptide (VIP)-mediated disinhibition. Blockade of NPY Y1 receptors was sufficient to generate spike and wave discharges, whereas blockade of VIP receptors almost completely abolished this form of epileptiform activity. These data suggest that aberrant, activity-dependent neuropeptide corelease can have catastrophic effects on neocortical dynamics."
Reference:
1 . Hall S, Hunt M, Simon A, Cunnington LG, Carracedo LM, Schofield IS, Forsyth R, Traub RD, Whittington MA (2015) Unbalanced Peptidergic Inhibition in Superficial Neocortex Underlies Spike and Wave Seizure Activity. J Neurosci 35:9302-14 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Neocortex; Thalamus;
Cell Type(s): Thalamus geniculate nucleus/lateral principal GLU cell; Thalamus reticular nucleus GABA cell; Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell; Neocortex U1 L6 pyramidal corticalthalamic GLU cell; Neocortex fast spiking (FS) interneuron; Neocortex spiking regular (RS) neuron; Neocortex spiking low threshold (LTS) neuron;
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; I A, slow;
Gap Junctions: Gap junctions;
Receptor(s): GabaA; AMPA; NMDA;
Gene(s):
Transmitter(s):
Simulation Environment: FORTRAN;
Model Concept(s): Epilepsy;
Implementer(s): Traub, Roger D [rtraub at us.ibm.com];
Search NeuronDB for information about:  Thalamus geniculate nucleus/lateral principal GLU cell; Thalamus reticular nucleus GABA cell; Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell; Neocortex U1 L6 pyramidal corticalthalamic GLU cell; GabaA; AMPA; NMDA; 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; I A, slow;
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HallEtAl2015
readme.html
dexptablebig_setup.f *
dexptablesmall_setup.f *
fnmda.f *
groucho_gapbld.f *
groucho_gapbld_mix.f *
integrate_deepaxaxx.f *
integrate_deepbaskx.f *
integrate_deepLTSx.f *
integrate_deepng.f *
integrate_nontuftRSXXB.f *
integrate_nrtxB.f *
integrate_spinstelldiegoxB.f *
integrate_supaxaxx.f *
integrate_supbaskx.f *
integrate_supLTSX.f *
integrate_supng.f *
integrate_suppyrFRBxPB.f *
integrate_suppyrRS.f *
integrate_suppyrRS[1].f *
integrate_suppyrRSXPB.f *
integrate_tcrxB.f *
integrate_tuftIBVx3B.f *
integrate_tuftRSXXB.f *
makefile *
otis_table_setup.f *
spikewaveS1.pdf
spikewaveS1.png
spikewaveS5.f *
spikewaveS5.pdf
spikewaveS5.png
synaptic_compmap_construct.f *
synaptic_map_construct.f *
                            
            SUBROUTINE synaptic_map_construct (thisno,
     &    num_presynaptic_cells, num_postsynaptic_cells,
     &    map, num_presyninputs_perpostsyn_cell, display) 

c Construct a map of presynaptic cells of one type to postsyn.
c  cells of some type. 
c display is an integer flag.  If display = 1, print gjtable

        INTEGER thisno, num_presynaptic_cells,
     &   num_postsynaptic_cells,
     &   num_presyninputs_perpostsyn_cell,
     &   map (num_presyninputs_perpostsyn_cell,
     &          num_postsynaptic_cells) 
        INTEGER i,j,k,l,m,n,o,p
        INTEGER display

        double precision seed, x(1)

            seed = 297.d0
            map = 0
            k = 1

        do i = 1, num_postsynaptic_cells
        do j = 1, num_presyninputs_perpostsyn_cell
            call durand (seed, k, x)
c This defines a presynaptic cell

           L = int ( x(1) * dble (num_presynaptic_cells) )
           if (L.eq.0) L = 1
           if (L.gt.num_presynaptic_cells)
     &           L = num_presynaptic_cells

           map (j,i) = L

        end do
        end do

c Possibly print out map when done.
       if ((display.eq.1).and.(thisno.eq.0)) then
        write (6,800)               
800     format('  SYNAPTIC MAP ')
        do i = 1, num_postsynaptic_cells
         write (6,50) map(1,i), map(2,i),
     &        map(num_presyninputs_perpostsyn_cell,i)               
50       FORMAT(3i6)
        end do
       endif

                 END

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