"GABA is the key inhibitory neurotransmitter in the adult central nervous system, but in some circumstances can lead to a paradoxical excitation that has been causally implicated in diverse pathologies from endocrine stress responses to diseases of excitability including neuropathic pain and temporal lobe epilepsy. We undertook a computational modeling approach to determine plausible ionic mechanisms of GABAA-dependent excitation in isolated post-synaptic CA1 hippocampal neurons because it may constitute a trigger for pathological synchronous epileptiform discharge. In particular, the interplay intracellular chloride accumulation via the GABAA receptor and extracellular potassium accumulation via the K/Cl co-transporter KCC2 in promoting GABAA-mediated excitation is complex. ..."
Model Type: Neuron or other electrically excitable cell
Cell Type(s): Hippocampus CA1 pyramidal GLU cell
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; Na/Ca exchanger; Na/K pump; KCC2; NKCC1; Ca pump
Receptors: GabaA
Model Concept(s): Bursting; Detailed Neuronal Models; Epilepsy; Calcium dynamics; Markov-type model
Simulation Environment: C or C++ program
Implementer(s): Clancy, Colleen E [ceclancy at ucdavis.edu]
References:
Lewin N, Aksay E, Clancy CE. (2012). Computational modeling reveals dendritic origins of GABA(A)-mediated excitation in CA1 pyramidal neurons. PloS one. 7 [PubMed]