Investigating the Role of NMDA Receptor Activity in Neural Circuit Remodeling and Gene Expression in Xenopus Laevis

• Main Author: Schultz, Andrew T
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2021
• Subjects: Albinism; Animal cognition; Behavioral Sciences; Binding sites; Bioinformatics; Biology; Brain research; Brain-derived neurotrophic factor; Desegregation; Frogs; Gene expression; Genetics; Morphology; Neurons; Neurosciences; Ophthalmology; Optic nerve; Physiology; Polymerization; Retina; Signal transduction
• ISBN: 9798841572404

Functions of the nervous system are predicated on the development of precisely organized neural circuitries that enable the transduction of sensory information into internal representations of the environment. This structure-function relationship is exemplified in topographically organized sensory maps. As sensory maps mature during development, their connectivity becomes dictated by patterns of neuronal activity. Integral to activity-dependent plasticity is the glutamatergic NMDA receptor (NMDAR), the gating of which serves as a detector of coincident pre- and postsynaptic activity to mediate plasticity. To study the role of NMDARs in plasticity, our lab utilizes the pharmacological application of the receptor co-agonist D-serine. D-serine rearing has previously been shown to acutely augment NMDAR conductance, and chronically promote synapse maturation and NMDAR-dependent presynaptic axonal arbor stabilization in the Xenopus laevis retinotectal circuit. To strengthen our model, I have sought to clarify the mechanisms by which D-serine drives presynaptic axonal arbor stabilization and gene expression in the Xenopus brain. Experimental results suggest that chronic D-serine treatment promotes presynaptic arbor stabilization by acting on postsynaptic NMDARs but may be doing so in parallel with an NMDAR-independent signaling pathway. Additionally, transcriptomic analyses of brain tissue mRNA indicate that chronic D-serine rearing induces broad changes in gene expression, as does chronic NMDAR antagonism, many of which have been implicated in plasticity. To our surprise, chronic D-serine and NMDAR antagonist treatment also converge on a subset of genes, revealing an unexpected degree of coregulation of gene products downstream of both putative NMDAR augmentation and blockade