The pathophysiology of sleep-dependent memory consolidation
Final Report Abstract
A dialogue between the hippocampus and neocortex constitutes the physiological basis of sleepdependent memory consolidation. The hippocampus also reflects a predilection site for epilepsy - a network disorder characterized by impaired memory retention and an imbalance between excitation and inhibition (E/I-balance) at the neuronal level that generates interictal epileptiform discharges (IEDs) and seizures. Critically, IEDs preferentially occur during non-rapid-eyemovement (NREM) sleep that facilitates hippocampal-neocortical interactions and memory formation in the healthy brain. Hence, E/I-imbalance, IEDs, and impaired network interactions might be fundamental causes of memory impairments in patients with epilepsy. This project utilized E/I-balance as a unifying framework to investigate the intricate three-way interactions between sleep, memory, and epilepsy in patients with epilepsy. Here, I showed that EEG aperiodic activity as quantified by the spectral slope indexes excitability dynamics at the mesoscale as determined using calcium imaging in rodents. I subsequently showed that hyperexcitability during seizures can be characterized by a flattening of the spectral slope, potentially constituting a clinically-relevant marker of pathologic activity. Finally, my results provide novel insights into the hippocampal-neocortical interactions during sleep underlying memory consolidation processes. The results show how ripples from the prefrontal cortex are functionally distinct from their archicortical counterparts. These results describe an evolutionarily-preserved mechanism where the precisely coordinated interplay between hippocampal and neocortical ripples temporally segregates hippocampal information transfer from subsequent neocortical processing during sleep. Combined, these studies provide novel insights into network dynamics that establish or disrupt the neuronal balance between excitation and inhibition, and show how newly established cortical ripples contribute to the hippocampal-neocortical dialogue that facilitates sleep-dependent memory consolidation.
Publications
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An evolutionary conserved division-of-labor between archicortical and neocortical ripples organizes information transfer during sleep. Progress in Neurobiology, 227, 102485.
van Schalkwijk, Frank J.; Weber, Jan; Hahn, Michael A.; Lendner, Janna D.; Inostroza, Marion; Lin, Jack J. & Helfrich, Randolph F.
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Human REM sleep recalibrates neural activity in support of memory formation. Science Advances, 9(34).
Lendner, Janna D.; Niethard, Niels; Mander, Bryce A.; van Schalkwijk, Frank J.; Schuh-Hofer, Sigrid; Schmidt, Hannah; Knight, Robert T.; Born, Jan; Walker, Matthew P.; Lin, Jack J. & Helfrich, Randolph F.
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The effects of slow wave sleep characteristics on semantic, episodic, and procedural memory in people with epilepsy. Frontiers in Pharmacology, 15.
Höller, Yvonne; Eyjólfsdóttir, Stefanía; Van Schalkwijk, Frank Jasper & Trinka, Eugen
