ENTORHINAL SILENCING

Elucidating the role of the entorhinal cortex through precise optogenetic and pharmacogenetic manipulations

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 Obiettivo del progetto (Objective)

'The hippocampal-entorhinal circuit is critical for the formation of new episodic memories, or memories of events that happen in a specific place and time. The discovery of cells in this circuit that respond to the animal's location in the environment suggests that these cells create a spatial context for such memories. Within this broad neural circuit, five key cell types have been described: place cells, grid cells, head direction cells, border cells, and cells that respond to a conjunction of these features. However, the mechanisms behind the generation of each firing pattern, and the function of each cell type, remain to be determined. Models have hypothesized that multi-peaked 'grid' responses are generated in layer II of the medial entorhinal cortex and converted into single-peaked 'place' responses in the hippocampus. Testing these models requires the capability to selectively manipulate individual elements of the circuit. The following experiments combine the cellular specificity of transgenic mice with novel optogenetic and pharmocogenetic tools to inactivate layer II of the medial entorhinal cortex while simultaneously recording ensembles of neurons in the entorhinal cortex or hippocampus. This genetic dissection will shed light on the basic operational principles of the circuit, and help distinguish between models of hippocampal-entorhinal interactions. Understanding the basic performance of the circuit will provide clues into how the circuit might malfunction in patients afflicted with Alzheimer's disease or epilepsy.'

Introduzione (Teaser)

Growing knowledge about how different regions of the brain interact is providing insight into how memories are stored. An EU-funded project added to our understanding.

Descrizione progetto (Article)

The entorhinal cortex and hippocampus are areas of the brain involved with forming and storing episodic memories. These include both memories of discrete events as well as information about where and when they occurred. The activities of these two areas are thought to provide a map of the environment suitable for spatial navigation. This map also provides a place where non-spatial elements can be overlaid. Yet, how these cells interact remains an open question.

To address this issue, the project ENTORHINAL SILENCING relied on transgenic technologies to isolate cells in the medial entorhinal cortex (MECII). From there, researchers hoped to determine which functional cell types in the MECII signal to the hippocampus, and what happens when those cells are silenced.

During the first part of the study, researchers discovered that cells in the MECII project to the dentate gyrus and the CA3 region of the hippocampus. This finding suggests that these cells may also play a role in the firing of cells that identify 'place'.

Prior to this study, four cell types in the MECII had already been identified: border cells, head direction cells, grid cells and conjunctive cells that give directional information. Researchers then set out to determine which are involved in communication with the hippocampus. To do so, they silenced the MECII cells in mice as they were navigating a box. Because only transgenic neurons can be silenced, it is possible to identify those key cells. The experiment showed that the neurons involved are border and grid cells.

These results deepen our understanding of how cells are connected and interact to form and maintain episodic and spatial memories. Further research will continue to explore the relationships between different parts of the brain.