" ...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."
Model Type: Realistic Network
Region(s) or Organism(s): 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
Currents: 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
Model Concept(s): Epilepsy
Simulation Environment: FORTRAN
Implementer(s): Traub, Roger D [rtraub at us.ibm.com]
References:
Hall S et al. (2015). Unbalanced Peptidergic Inhibition in Superficial Neocortex Underlies Spike and Wave Seizure Activity. The Journal of neuroscience : the official journal of the Society for Neuroscience. 35 [PubMed]