Translational Regulation in Excitatory Neurons Controls Stress Reactivity and the Antidepressant Response to Ketamine

Major depressive disorder (MDD) is a leading cause of disability worldwide, with nearly one-third remaining treatment-resistant. Chronic stress is a major risk factor for MDD, whereas acute stress is adaptive and mediated by hypothalamic-pituitary-adrenal axis activation. Ketamine produces rapid antidepressant effects, partly through mammalian target of rapamycin complex 1 (mTORC1) signalling, which phosphorylates 4E-Binding Protein 1 and 2 (4E-BPs) to promote synaptic plasticity. This thesis examines the role of 4E-BP signalling in excitatory forebrain (Camk2a-positive) neurons in behavioural and endocrine responses to acute (ARS) and chronic (CVS) stress, and in ketamine's antidepressant effect. We found that ARS increased grooming and corticosterone in both sexes, with attenuated grooming in male DKO mice only. In CVS, DKO mice showed resilience to stress-induced behavioural deficits, while ketamine reversed these deficits in control mice. This work deepens our understanding of cellular factors controlling stress response and how ketamine produces therapeutic effects.

Name thesis:degree_name

Master of Science (M.Sc.)

Level thesis:degree_level

Master's

Discipline thesis:degree_discipline

Neuroscience

Grantor dc:publisher

Carleton University

Year dc:date.issued

2026

Author dc:creator

• Baranyi Nicholls, Sebastian

Statement dc:rights

• Copyright © 2026 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, distribution to students, research and scholarship. Theses may only be shared by linking to the Carleton University Institutional Repository and no part may be copied without proper attribution to the author; no part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.

Language dc:language.iso

en

DOI

10.22215/etd/2026-17222

OAI identifier oai:identifier

oai:carleton.scholaris.ca:20.500.14718/45379