{"id":{"repo_id":"columbia-diss","oai_identifier":"oai:academiccommons.columbia.edu:10.7916/D83N29CX"},"canonical_url":"https://search.dev.ndltd.org/etd/columbia-diss/oai:academiccommons.columbia.edu:10.7916/D83N29CX","repository":{"repo_id":"columbia-diss","name":"Columbia University","base_url":"https://academiccommons.columbia.edu/oai"},"display":{"title":"Novel Small-RNA Mediated Gene Regulatory Mechanisms for Long-Term Memory","abstract":"Memory storage and memory-related synaptic plasticity rely on precise spatiotemporal regulation of gene expression. To explore the role of small RNAs in memory-related synaptic plasticity we carried out massive parallel sequencing to profile the small RNAs of Aplysia. We identified 170 distinct 21-23 nt sized miRNAs, 13 of which were novel and specific to Aplysia. Nine miRNAs were brain-enriched, and several of these were rapidly down-regulated by transient exposure to serotonin, a modulatory neurotransmitter released during learning. Two abundant, and conserved brain-specific miRNAs, miR-124 and miR-22 were exclusively present pre-synaptically in a sensory-motor synapse where they constrain synaptic facilitation through regulation of the transcriptional factor CREB1 and translation factor CPEB respectively. We therefore provide the first evidence that a modulatory neurotransmitter important for learning can regulate the levels of small RNAs and present a novel role for miR-124 and miR-22 in long-term plasticity of synapses in the mature nervous system. While mining the small RNA libraries for miRNAs, we discovered an unexpected and abundant expression in brain of a 28-nt sized class of piRNAs, which had been thought to be germ-line specific. These piRNAs have unique biogenesis patterns and predominant nuclear localization. Moreover, we find that whereas miRNAs are down-regulated by exposure to serotonin, piRNAs are up-regulated. Importantly, we find that the piwi/piRNA complex facilitates serotonin-dependent methylation of a conserved CpG island in the promoter of CREB2, the major inhibitory constraint of memory in Aplysia, leading to the persistence of long-term synaptic facilitation. Taken together, these findings provide a new serotonin-dependent, bidirectional, small-RNA mediated gene regulatory mechanism during plasticity where miRNAs provide translational control and piRNAs provide long-lasting transcriptional control for the persistence of memory.","abstract_html":"Memory storage and memory-related synaptic plasticity rely on precise spatiotemporal regulation of gene expression. To explore the role of small RNAs in memory-related synaptic plasticity we carried out massive parallel sequencing to profile the small RNAs of Aplysia. We identified 170 distinct 21-23 nt sized miRNAs, 13 of which were novel and specific to Aplysia. Nine miRNAs were brain-enriched, and several of these were rapidly down-regulated by transient exposure to serotonin, a modulatory neurotransmitter released during learning. Two abundant, and conserved brain-specific miRNAs, miR-124 and miR-22 were exclusively present pre-synaptically in a sensory-motor synapse where they constrain synaptic facilitation through regulation of the transcriptional factor CREB1 and translation factor CPEB respectively. We therefore provide the first evidence that a modulatory neurotransmitter important for learning can regulate the levels of small RNAs and present a novel role for miR-124 and miR-22 in long-term plasticity of synapses in the mature nervous system. While mining the small RNA libraries for miRNAs, we discovered an unexpected and abundant expression in brain of a 28-nt sized class of piRNAs, which had been thought to be germ-line specific. These piRNAs have unique biogenesis patterns and predominant nuclear localization. Moreover, we find that whereas miRNAs are down-regulated by exposure to serotonin, piRNAs are up-regulated. Importantly, we find that the piwi/piRNA complex facilitates serotonin-dependent methylation of a conserved CpG island in the promoter of CREB2, the major inhibitory constraint of memory in Aplysia, leading to the persistence of long-term synaptic facilitation. Taken together, these findings provide a new serotonin-dependent, bidirectional, small-RNA mediated gene regulatory mechanism during plasticity where miRNAs provide translational control and piRNAs provide long-lasting transcriptional control for the persistence of memory.","abstract_has_math":false,"creators":["Rajasethupathy, Priyamvada"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012","date_published":"2012","updated_at":"2026-07-24T01:44:16Z","subjects":["Neurosciences"],"languages":["English"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.7916/D83N29CX","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Rajasethupathy, Priyamvada"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012"]},{"key":"dc:type","label":"Dc