Figure 2.

Molecular, cellular, and circuit mechanisms of SDL. A model of SDL based on activation of extrasynaptic GABA_AR on hippocampal dentate gyrus interneurons [28**]. (A) Conditions reflecting normal tonic inhibition (thin red arrow) allow for activation of some excitatory granule cells and induce changes of local network activity as well as coherent activity between the hippocampus and its cortical and subcortical targets. These changes are correlated with successful memory retrieval in a contextual fear conditioning paradigm, revealed as freezing behavior during a memory test. (B) Increasing tonic inhibition via extrasynaptic GABA_AR (thick red arrow) on interneurons increases the number of active granule cells via disinhibition, and induces changes of local and global oscillatory activities. This results in disrupted hippocampal-cortical and enhanced hippocampal subcortical processing of context memories. Such memories are best retrieved when extrasynaptic GABA_AR are reactivated, recreating the state at encoding. KCC2, chloride symporter.