Neuronal morphology and plasticity in the Scn1b mouse model of Dravet syndrome

dc.contributor.advisorHoward, MacKenzie
dc.creatorAhmed, Alisha
dc.date.accessioned2023-07-31T15:01:07Z
dc.date.available2023-07-31T15:01:07Z
dc.date.issued2021
dc.description.abstractIn order to selectively process their inputs and make outputs to other neurons, a neuron’s physiology is tightly regulated by a variety of factors, including morphology and synaptic plasticity. The morphology, or structure, of a neuron can determine its intrinsic properties. Synaptic plasticity determines a neuron’s ability to strengthen and weaken in response to inputs, influencing its effects in learning and memory. When any of these processes are impaired, it can cause severe neuronal dysfunction and broader cognitive deficits, leading to neurological disease. Our lab is interested in Dravet syndrome (DS), which is a severe genetic epilepsy that leads to prolonged seizures, developmental delays, and severe cognitive deficits. Mutations in the SCN1B gene, which encodes the protein β1, have been linked to DS. We use an Scn1b knockout mouse model, which models many aspects of DS including spontaneous seizures and early death, to study the neurophysiological changes underlying the disease. β1 is important in regulating neuronal excitability and physiology, and has also been shown to play a role in neuron growth and development. We have found that loss of β1 leads to abnormal intrinsic and synaptic physiology in one of the primary neuron types responsible for learning and memory: hippocampal pyramidal neurons. My research aims to examine how loss of β1 affects both neuronal morphology and synaptic plasticity, the selective strengthening (long-term potentiation) or weakening (long-term depression) of neuronal synapses, in hippocampal pyramidal neurons. Our lab has found that hippocampal pyramidal neurons are hyperexcitable, motivating me to hypothesize that dendritic arborization and spine density would be altered in Scn1b knockouts, because neuronal structure is tightly linked to neuronal physiology as it largely affects intrinsic properties of neurons. Our lab has additionally found that long-term potentiation is lost in Scn1b knockouts. This finding suggests that these knockout neurons may have reached an upper limit of plasticity, leading me to hypothesize that long-term depression is increased in Scn1b knockout mice. To examine neuronal morphology, I analyzed dendritic branching patterns and spine density in Scn1b knockout neurons, and found no overall changes in morphology. To examine long-term depression, I analyzed local field potential recordings using a low-frequency stimulus, and found no difference in long-term depression between knockouts and wildtype littermates. My findings illustrate that the links between neuronal physiology, morphology, and plasticity are altered atypically in β1-deficient hippocampal neurons, suggesting a complex role for β1 in this brain region.en_US
dc.description.departmentNeuroscienceen_US
dc.identifier.urihttps://hdl.handle.net/2152/120709
dc.identifier.urihttp://dx.doi.org/10.26153/tsw/47544
dc.language.isoengen_US
dc.relation.ispartofHonors Thesesen_US
dc.rights.restrictionOpenen_US
dc.subjectneuroanatomyen_US
dc.subjectsynaptic plasticityen_US
dc.subjectpyramidal neuronen_US
dc.subjecthippocampusen_US
dc.subjectdendritesen_US
dc.subjectspinesen_US
dc.subjectCA1en_US
dc.subjectDravet syndromeen_US
dc.subjectbeta 1en_US
dc.subjectscn1ben_US
dc.titleNeuronal morphology and plasticity in the Scn1b mouse model of Dravet syndromeen_US
dc.typeThesisen_US
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