Back to search

FRIMEDBIO-Fri prosj.st. med.,helse,biol

Transformation of grid signals to place signals in the mammalian space circuit

Awarded: NOK 3.0 mill.

The mammalian space circuit is known to contain several functionally specialized cell types, such as place cells in the hippocampus and grid cells, head direction cells and border cells in the entorhinal cortex, but the interaction between them is poorly understood. We are currently using a combined optogenetic-electrophysiological strategy to determine the functional identity of entorhinal cells with monosynaptic projections to the place-cell population in the hippocampus. Microbial opsins have been expressed selectively in the hippocampus-targeting subset of entorhinal projection neurons by injecting retrogradely transportable opsin-coding recombinant adeno-associated viruses in the hippocampus. We have been able to identify virally transduced cells in medial entorhinal cortex as cells that fire at fixed minimal latencies in response to local flashes of light. The majority of responsive cells turn out to be grid cells but short-latency firing can also be induced in border cells and head-direction cells, as well as spatial cells with more irregular firing fields, suggesting that place cells are generated by convergence of signals from a broad spectrum of entorhinal functional cell types. These signals are consistent with data that we have collected in juvenile rats, where we find border cells on the first day of outbound exploration, whereas grid cells need a few more days to mature. A limitation of the published results is that they provide only the average input to the place-cell population. To determine the inputs to individual place cells, and to assess how these inputs shape the properties of place cells, we are currently developing a virus-based method that will enable us to target a single cell in CA3 with a pseudotyped and G-protein deleted rabies virus expressing GcAMP6. Subsequent rabies infusion is expected to selectively label cells with input to the target cell. Using endoscopy, we will perform in vivo calcium imaging of monotranssynaptically labeled neurons in MEC layer II.

Place cells are hippocampal neurons that fire if an animal moves through a particular location in space. These cells are embedded in a larger (para)hippocampal brain circuit for dynamic representation of self-position. A key element of this wider circuit is the entorhinal grid cell, which fires only when the animal moves through locations that collectively define a periodic triangular array across the environment. Grid cells co-exist with other cell types encoding head direction, geometric borders, or con junctions of features. The network of entorhinal cell types is thought to form an essential part of the brain?s coordinate system for metric navigation but the mechanisms generating each firing pattern, and the function of each cell type, remain to be det ermined. Technology for large-scale neuronal ensemble recording has made it possible to address these unsolved questions by monitoring population dynamics during spatial navigation. However, insights are still hampered by a lack of tools for selective int ervention. Such tools are now becoming available. New optogenetic technologies allow target cell types to be depolarized or hyperpolarized selectively in even the most entangled brain circuits. We shall employ these techniques to investigate how spatial l ocation is computed in the entorhinal-hippocampal system. Specifically, we shall establish (i) which entorhinal cell types (grid cells, head direction cells, border cells) project into the place-representing regions of the hippocampus, (ii) which cell typ es project to an individual hippocampal place cell, and (iii) how the particular combination of functional inputs shapes the properties of the place cell. The morphological identify of the incoming projections will also be identified. Taken together, thes e expeirments will pioneer the functional analysis of neural circuits and may, perhaps for the first time, provide us with mechanistic insight into a non-sensory neural code transformation in the mammalian cortex.

Publications from Cristin

No publications found

No publications found

No publications found

No publications found

Funding scheme:

FRIMEDBIO-Fri prosj.st. med.,helse,biol

Funding Sources