Type","values":["Theses"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Neurosciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.7916/D83N29CX"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Memory storage and memory-related synaptic plasticity rely on precise spatiotemporal regulation of gene expression. To explore the role of small RNAs in memory-related synaptic plasticity we carried out massive parallel sequencing to profile the small RNAs of Aplysia. We identified 170 distinct 21-23 nt sized miRNAs, 13 of which were novel and specific to Aplysia. Nine miRNAs were brain-enriched, and several of these were rapidly down-regulated by transient exposure to serotonin, a modulatory neurotransmitter released during learning. Two abundant, and conserved brain-specific miRNAs, miR-124 and miR-22 were exclusively present pre-synaptically in a sensory-motor synapse where they constrain synaptic facilitation through regulation of the transcriptional factor CREB1 and translation factor CPEB respectively. We therefore provide the first evidence that a modulatory neurotransmitter important for learning can regulate the levels of small RNAs and present a novel role for miR-124 and miR-22 in long-term plasticity of synapses in the mature nervous system. While mining the small RNA libraries for miRNAs, we discovered an unexpected and abundant expression in brain of a 28-nt sized class of piRNAs, which had been thought to be germ-line specific. These piRNAs have unique biogenesis patterns and predominant nuclear localization. Moreover, we find that whereas miRNAs are down-regulated by exposure to serotonin, piRNAs are up-regulated. Importantly, we find that the piwi/piRNA complex facilitates serotonin-dependent methylation of a conserved CpG island in the promoter of CREB2, the major inhibitory constraint of memory in Aplysia, leading to the persistence of long-term synaptic facilitation. Taken together, these findings provide a new serotonin-dependent, bidirectional, small-RNA mediated gene regulatory mechanism during plasticity where miRNAs provide translational control and piRNAs provide long-lasting transcriptional control for the persistence of memory."]},{"key":"dc:title","label":"Title","values":["Novel Small-RNA Mediated Gene Regulatory Mechanisms for Long-Term Memory"]}]}],"canonical_facts":{"dc:creator":["Rajasethupathy, Priyamvada"],"dc:date":["2012"],"dc:description":["Memory storage and memory-related synaptic plasticity rely on precise spatiotemporal regulation of gene expression. To explore the role of small RNAs in memory-related synaptic plasticity we carried out massive parallel sequencing to profile the small RNAs of Aplysia. We identified 170 distinct 21-23 nt sized miRNAs, 13 of which were novel and specific to Aplysia. Nine miRNAs were brain-enriched, and several of these were rapidly down-regulated by transient exposure to serotonin, a modulatory neurotransmitter released during learning. Two abundant, and conserved brain-specific miRNAs, miR-124 and miR-22 were exclusively present pre-synaptically in a sensory-motor synapse where they constrain synaptic facilitation through regulation of the transcriptional factor CREB1 and translation factor CPEB respectively. We therefore provide the first evidence that a modulatory neurotransmitter important for learning can regulate the levels of small RNAs and present a novel role for miR-124 and miR-22 in long-term plasticity of synapses in the mature nervous system. While mining the small RNA libraries for miRNAs, we discovered an unexpected and abundant expression in brain of a 28-nt sized class of piRNAs, which had been thought to be germ-line specific. These piRNAs have unique biogenesis patterns and predominant nuclear localization. Moreover, we find that whereas miRNAs are down-regulated by exposure to serotonin, piRNAs are up-regulated. Importantly, we find that the piwi/piRNA complex facilitates serotonin-dependent methylation of a conserved CpG island in the promoter of CREB2, the major inhibitory constraint of memory in Aplysia, leading to the persistence of long-term synaptic facilitation. Taken together, these findings provide a new serotonin-dependent, bidirectional, small-RNA mediated gene regulatory mechanism during plasticity where miRNAs provide translational control and piRNAs provide long-lasting transcriptional control for the persistence of memory."],"dc:identifier":["https://doi.org/10.7916/D83N29CX"],"dc:language":["English"],"dc:subject":["Neurosciences"],"dc:title":["Novel Small-RNA Mediated Gene Regulatory Mechanisms for Long-Term Memory"],"dc:type":["Theses"]},"updated_at":"2026-07-24T01:44:16Z"}