A05

Identified neuronal ensembles subserving spatial coding in the medial entorhinal cortex

click for full picture
Local and distant input control medial entorhinal cortex excitation.

The activity of spatially-tuned excitatory neurons in the hippocampal-entorhinal formation – i.e. place cells in the hippocampus and grid cells in the medial entorhinal cortex (mEC) – is a prerequisite for the generation of spatial maps. The mechanisms underlying the generation of spatial representations are not known, but are likely to depend on the interaction between excitatory and inhibitory neurons within local microcircuits in the hippocampus and mEC, as well as the interaction between these two brain regions.

Here we propose to employ tracing studies and in vitro electrophysiological investigations to characterize the connectivity between modularly structured neuronal ensembles in the mEC. Furthermore, we will perform photostimulation-assisted neuronal excitation and inhibition in freely moving mice to study the role of defined excitatory neurons in microcircuits of the mEC and their contribution to the generation of local grid cells and hippocampal place cells.

The scheme shows the hippocampus in grey with the firing field of a place cell, and the medial entorhinal cortex in green with modularly organized structures comprising grid cells and interneurons. Examples of firing fields and peristimulatiom histograms for the two cell types are shown in the magnified module on the right, and representative action potential firing for an interneuron and an excitatory cell to the right of the module below. Question marks denote putative connections that will be characterized in vitro and in vivo.
Publications
Allen K*, Gil M, Resnik E, Toader O, Seeburg P, Monyer H (2014) Impaired path integration and grid cell spatial periodicity in mice lacking GluA1-containing AMPA receptors. J Neurosci, in press.

Buetfering C, Allen K*, Monyer H (2014) Parvalbumin-expressing interneurons provide grid cell- driven recurrent inhibition in the medial entorhinal cortex Nature Neuroscience, in press.

Melzer S, Michael M, Caputi A, Eliava M, Fuchs EC, Whittington M., Monyer H (2012) Long-range projecting GABAergic neurons modulate inhibition in hippocampus and entorhinal cortex, Science 335: 1506-1510.

Caputi A, Fuchs EC, Allen K*, LeMagueresse C, Monyer H (2012) Selective reduction of AMPA currents onto hippocampal interneurons impairs network oscillatory activity. PLoS One 7(6):e37318.

Allen K*, Fuchs EC, Jaschonek H, Bannerman DM, Monyer H (2011) Gap junctions between in- terneurons are required for normal spatial coding in the hippocampus and short-term spatial memory. J. Neurosci 31:6542-6552.

Korotkova T, Fuchs EC, Ponomarenko A, von Engelhardt J*, Monyer H (2010) NMDA receptor ablation on parvalbumin-positive interneurons impairs hippocampal synchrony, spatial rep- resentations, and working memory. Neuron 68:557-569.

von Engelhardt J*, Doganci B, Jensen V, Hvalby O, Göngrich C, Taylor A, Barkus C, Sanderson DJ, Rawlins JNP, Seeburg PH, Bannerman DM, Monyer H (2008) Contribution of hippocampal and extra-hippocampal NR2B-containing NMDA receptors to performance on spatial learn- ing tasks. Neuron 60:846-860.

Fuchs EC, Zivkovic AR, Cunningham MO, Middleton S, LeBeau FE, Bannerman DM, Rozov A, Whit- tington MA, Traub RD, Rawlins JN, Monyer H (2007): Recruitment of parvalbumin-positive interneurons determines hippocampal function and associated behavior. Neuron 53:591-604.

*Principal investigators of other projects within the CRC