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Cellular and Network Mechanisms Underlying the Switch Between Hippocampal Oscillatory States

Geschwill, Pascal

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Abstract

Local field potentials in the hippocampus are dominated by two different activity patterns - persistent gamma band (30-60Hz) oscillations and intermittent sharp wave-ripple (200Hz) complexes. The former are associated with exploratory behaviours in which information is acquired while the latter are believed to be involved in transfer and consolidation of information to long-term memory. Although there is a great wealth of knowledge about how neuronal networks maintain each oscillatory state, it is not entirely clear what cellular mechanisms mediate the switch between gamma to sharp wave-ripple activity. The goal of this thesis was to characterise this transition at the network and synaptic level. To this end, an \textit{in vitro} model based on acute hippocampal slices was established in which both gamma rhythms and sharp wave-ripples could be evoked. This was achieved with a custom-built holographic illumination system granting targeted and selective optogenetic stimulation of pyramidal cells. Prolonged stimulation of the reduced hippocampal slice network elicited self-synchronisation to a gamma rhythm (50Hz) with a resonance at theta frequency inputs (i.e. 4-5Hz sinusoidal stimulation). This frequency preference was confirmed at the single unit level which revealed most precise coordination of single cell activity within the ongoing gamma rhythm at theta frequency inputs. Additionally, evoked gamma synchronisation emerged suddenly 200ms after stimulus onset indicating a near instantaneous switch of hippocampal network states. This finding was reflected in whole-cell recordings of postsynaptic currents which displayed a sharp increase in both excitatory and inhibitory inputs around 200-300ms after stimulus onset. On the other hand, applying short (5ms) square pulses of low intensity stimulation evoked local field potential signatures closely resembling sharp wave-ripples. This implies that stimulus duration and profile are critical determinants of network output. The results presented here provide experimental evidence for prevailing models of different hippocampal network oscillations and extend the knowledge about how neuronal networks can maintain different oscillatory states and how the transition between these states is brought about.

Item Type: Dissertation
Supervisor: Draguhn, Prof. Dr. Andreas
Date of thesis defense: 29 September 2017
Date Deposited: 06 Oct 2017 10:14
Date: 2017
Faculties / Institutes: The Faculty of Bio Sciences > Dean's Office of the Faculty of Bio Sciences
Medizinische Fakultät Heidelberg > Institut fuer Physiologie und Pathophysiologie
Subjects: 500 Natural sciences and mathematics
570 Life sciences
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