Seizures as imbalanced up states: Excitatory and inhibitory conductances during seizure-like events

Precisely timed and dynamically balanced excitatory (E) and inhibitory (I) conductances underlie the basis of neural network activity. Normal E/I balance is often shifted in epilepsy, resulting in neuronal network hyperexcitability and recurrent seizures. However, dynamics of the actual excitatory and inhibitory synaptic conductances (g_e and g_i, respectively) during seizures remain unknown. To study the dynamics of E and I network balance, we calculated g_e and g_i during the initiation, body, and termination of seizure-like events (SLEs) in the rat hippocampus in vitro. Repetitive emergent SLEs in 4-aminopyridine (100 μM) and reduced extracellular magnesium (0.6 mM) were recorded in the identified CA1 pyramidal cells (PC) and oriens-lacunosum moleculare (O-LM) interneurons. Calculated g_e/g_i ratio dynamics showed that the initiation stage of the SLEs was dominated by inhibition in the PCs and was more balanced in the O-LM cells. During the body of the SLEs, the balance shifted toward excitation, with g_e and g_i peaking in both cell types at nearly the same time. In the termination phase, PCs were again dominated by inhibition, whereas O-LM cells experienced persistent excitatory synaptic barrage. In this way, increased excitability of interneurons may play roles in both seizure initiation (Žiburkus J, Cressman JR, Barreto E, Schiff SJ. J Neurophysiol 95: 3948-3954, 2006) and in their termination. Overall, SLE stages can be characterized in PC and O-LM cells by dynamically distinct changes in the balance of g_e and g_i, where a temporal sequence of imbalance shifts with the changing firing patterns of the cellular subtypes comprising the hyperexcitable microcircuits.