Postsynaptic Mechanisms of Trophic Factor-Induced Excitatory Synapse Formation in Lymnaea stagnalis
Abstract
Specialized junctions known as synapses, allow neurons to integrate into the functional networks that underlie behaviour (Colon-Ramos, 2009). However, the precise cellular and molecular mechanisms underlying the formation of synapses in the central nervous (CNS) remain largely unknown. In this thesis, I take advantage of the large and individually identifiable neurons of the mollusc Lymnaea stagnalis to study chemical synaptogenesis. In Part One, I present the first direct evidence that activation of the MAPK/ERK cascade is required for the expression of excitatory nicotinic acetylcholine receptors (nAChRs). I further demonstrate that activation of MAPK/ERK by growth factors, may lead to the expression of the transcription factor, menin, a tumor suppressor encoded by the multiple endocrine neoplasia type I (MEN1) gene. I have discovered a novel role for menin, by demonstrating that it is sufficient to induce the expression of excitatory nAChRs in the postsynaptic neuron, left pedal dorsal 1 (LPeD1). In Part Two of my thesis, I explore a novel role for Src family kinases (SFKs) in the CNS, where they appear to be required for the clustering of nAChRs at the synaptic contact site between the presynaptic cell, visceral dorsal 4 (VD4), and postsynaptic cell, LPeD1. While SFKs are known to play a role in the stabilisation of clusters of nAChRs at the neuromuscular junction (Sadasivam et al., 2005), this is the first time that such a phenomenon has been demonstrated in the CNS. While these findings have increased our knowledge of synaptogenesis in Lymnaea, there is potential to extend these discoveries to vertebrate systems as well, due to the fact that there are many synaptic features that have been conserved across evolution (Sheng and Kim, 2011; Chia et al., 2013). While little is known about the mechanisms governing the expression and localisation of nAChRs (Rosenberg et al., 2002; Gaimarri et al., 2007), it is understood that cholinergic systems have been linked to Alzheimer’s disease, as well as certain forms of epilepsy and schizophrenia (Rosenberg et al., 2002). As such, the discoveries I have made regarding the expression and localisation of nAChRs may eventually guide us towards a better understanding of cholinergic-related synaptopathies in the brain.
Description
Keywords
Biology--Cell, Biology--Molecular, Neuroscience, Physiology
Citation
Flynn, N. (2015). Postsynaptic Mechanisms of Trophic Factor-Induced Excitatory Synapse Formation in Lymnaea stagnalis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27390