M.Sc Thesis

M.Sc StudentIsmakov Revekka
SubjectStability and variability of spatially- modulated
neuronal firing patterns
DepartmentDepartment of Medicine
Supervisor ASSOCIATE PROF. Dori Derdikman
Full Thesis textFull thesis text - English Version


The spatially-modulated neurons within the hippocampal formation of the brain are believed to be a mechanism by which memory is consolidated and physical space is perceived. These neurons include place cells, which are pyramidal neurons in the hippocampus that fire whenever the animal transverses a given location of an arena; and grid cells, located in the entorhinal cortex, which fire in a specific pattern spanning the entire environment whose firing fields form a periodic, equal-distanced hexagonal array. These neurons have been shown to play a significant role in spatial navigation and in the perception of self-location. Beyond purely mapping out space, these neurons have also been suggested to be involved in the formation and consolidation of memory.

The firing properties of these cells tend to be stable and reliable when the animal is in the same environment, exhibiting neuronal activity when the animal traverses inside the firing fields, and remaining virtually silent when outside of them. As a means by which to signify change, the neurons change the location of their firing fields when placed in a different environment. This phenomenon is known as "remapping."

In this research, we investigate how robust, reliable, and stable the firing fields of these neurons tend to be. We examined this through two different methods: a chemogenetic approach using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) to silence hippocampal cells, and a computational method, analyzing firing activity patterns of individual grid cell fields. 

DREADDs is an engineered G protein-coupled receptor that responds exclusively to synthetic small molecules. We used an inhibitory type of DREADD to inactivate hippocampal place cells and observe the effects on the firing fields after recovery. Specifically, we wanted to see whether the fields returned to the same location or rather, remapped. Results found that both cases occur, with fields sometimes remapping and other times reverting to the same place.

In the second part of the research, we examined the firing patterns of a set of grid cells. We found that the activity between firing fields of individual grid cells exhibited a larger variability than would have been expected by shuffle measures. Further analysis revealed that this overdispersion is mainly the result of one specific strongly-firing grid field. Tending to be located near the borders of the environment, this field hints at the possibility that it may act as an anchoring point, or pivot point, for the formation of the grid cell orientation and phase.

These findings expose that the firing fields of both place cells and grid cells are not as static as previously assumed. The firing patterns of place cells do not remain the same when neuronal activity is manipulated through pharmacological means, grid cells do not exhibit uniform firing rates among the fields, and both suggest that other information is being relied aside from purely spatial that results in this instability and non-uniformity.