Determining the impact of neocortex size changes on information processing : implications for neurodevelopmental disorders

Student thesis: Doctoral Thesis

Abstract

Development of the cerebral cortex is highly regulated by genetically programmed sequential events. Alterations in this process by genetic or non-genetic factors can lead to over- or underproduction of cortical neurons and abnormal connectivity, resulting in neurodevelopmental disorders, such as autism spectrum disorder (ASD). Although ASD patients often exhibit atypical sensory processing, the relationship between abnormal cortical size and sensory processing is still unclear. Here we hypothesise that abnormal cortical expansion during development leads to atypical sensory processing. To test this hypothesis, we utilized a recently established mouse model, in which the number of superficial cortical excitatory neurons is increased pharmacologically during embryonic development. This mouse model is also known to exhibit macrocephaly and autism-like phenotypes. In this project, we assessed their auditory perception behaviourally and evaluated neuronal population activity in the auditory cortex and medial geniculate nucleus through high-density in vivo electrophysiological recording. Our results indicate that the overproduction of superficial cortical excitatory neurons negatively affects auditory processing. Treated mice exhibited hyposensitivity to near-threshold auditory stimuli during behavioural auditory detection assessment. Further, their cortical neurons showed lower spontaneous and auditory evoked activity as well as delayed peak response latency. We also observed atypical cortical functional connectivity. Overall, our study suggests that abnormal cortical expansion during development results in atypical auditory processing, and provides further insights into the neural basis of perceptual deficits in neurodevelopmental disorders such as ASD.
Date of Award26 May 2021
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorShuzo Sakata (Supervisor) & Trevor Bushell (Supervisor)

Cite this

'