Vector coding in the entorhinal cortex

Naturen er full av levende organismer og objekter som står stille eller beveger seg. I dette prosjektet ønsker vi å forstå hvordan hjernen koder for slike objekter ved å registrere aktivitet fra nerveceller i entorhinal cortex i mus eller rotter som beveger seg fritt i miljøer som inneholder objekter. Mediale entorhinal cortex (MEC) er involvert i stedsansen, og mange MEC-celler er spesialiserte for spatial navigering. Den mest kjente typen celle vi fant er gittercellen. Disse cellene er foreslått å fungere som et koordinatsystem som brer seg utover enhver flate på en slik måte at aktivitetsfeltene er distribuert med lik avstand mellom hvert felt, i et repeterende heksagonalt mønster. Det er foreslått at gittercellene fungerer som todimensjonale målestaver. Andre spatielle celler i MEC informerer om hoderetningen til subjektet, grensene for miljøet og farten til subjektet. Nylig oppdaget vi en ny type celle som signaliserer både avstand og retning fra subjektet til et objekt. Siden aktiviteten til disse cellene kan beskrives som en vektorrelasjon, kalte vi disse cellene objektvektorceller (OV-celler). I denne søknaden er vi interesserte i å finne ut om det er spesielle egenskaper ved objekter som utløser objektvektor-responser, eller om OV-cellene er uaffisert av forskjeller i kvalitet og utseende av objektet. I fortsettelsen av dette ønsker vi å finne ut om OV-responsen er avhengig av motivasjonsnivå. Vi ønsker også å forstå hvilke faktorer som generer slik vektoraktivitet. Er OV-responsen for eksempel avhengig av registrering av selvbevegelse? Er OV-cellene samlokaliserte eller klustret? Alt i alt ønsker vi å beskrive og forstå vektorkoding av posisjon i hjernen, å finne ut hvordan denne responsen blir generert og å sammenligne med andre spatiale kodingssystemer.

The project has led to the following overall outcomes and impacts: - The project has identified which factors in the environment that OV cells use to anchor firing to given positions. - It has shown that cells in the hippocampus encode information about objects and that this primarily happens on the level of neuronal populations. - It has shown that OV cells are excitatory stellate or pyramidal cells in MEC and parasubiculum and that their anatomical location is different from that of grid cells. - It provides sufficient knowledge about OV cells to construct models of their formation and operation as well as their interactions with other functional cell types of the circuit. - It provides the breadth of data needed to construct new computational models for vectorial coding in MEC. - It is one of the first projects to use portable 2-photon microscopes to determine spatial coding mechanisms in widespread anatomical circuits. - It is one of the first projects to use Neuropixels silicon probes to record from hundreds of cells in MEC and hippocampus. The findings have inspired the design of studies searching for possible early functional markers of Alzheimer’s disease in human subjects, in collaboration with the K.G. Jebsen Centre for Alzheimer’s Disease. The first symptoms of Alzheimer's disease are often reduced sense of space and episodic memory, functions that are strongly dependent on the hippocampal formation and entorhinal cortex. Research at the Kavli Institute for Systems Neuroscience indicates that Alzheimer’s disease may start by slow degeneration of neural circuits for space and time. By identifying variables that control firing in OV cells, we prepare the ground for paradigms to distinguish modes of spatial mapping in humans in neuropsychological tests and functional MRI.

Much of what we know about high-level cortical neural coding has been obtained in the spatial mapping system of the entorhinal cortex. Until recently, this brain region was a blank spot on the brain’s functional map but today we know that it contains a number of computationally specialized cell types with dedicated roles in mapping of the local spatial environment: grid cells, head direction cells, border cells, and speed cells. Insights have been limited, however, by an almost exclusive reliance on recordings from rodents foraging in empty enclosures that are quite different from the richly populated, geometrically irregular environments of the natural world. We have recently tested mice in more complex environments - environments that contain discrete objects and so are different from the empty and open environments used to detect previous cell types. The tests showed that medial entorhinal cortex contains an abundant number of cells that use a vectorial code to represent location. These newly discovered cells - named object vector cells - fire at specific locations determined by distance and direction from discrete objects in the environment. Their combined firing can be used to infer location. In the present proposal, I wish to establish how vector coding enables spatial representation in the entorhinal-hippocampal spatial mapping system. We shall (i) identify the factors that cause object vector cells to fire to some objects and not to others, (ii) determine the sources of their metrics, and (iii) establish the morphological nature of object vector cells, their distribution in the network, and the relationship between object vector cells and cells with similar properties in other parts of the hippocampal-entorhinal system. Obtaining answers to these questions will significantly add to our understanding of the function of object vector cells in coding of space and their interaction with other elements of the space circuit.