Date of Completion

2018

Document Type

Honors College Thesis

Department

Neuroscience

Type of Thesis

Honors College, College of Arts and Science Honors

First Advisor

Jeremy Barry

Second Advisor

Sayamwong Hammack

Third Advisor

Matthew Weston

Keywords

Pten, Autism, CA1, Place Cells, in vivo

Abstract

While cognitive deficits have been described in the heterozygous Pten (+/-) KO mouse model of autism, little work has been done to demonstrate how corresponding in vitro physiological alterations in this model may underpin these cognitive deficits in vivo. As Pten KO (+/-) is known to alter electrophysiological characteristics of neurons in vitro, this study measures the in vivo electrophysiological characteristics of CA1 interneurons, pyramidal cells, and place cells which may underlie the spatial cognitive deficits seen in the model. Four transgenic conditional heterozygous Pten+/loxPloxP;Gfap-cre mice (HetPten) and four homozygous Pten littermate control mice were used in this study. This transgene drives cre expression and excision of the Pten gene in hippocampal granule cells of the dentate gyrus, and neurons in CA2 and CA1, but not astrocytes. In vivo local field potentials and single cell recordings were made in CA1 of each mouse during an open field foraging task in two distinct arenas. HetPten mice were found to have increased interneuron and pyramidal cell firing rates. In addition, place cells demonstrated abnormal properties including increased out-of-field firing rates, an increased number of fields, and trends towards larger field sizes that were less stable in comparison to controls. HetPten mice had slower CA1 fast gamma oscillations and more variable speed/theta oscillation correlations. Behaviorally, there were weak trends towards decreased motor output compared to controls. These data suggest that the electrophysiological alterations due to Pten KO (+/-) in mouse hippocampal neurons lead to hyperactivation of CA1 interneurons, pyramidal cells, and place cells.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Available for download on Wednesday, April 17, 2019

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