Ictogenesis proceeds through discrete phases in hippocampal CA1 seizures in mice.

Epilepsy is characterized by spontaneous non-provoked seizures, yet the mechanisms that trigger a seizure and allow its evolution remain underexplored. To dissect out phases of ictogenesis, we evoked hypersynchronous activity with optogenetic stimulation. Focal optogenetic activation of putative excitatory neurons in the mouse hippocampal CA1 reliably evoked convulsive seizures in awake mice. A time-vs-time pulsogram plot characterized the evolution of the EEG pulse response from a light evoked response to induced seizure activity. Our results depict ictogenesis as a stepwise process comprised of three distinctive phases demarcated by two transition points. The induction phase undergoes the first transition to reverberant phase activity, followed by the second transition into the paroxysmal phase or a seizure. Non-seizure responses are confined to either induction or reverberant phases. The pulsogram was then constructed in seizures recorded from a murine model of temporal lobe epilepsy and it depicted a similar reverberance preceding spontaneous seizures. The discovery of these distinct phases of ictogenesis may offer means to abort a seizure before it develops.

DREADDs in Epilepsy Research: Network-Based Review.

Epilepsy can be interpreted as altered brain rhythms from overexcitation or insufficient inhibition. Chemogenetic tools have revolutionized neuroscience research because they allow "on demand" excitation or inhibition of neurons with high cellular specificity. Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are the most frequently used chemogenetic techniques in epilepsy research. These engineered muscarinic receptors allow researchers to excite or inhibit targeted neurons with exogenous ligands. As a result, DREADDs have been applied to investigate the underlying cellular and network mechanisms of epilepsy. Here, we review the existing literature that has applied DREADDs to understand the pathophysiology of epilepsy. The aim of this review is to provide a general introduction to DREADDs with a focus on summarizing the current main findings in experimental epilepsy research using these techniques. Furthermore, we explore how DREADDs may be applied therapeutically as highly innovative treatments for epilepsy.