Physiological sharp wave-ripples and interictal events in vitro: what's the difference?

• Published in: Brain (London, England : 1878) Vol. 137; no. Pt 2; pp. 463 - 485
• Main Authors: MARIA, R. Karlócai, ZSOLT, Kohus, SZABOLCS, Káli, ISTVAN, Ulbert, GABOR, Szabó, ZOLTAN, Máté, TAMAS, F. Freund, ATTILA, I. Gulyás
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-02-2014
• Subjects: Action Potentials - physiology; Animals; Biological and medical sciences; CA3 Region, Hippocampal - cytology; CA3 Region, Hippocampal - physiology; Electrodiagnosis. Electric activity recording; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Memory - physiology; Mice; Mice, Transgenic; Nervous system; Nervous system (semeiology, syndromes); Neurology; Neurons - physiology; Organ Culture Techniques; Pyramidal Cells - physiology; Depolarization; depolarization block; Nervous system diseases; Epilepsy; Central nervous system disease; inhibitory cells; synchronous events; Cerebral disorder; sharp wave-ripples; epilepsy
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awt348

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, whereas epileptiform (interictal) events are thought to be damaging. It is essential to grasp the difference between physiological sharp wave-ripples and pathological interictal events to understand the failure of control mechanisms in the latter case. We investigated the dynamics of activity generated intrinsically in the Cornu Ammonis region 3 of the mouse hippocampus in vitro, using four different types of intervention to induce epileptiform activity. As a result, sharp wave-ripples spontaneously occurring in Cornu Ammonis region 3 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 as a result of 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 began 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.