Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746772
Title: Self-motion, environmental, and cholinergic influences on grid cell firing
Author: Carpenter, Francis
ISNI:       0000 0004 7226 032X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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Abstract:
As an animal navigates an environment, grid cells emit action potentials at the vertices of a tessellating triangular pattern. The distance between adjacent vertices varies between subsets of grid cells, with each subset forming a functional ‘module’. Combined, this periodic firing and modular organisation is theoretically an extremely efficient means of encoding an animal’s location within its environment, and may support goal-directed navigation in enabling the calculation of vectors connecting pairs of locations. The mechanisms by which grid cell firing patterns are generated and their functional contributions to cognition remain obscure however. In this thesis, I present the results of a number of experiments which shed light on these issues. In the first experiment, I recorded from grid cells in rats exploring an environment containing two perceptually identical compartments connected by a corridor. This environment was designed to place the putative self-location and sensory inputs to grid cells in conflict, allowing inference of the relative contribution of each to the generation of grid cell firing patterns. During early exposures to the environment, firing patterns were replicated between the two compartments, demonstrating the significance of the identical sensory cues. However, firing patterns came to distinguish the compartments following prolonged exposure to the environment. Indeed, a single continuous pattern spanning both compartments eventually formed, indicating that self-motion cues gradually come to dominate sensory cues. Current models of navigation employing grid cells require regular and coherent firing patterns, and these results thus provide the first evidence that grid cells are capable of subserving such functions in complex environments. Recent results suggest that the medial septum supports grid cell function through the encoding of one or more speed signals. Its exact contribution, and the roles of its constituent neuronal subtypes, remain undetermined however. In the second experiment, I therefore recorded from grid cells in mice while manipulating the activity of medial septal cholinergic neurones using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Increasing septal cholinergic tone reduced the frequency of theta oscillations by shifting the theta frequency vs running speed relationship to lower frequencies, without affecting its depth of modulation. However, no change was observed in grid firing patterns in either familiar or novel environments, consistent with a lack of change in the putative speed signals used by grid cells. An absence of novelty-induced expansion of grid scale prevented testing of the theory that, in rats, this phenomenon depends on increases in cholinergic tone. However, increasing the excitability of medial septal cholinergic neurones led to a pattern of 6 behaviour normally seen on exposure to novel environments. That is, the effects on behaviour of increasing cholinergic tone were consistent with a role for acetylcholine in the signalling of novelty. Finally, I present preliminary work in which recordings of grid cells from wild type mice demonstrate that the room in which a grid cell is recorded can affect the scale, temporal stability, and regularity of its firing pattern. As the local environment between the rooms was consistent, such differences likely indicate a role for distal sensory cues in anchoring and stabilising grid cell firing patterns.
Supervisor: Barry, C. ; Burgess, N. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.746772  DOI: Not available
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