Transgenic activation of the same entorhinal inputs leads to the same hippocampal network response Jasmine Dickinson Kentros lab May 2012

Memory and the Hippocampus Patient HM, 1953

Hippocampus Circuitry and the DREADD Mice Inject CNO  Binds to special receptors in MEC  Increases firing in MEC Clozapine-n-oxide (CNO) only binds to the transgenic receptors. CNO is a tool to activate the receptors.

Place cells and grid cells Grid cells (Medial Entorhinal Cortex) Place cells (hippocampus) Grid cells code for general space Place cells code for specific places How do grid cells in the medial entorhinal cortex transfer their information to place cells in the hippocampus?

Activating Layer 2 Induces Changes in CA1 Firing Expand field Note: Fields return to baseline after CNO wears off Remap to new location Turn off Turn on

Same cells, different days – normal place cells Baseline (30 min) CNO (2 hours) Day 1 Day 2 Place field doesn’t change during the CNO session Same cell fires in the same place

Same cells, different days – transgenic animals Expands field Remaps to new location The cells remap, but they do the same thing both days Turns on/ increases firing Turns off

Correlation scores CNO period broken down into four 30-min pieces Both groups have well correlated fields during CNO across days, even though the +/+ group remaps

What does this mean? For transgenic animals, there is an initial remapping between BL and CNO, but once the cells remaps, they stays that way. This remapping is statistically indistinguishable from the lack of changes seen in stable recordings from control animals across multiple CNO injections suggesting stable remapping. This argues for “hard wired” connections between MEC input and CA1. “Artificial remapping” is preserved across several synapses (DG, CA3).

Thanks to: Cliff Kentros Aldis Weible Dave Rowland Everyone else in the Kentros Lab SPUR