Abstract
A key goal in modern neurobiology is to understand the mechanisms underlying learning and memory. To that end, it is essential to identify the patterns of gene expression and the temporal sequence of molecular events associated with learning and memory processes. It is also important to ascertain if and how these molecular events vary between organisms. In vertebrates, learning and memory processes are characterized by distinct phases of molecular activity involving gene transcription, structural change, and long-term maintenance of such structural change in the nervous system. Utilizing next generation sequencing techniques, we profiled the temporal expression patterns of genes in the brain of the fire-bellied toad Bombina orientalis after prey catching conditioning. The fire-bellied toad is a basal tetrapod whose neural architecture and molecular pathways may help us understand the ancestral state of learning and memory mechanisms in tetrapods. Differential gene expression following conditioning revealed activity in molecular pathways related to immediate early genes (IEG), cytoskeletal modification, axon guidance activity, and apoptotic processes. Conditioning induced early IEG activity coinciding with transcriptional activity and neuron structural modification, followed by axon guidance and cell adhesion activity, and late neuronal pruning. While some of these gene expression patterns are similar to those found in mammals submitted to conditioning, some interesting divergent expression profiles were seen, and differential expression of some well-known learning-related mammalian genes is missing altogether. These results highlight the importance of using a comparative approach in the study of the mechanisms of leaning and memory and provide molecular resources for a novel vertebrate model in the relatively poorly studied Amphibia.
Highlights
Defined, learning is the change in behavior that comes as a result of experience (Mackintosh, 1974; Rudy, 2014)
Induction involves activity-dependent Ca+2 second messenger signaling cascades which lead to the recruitment of AMPA receptors to the post-synaptic density, as well as activation of the MAPK-CREB pathway which results in learning-related gene transcription (Kandel, 2012)
Transcriptome assembly resulted in 1,236,332 total transcripts consisting of 656,704,220 biological processes (BP) and 714,091 non-redundant “Trinity” genes
Summary
Defined, learning is the change in behavior that comes as a result of experience (Mackintosh, 1974; Rudy, 2014). Induction involves activity-dependent Ca+2 second messenger signaling cascades which lead to the recruitment of AMPA receptors to the post-synaptic density, as well as activation of the MAPK-CREB pathway which results in learning-related gene transcription (Kandel, 2012). These early memory processes begin the events leading to long-term changes in the strength of synaptic transmission. The maintenance phase involves stabilizing the increase in AMPA receptors at synapses, as well as structural stabilization of synaptic modifications, such as synaptic enlargement (Desmond and Levy, 1986; Stewart et al, 2000; Blitzer, 2005; Rudy, 2015b). While much is known about the molecular pathways underlying vertebrate LTP (Malenka and Bear, 2004), there is still much to be learned especially in terms of the mechanisms underlying maintenance of stored memory
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