Nikolay Chenkov, ITB / BCCN / HU Berlin

Network mechanisms underlying sharp-wave ripples and memory replay

Complex patterns of neural activity appear during up-states in the neocortex and sharp-wave ripples (SWRs) in the hippocampus, including sequences that resemble those during prior behavioral
experience. The mechanisms underlying this replay are not well understood. How can small synaptic footprints engraved by experience control large-scale network activity during memory retrieval and
consolidation?

In the first part of this thesis, I hypothesise that sparse and weak synaptic connectivity between Hebbian assemblies are boosted by pre-existing recurrent connectivity within them. To investigate this idea, sequences of assemblies connected in a feedforward manner are embedded in random neural networks with a balance of excitation and inhibition. Simulations and analytical calculations show that recurrent connections within assemblies allow for a fast amplification of signals that indeed reduces the required number of inter-assembly connections. Replay can be evoked by small sensory-like cues or emerge spontaneously by activity fluctuations. Global—potentially neuromodulatory—alterations of neuronal excitability can switch between network states that favor retrieval and consolidation.

The second part of this thesis investigates the origin of the SWRs observed in in-vitro models. Recent studies have demonstrated that SWR-like events can be evoked after optogenetic stimulation of subpopulations of inhibitory neurons (Schlingloff et al., 2014; Kohus et al., 2016). To explain these results, a 3-population model is discussed as a hypothetical disinhibitory circuit that could generate the observed population bursts. The effects of pharmacological GABAergic modulators on the SWR incidence in vitro are analysed. The results are discussed in the light of the proposed disinhibitory circuit. In particular, how does gabazine, a GABAA receptor antagonist, suppress the generation of SWRs? Another explored question is whether the slow dynamics of GABAB receptors is modulating the time scale of the inter-event intervals.

Additional Information

PhD defence

Organized by

Richard Kempter