Evaluierung der Beteiligung von 'grid cells' an Pfadintegration und räumlichem Lernen
Zusammenfassung der Projektergebnisse
The mammalian hippocampal-entorhinal system is thought to be responsible for the encoding of internal representations of space. Since the discovery of grid cells in the medial entorhinal cortex (MEC), neurophysiological data and computational models have suggested that these neurons serve path integration (PI), a highly conserved, self-motion-based navigation strategy. However, more direct empirical evidence supporting this hypothesis has been missing due to a lack of selective manipulations of grid cell activity and adequate behavioural assays. During the first funding period, we overcame these limitations and directly tested this hypothesis. We first achieved selective disruption of grid cell activity by removing N-methyl-D-aspartate glutamate receptors (NMDARs) from the retrohippocampal (RH) region. Notably, the genetic manipulation did not affect the activity of other spatially selective cells in the MEC and the hippocampus. We then used these mice with disrupted grid cell activity to test the hypothesis that grid cells support PI. We found that mice with disrupted grid cell activity exhibit impaired PI performance in the L-maze. Moreover, by using the same mice for in vivo electrophysiological recordings and behavioural tests, we were able to correlate the degree of the NMDARs ablation with the degree of altered grid cell activity and the degree of PI impairment. Our study demonstrates that NMDAR ablation in the RH region disrupts grid cell firing and PI performance, providing strong experimental support for the hypothesis that grid cell activity underlies PI navigation. During the second funding period, we studied the role of the MEC in different behavioural paradigms involving location and object learning. Our approach was straightforward, we inactivated the MEC using chemogenetics while mice performed different behavioural tasks. During exploration tasks, we confirmed the involvement of the MEC in object displacement detection and also found that it is involved in object recognition in a simple setting where only 2 objects -and not 4 - have to be discriminated. Moreover, MEC-inactivation delays image discrimination and impairs the formation and/or retrieval of long-term memories in an operant box setting. These results indicate that in addition to its wellstudied function in spatial learning and navigation, the MEC is also involved in learning and memory of nonspatial cues.
Projektbezogene Publikationen (Auswahl)
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(2018) Impaired path integration in mice with disrupted grid cell firing. Nature Neuroscience 21:81-91
Gil M, Ancau M, Schlesiger MI, Neitz A, Allen K, De Marco RJ, Monyer H
