Taylor Kaban

Topic

A Novel Cortex-Wide Hemodynamic Adaptive Change Accompanying Persistent Cortical Sensory Adaptation and its Impairment in a Mouse Model of Rett Syndrome

Department of Biology

Date & location

• Wednesday, July 29, 2026
• 10:30 A.M.
• Clearihue Building, Room A312

Examining Committee

Supervisory Committee

• Dr. Kerry Delaney, Department of Biology, University of Victoria (Co-Supervisor)
• Dr. Craig Brown, School of Medical Sciences, UVic (Co-Supervisor)
• Dr. Bob Chow, Department of Biology, UVic (Member)

External Examiner

• Dr. Kurt Smith, School of Exercise Science, Physical and Health Education, UVic

Chair of Oral Examination

• Dr. John White, Department of Mechanical Engineering, UVic

Abstract

Neural adaptation is a signature feature of the brain, and it characterizes the foundation for the fundamental form of learning that is behavioral habituation. Rett syndrome (RTT) is a neurodevelopmental disorder caused by MECP2 mutation. The MECP2 gene product plays a vital role in experience dependent plasticity. Neural adaptation is an experience dependent form of plasticity whereby repetitive stimulation of non-noxious stimuli leads to reduced neural activity in the brain. In RTT model mice our lab has shown dysfunction of cortical sensory adaptation, a form of neural adaptation. In the contralateral primary somatosensory cortex after an hour of repetitive hindlimb stimulation, neural activity to test pulses decreases by 40% compared to pre-adaptation levels in both control (WT) and RTT mice. After continuous stimulation, the cortical response to test pulses in WT mice remains persistently adapted, while RTT mice revert to pre-adaptation levels.

The brain does not process sensory information in one discrete location. It is becoming increasingly important to understand information processing in the brain from a mesoscopic point of view, making sense of processing through distributed brain circuits. It is therefore conceivable yet unknown whether the persistent cortical sensory adaptation in the primary contralateral somatosensory cortex is associated with other adaptive phenomena in distributed yet connected brain regions. It is also unknown how hemodynamics changes as a function of cortical sensory adaptation across cortical sensory processing circuits. Recent research has raised the possibility of neurovascular coupling dysfunction in Rett syndrome. Neurovascular coupling is the link between neuronal activity and cerebrovascular hemodynamics. Using red-light intrinsic optical imaging we leverage neurovascular coupling to investigate the effects of repetitive hindlimb stimulation on the resulting hemodynamics across distributed yet connected brain regions within cortical somatosensory processing circuits.

We show that after repetitive hindlimb stimulation, there are profound changes to the hemodynamic response across distributed cortical somatosensory processing regions including the ipsilateral hindlimb primary somatosensory cortex, the retrosplenial cortex, and secondary motor cortex regions. In line with the neural adaptive changes that we previously reported on in the contraHL, a widespread delayed increased reflectance develops at the end of repetitive stimulation in both WT and RTT mice. After the cessation of repetitive stimulation, the delayed increased reflectance persists in WT mice, but more quickly reverts in RTT mice, suggestive of impaired long-term neural adaptation mechanisms. In RTT mice, the onset of the earliest IOS signal change is no different to WT mice, yet the delayed increased reflectance is further delayed relative to the onset of the WT delayed increased reflectance. The difference in the late component timing but not the initial component timing is reflective of neurovascular coupling impairment. Neural adaptation after repetitive stimulation is a fundamental form of learning in the nervous system, and this research underscores the importance of improving our mechanistic understanding of neural adaptation from a cortical circuit perspective in both health and disease.