Doctoral Defense in Life and Medical Sciences – Sana Gadiwalla

On Monday, June 8, Sana Gadiwalla will defend her doctoral dissertation in Life and Medical Sciences at the Faculty of Medicine of University of Iceland. The dissertation is titled: Genetic and activity-dependent regulation of intrinsic excitability in olfactory bulb projection neurons.

The opponents are Dr. Venkatesh N. Murthy, professor at Harvard University, and Dr. Jamie Johnston, associate professor at University of Leeds.

The academic supervisor was Pétur Henry Petersen, and the advisor was Elisa Galliano. In addition, the doctoral committee included Eiríkur Steingrímsson, Ragnhildur Þóra Káradóttir, and Þór Eysteinsson, all professors.

Stefán Þórarinn Sigurðsson, professor, ViseDean of the Faculty of Medicine, will preside over the ceremony, which will take place in the Ceremonial Hall of the University of Iceland and begins at 1:00 PM.

Abstract

Neurons must precisely regulate their intrinsic excitability to maintain stable circuit function while preserving the capacity for plasticity, yet the transcriptional mechanisms underlying this regulation in specific neuronal populations remain largely unknown. The microphthalmia-associated transcription factor (MITF) is expressed in olfactory bulb (OB) projection neurons (mitral and tufted cells), and while previous work has implicated it in modulating intrinsic properties in vitro, its ex vivo function is poorly understood. This thesis examines how Mitf regulates neuronal excitability in OB projection neurons and how its loss disrupts circuit plasticity.
Using whole-cell patch clamp electrophysiology, we first established that wild-type projection neurons exist along a heterogeneous continuum of electrophysiological properties rather than forming discrete subtypes. We then used two complementary mouse models, Mitfvga9(complete loss of function) and MitfK243R (a hypomorphic mutation preventing acetylation at a conserved lysine residue), to characterize projection neuron electrophysiology and transcriptional responses under basal conditions and following short-term odor exposure. Mitf mutants exhibited altered intrinsic excitability and impaired temporal coding dynamics alongside significantly increased inhibitory currents, indicating both cell-autonomous and circuit-wide effects. Bulk RNA-sequencing of Mitfvga9 OB tissue revealed broad transcriptional dysregulation across 21 neuronal pathways related to synaptic function, ion channel regulation, and excitability. The similar physiological phenotype of MitfK243R mutants further implicates activity-dependent acetylation as a key regulatory mechanism.
Following odor exposure, wild-type mitral cells showed electrophysiological and transcriptional changes consistent with homeostatic plasticity, including robust activity-dependent gene expression across 696 genes, while Mitf mutants failed to mount equivalent adaptive responses. Together, these findings identify MITF as a regulator of both basal neuronal properties and experience-dependent transcriptional plasticity and suggests that post-translational modification of transcription factors can serve as a molecular interface between sensory activity and lasting changes in circuit function.

About the Doctoral Candidate

Sana Gadiwalla was born in 1993 in Seattle, Washington, USA. She completed a Bachelor of Science degree in Biology from the University of Washington in 2015. After completing her undergraduate studies, she worked as a laboratory manager at Pennsylvania State University.

In 2020, she completed a joint Master of Science degree in Science, Technology, and Health with a specialization in Life Sciences from the University of Strasbourg and the University of Freiburg. Her master’s thesis research was conducted at the Department of Physiology, Development and Neuroscience at University of Cambridge.

In 2021, Sana began her doctoral studies at the University of Iceland and carried out part of her research at University of Cambridge before completing her PhD.