TY  - GEN
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/24508/
Y1  - 2018///
ID  - heidok24508
TI  - Formation and Modulation of Hippocampal Ensemble Activity
AV  - public
A1  - Kaiser, Martin Erich
KW  - Sharp wave-ripple oscillations
Gamma oscillations
N2  - The extent to which advanced organisms can grasp and learn complex environmental patterns
represents a fascinating feature. It is believed that memory is encoded by transiently
co-active cells, so called neuronal ensembles, in which cells are temporally linked by underlying
network oscillations. In the hippocampus, rhythms of oscillating neuronal networks
are directly associated with behavioral states. For instance, gamma rhythms are linked
to memory formation, whereas intermittent sharp wave-ripple oscillations are involved in
memory consolidation.
During coordinated neuronal ensemble activity participating cells are selectively activated
although they are scattered throughout neuronal tissue. This spatiotemporal specificity
requires dynamic anatomical and physiological working principles. In this work, we aimed
for a deeper understanding of the apparent complexity underlying neuronal ensemble formation.
We studied the recruitment of single cells into neuronal ensembles during sharp
wave-ripple oscillations in vitro. In our approach, we combined recent physiological and
anatomical evidence about hippocampal principal cells. On the one hand, a subpopulation
of principal cells elicits network-entrained action potentials that exhibit a characteristic ectopic
waveform in vitro. On the other hand, a large number of cells feature a peculiar axon
location. We discovered a relationship between these two findings, showing that only cells
with axons originating from a dendrite were able to participate during sharp wave-ripple
oscillations.
As specific network oscillations are associated with different behavioral states, we were
interested in the modulation of network rhythms. It has been shown that enhanced levels
of oxytocin affect the formation of long-lasting spatial memory. Here, we studied the effects
of oxytocin on hippocampal network activity in vitro, showing that it selectively reduced
sharp wave-ripples, while failing to modulate gamma oscillations.
Furthermore, we investigated the neuroprotective mechanism, which is enabled by the
amyloid precursor protein. Although being strongly associated with Alzheimer's disease,
its intracellular processing provides a basis for neuroprotection. We show that the harming
impact of a hypoxic condition on hippocampal network oscillations was eased by fragments
of the amyloid precursor protein through modulation of L-type calcium channels, in vitro.
ER  -