Uncovering the Cellular and Molecular Mechanisms of Synapse Formation and Functional Specificity Using Central Neurons of Lymnaea stagnalis

Abstract

All functions of the nervous system are contingent upon the precise organization of neuronal connections that are initially patterned during development, and then continually modified throughout life. Determining the mechanisms that specify the formation and functional modulation of synaptic circuitry are critical to advancing both our fundamental understanding of the nervous system as well as the various neurodevelopmental, neurological, neuropsychiatric, and neurodegenerative disorders that are met in clinical practice when these processes go awry. Defining the cellular and molecular mechanisms underlying nervous system development, function, and pathology has proven challenging, due mainly to the complexity of the vertebrate brain. Simple model system approaches with invertebrate preparations, on the other hand, have played pivotal roles in elucidating the fundamental mechanisms underlying the formation and plasticity of individual synapses, and the contributions of individual neurons and their synaptic connections that underlie a variety of behaviors, and learning and memory. In this Review, we discuss the experimental utility of the invertebrate mollusc Lymnaea stagnalis, with a particular emphasis on in vitro cell culture, semi-intact and in vivo preparations, which enable molecular and electrophysiological identification of the cellular and molecular mechanisms governing the formation, plasticity, and specificity of individual synapses at a single-neuron or single-synapse resolution.

Transcriptome analysis provides genome annotation and expression profiles in the central nervous system of Lymnaea stagnalis at different ages

“…L. stagnalis has served as a unique model organism for the study of neural networks, neuronal development, and synapse formation [ 6 , 14 , 16 ] due to its simple, well-characterized, and easily accessible CNS. In addition, it has recently emerged as a useful model for studying brain aging and neurodegenerative diseases [ 22 – 24 ].…”

“…Many studies have used this model to investigate the fundamental mechanisms of neuronal networks involved in various behaviours including feeding [ 4 , 5 ], respiration [ 6 , 7 ], locomotion [ 8 , 9 ], and reproduction [ 10 , 11 ]. Studies have also focused on high cognitive behaviours, including learning and memory [ 12 – 15 ], as well as deciphering cellular mechanisms of synapse formation and synaptic plasticity during development [ 16 – 18 ]. L. stagnalis has also recently gained increasing popularity for the investigation of brain aging and neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease [ 19 – 23 ].…”

Transcriptome analysis provides genome annotation and expression profiles in the central nervous system ofLymnaea stagnalisat different ages

“…L. stagnalis has served as a unique model organism for the study of neural networks, neuronal development, and synapse formation (Getz et al, 2018;Haque et al, 2006;Swinton et al, 2019) due to its simple, well-characterized, and easily accessible CNS. In addition, it has recently emerged as a useful model for studying brain aging and neurodegenerative diseases (Fodor, Urban, et al, 2020;Hermann et al, 2020;Maasz et al, 2017).…”

“…Many studies have used this model to investigate the fundamental mechanisms of neuronal networks involved in various behaviours including feeding (Kojima, Nanakamura, Nagayama, Fujito, & Ito, 1997;Yeoman, Kemenes, Benjamin, & Elliott, 1994), respiration (Haque et al, 2006;Taylor & Lukowiak, 2000), locomotion (Syed & Winlow, 1991;Vorontsov, Tsyganov, & Sakharov, 2004), and reproduction (Hermann, de Lange, Pieneman, ter Maat, & Jansen, 1997;Jimenez et al, 2004). Studies have also focused on high cognitive behaviours, including learning and memory (Dodd, Rothwell, & Lukowiak, 2018;Sunada et al, 2017;Swinton et al, 2019;Tan & Lukowiak, 2018), as well as deciphering cellular mechanisms of synapse formation and synaptic plasticity during development (Getz, Wijdenes, Riaz, & Syed, 2018;Mersman, Jolly, Lin, & Xu, 2020;Onizuka et al, 2012). L. stagnalis has also recently gained increasing popularity for the investigation of brain aging and neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease (Arundell et al, 2006;de Weerd, Hermann, & Wildering, 2017;Ford, Crossley, Vadukul, Kemenes, & Serpell, 2017;Hermann, Perry, Hamad, & Wildering, 2020;Maasz et al, 2017).…”

Tissue-specific evaluation of suitable reference genes for RT-qPCR in the pond snail,Lymnaea stagnalis

“…Previous studies have primarily focused on its neurobiology, as well as its endocrinology, immunology, and shell morphology (Chase, 2002; Benjamin, 2008). The central nervous system (CNS) is relatively simple, with approximately 20,000 neurons, many of which are large and easily identifiable, making them amenable for studies of learning, memory, motor pattern generation, neuronal regeneration, and synapse formation (Lukowiak, 2016; Elliott & Susswein, 2002; Chase, 2002; Lukowiak et al, 2003; Getz et al, 2018). Parallel investigations into the neuroendocrine (Koene, 2010; Pirger et al, 2010) and immune (Van Der Knaap, Adema & Sminia, 1993; Gust et al, 2013a) systems of L. stagnalis and other gastropods have improved our understanding of reproductive behavior, immunity and toxicology of L. stagnalis .…”