Sharp wave-ripples and interictal events are physiological and pathological forms of transient high activity
in the hippocampus with similar features. Sharp wave-ripples have been shown to be essential in memory
consolidation, while epileptiform (interictal) events are thought to be damaging. It is essential to grasp the
difference between physiological sharp wave-ripples and pathological interictal events in order to
understand the failure of control mechanisms in the latter case. We investigated the dynamics of activity
generated intrinsically in the CA3 region of the mouse hippocampus in vitro, using four different types of
intervention to induce epiletiform activity. As a result, sharp wave-ripples spontaneously occurring in CA3
disappeared, and following an asynchronous transitory phase, activity reorganized into a new form of
pathological synchrony. During epileptiform events, all neurons increased their firing rate compared to sharp
wave-ripples. Different cell types showed complementary firing: parvalbumin-positive basket cells and
some axo-axonic cells stopped firing due to a depolarization block at the climax of the events in high
potassium, 4-aminopyridine and zero magnesium models, but not in the gabazine model. In contrast,
pyramidal cells started firing maximally at this stage. To understand the underlying mechanism we
measured changes of intrinsic neuronal and transmission parameters in the high potassium model. We found
that the cellular excitability increased and excitatory transmission was enhanced, whereas inhibitory
transmission was compromised. We observed a strong short-term depression in parvalbumin-positive basket
cell to pyramidal cell transmission. Thus, the collapse of pyramidal cell perisomatic inhibition appears to be
a crucial factor in the emergence of epileptiform events
