Electroanatomy of hippocampal networks: Topographic distribution of co-active cells and its plasticity

• Applicants: Privatdozent Dr. Martin Both; Professor Dr. Andreas Draguhn
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 351649465

• Final Report Year: 2023

Final Report Abstract

Local neuronal networks express highly coordinated spatiotemporal activity patterns, which include the activation of functional neuronal ensembles. During a given behavioral-cognitive situation, these patterns are expressed in multiple local networks, either simultaneously or in sequences generated by propagating network activity. In the project, we studied an important model system for coherent network activity, the rodent hippocampus. Our leading questions were how these patterns are generated, how they propagate and what are their differential properties in different sub-networks of the system. We used different electrophysiological methods to monitor and manipulate network activity in mouse brain slices, including microelectrode arrays which can register network activity (socalled local field potentials) from multiple spots, thereby providing data with high spatial and temporal resolution. We also made recordings at the cellular level to study specific questions about the mechanisms determining participation of single neurons in the global network patterns. Our main result at the cellular level is that the activity of the axon (the ‘output’ fiber of neurons) and the dendrites (the system collecting synaptic inputs) interact in a hitherto unknown way, such that synaptic inputs modulate the probability of a specific form of output signals, so-called antidromic action potentials (AP). At the network level, we were able to define the conditions for triggering two different patterns of network activity in a systematic way. These patterns, called γ-oscillations or sharp-wave ripple complexes (SPW-R), occur in different cognitive-behavioral situations. Using modern light-based stimulation tools (‘optogenetics’) we could show that the kinetics of activation decides which of the two patterns occurs. Our findings from the in vitro-preparation of hippocampal slices sets important boundary conditions for understanding the generation of the respective patterns in vivo. Finally, in cooperation with our Mexican partners we employed a super-high resolution electrode array to map the generation and propagation of a specific pathological pattern of network activity, called ‘fast ripples’ (FR). These events are regarded a marker for chronic epileptic syndromes. We found that fast ripples can be generated near-synchronously in various regions of the slice preparation, without apparent crosstalk between the spots of FR generation. Furthermore, propagation of FR did not exclusively follow established pathways but could also invade regions which are, under normal conditions, located upstream the hippocampal networks. This reverse propagation may constitute a mechanism for the spread of pathological network activity and should be analyzed in animal models in vivo.

Publications

• Early Appearance and Spread of Fast Ripples in the Hippocampus in a Model of Cortical Traumatic Brain Injury. The Journal of Neuroscience, 38(42), 9034-9046.
  Ortiz, Franco; Zapfe, W.P. Karel; Draguhn, Andreas & Gutiérrez, Rafael
  
• Electrical coupling between hippocampal neurons: contrasting roles of principal cell gap junctions and interneuron gap junctions. Cell and Tissue Research, 373(3), 671-691.
  Traub, Roger D.; Whittington, Miles A.; Gutiérrez, Rafael & Draguhn, Andreas
  
• Synaptic entrainment of ectopic action potential generation in hippocampal pyramidal neurons. The Journal of Physiology, 596(21), 5237-5249.
  Thome, Christian; Roth, Fabian C.; Obermayer, Joshua; Yanez, Antonio; Draguhn, Andreas & Egorov, Alexei V.
  
• Synchronicity of excitatory inputs drives hippocampal networks to distinct oscillatory patterns. Hippocampus, 30(10), 1044-1057.
  Geschwill, Pascal; Kaiser, Martin E.; Grube, Paul; Lehmann, Nadja; Thome, Christian; Draguhn, Andreas; Hollnagel, Jan‐Oliver & Both, Martin
  
• Enriched Environment Modulates Sharp Wave-Ripple (SPW-R) Activity in Hippocampal Slices. Frontiers in Neural Circuits, 15.
  Landeck, Lucie; Kaiser, Martin E.; Hefter, Dimitri; Draguhn, Andreas & Both, Martin