Disorganized phase coding in the hippocampus and lateral septum in a maternal immune activation model of schizophrenia risk

Author: Speers, Lucinda Jean

Date: 2021

Publisher: University of Otago

Type: Thesis

Link to this item using this URL: http://hdl.handle.net/10523/12481


Episodic memory requires information to be stored and recalled in sequential order, and current evidence suggest that these processes are disrupted in schizophrenia. Hippocampal phase precession and theta sequences are thought to provide a biological mechanism for the sequential ordering of experience at timescales suitable for plasticity, suggesting that they could provide the neural scaffolding for episodic memory processes. However, neither phase precession nor theta sequences have previously been examined in any models of schizophrenia risk. The principal aim of experiment 1 was to investigate phase precession and theta sequences in a maternal immune activation (MIA) rodent model. Following implantation of tetrodes into the dorsal CA1 region of the hippocampus, both single unit and local field potential (LFP) recordings were obtained as animals ran around a rectangular track for a food reward. Results showed that, while individual pyramidal cells located in the CA1 region continued to precess normally in the MIA group, the starting phase of precession as an animal enters a new place field was considerably more variable in MIA animals when compared to controls. A critical theoretical consequence of this variability is that the ordered representation of experience, encoded via theta sequences, should become disorganized. In support of this theory, theta sequences were disrupted in the MIA group. Disorganized theta sequences could potentially interfere with the transformation of the spatial phase code to downstream regions that are thought to be important for the integration of contextual and reward information, such as the lateral septum (LS). In experiment 2, the same protocol was followed as in experiment 1, except that tetrodes were implanted into the rostral LS. Results from experiment 2 indicated that, although spatially selective rate coding was rare, robust phase precession relative to the hippocampal theta rhythm was observed across a substantial proportion of LS cells irrespective of intervention group. However, in contrast to the shallow precession slopes observed for cells in the control (CTL) group, the range of phase precession, as measured by the slope of the circular-linear correlation of phase and position, was frequently in excess of a single theta cycle for the MIA group. This was a novel finding, as phase precession in excess of 360⁰ has generally not been observed in previous studies. A partially overlapping subset of cells in the LS also demonstrated bidirectional speed-modulated properties, consistent with the theoretical proposal that the LS may be functionally important for the integration of spatial and goal-related locomotor responses. These results provide the first evidence of disturbed phase coding in an animal model of schizophrenia risk that, if it occurs in schizophrenia, may explain some aspects of the cognitive symptoms associated with the disorder, including disorganized sequential processing and an abnormal discretization of spatial and contextual information.

Subjects: phase precession, theta sequences, hippocampus, lateral septum, schizophrenia", maternal immune activation, spatial memory

Citation: ["Speers, L. J. (2021). Disorganized phase coding in the hippocampus and lateral septum in a maternal immune activation model of schizophrenia risk (Thesis, Doctor of Philosophy). University of Otago. Retrieved from http://hdl.handle.net/10523/12481"]

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