Perineuronal Net Receptor PTPσ Regulates Retention of Memories
Perineuronal nets (PNNs) have an important physiological role in the retention of learning by restricting cognitive flexibility. Their deposition peaks after developmental periods of intensive learning, usually in late childhood, and they help in long-term preservation of newly acquired skills and i...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Synaptic Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnsyn.2021.672475/full |
| _version_ | 1818905854647205888 |
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| author | Angelina Lesnikova Plinio Casarotto Rafael Moliner Senem Merve Fred Caroline Biojone Eero Castrén |
| author_facet | Angelina Lesnikova Plinio Casarotto Rafael Moliner Senem Merve Fred Caroline Biojone Eero Castrén |
| author_sort | Angelina Lesnikova |
| collection | DOAJ |
| description | Perineuronal nets (PNNs) have an important physiological role in the retention of learning by restricting cognitive flexibility. Their deposition peaks after developmental periods of intensive learning, usually in late childhood, and they help in long-term preservation of newly acquired skills and information. Modulation of PNN function by various techniques enhances plasticity and regulates the retention of memories, which may be beneficial when memory persistence entails negative symptoms such as post-traumatic stress disorder (PTSD). In this study, we investigated the role of PTPσ [receptor-type tyrosine-protein phosphatase S, a phosphatase that is activated by binding of chondroitin sulfate proteoglycans (CSPGs) from PNNs] in retention of memories using Novel Object Recognition and Fear Conditioning models. We observed that mice haploinsufficient for PTPRS gene (PTPσ+/–), although having improved short-term object recognition memory, display impaired long-term memory in both Novel Object Recognition and Fear Conditioning paradigm, as compared to WT littermates. However, PTPσ+/– mice did not show any differences in behavioral tests that do not heavily rely on cognitive flexibility, such as Elevated Plus Maze, Open Field, Marble Burying, and Forced Swimming Test. Since PTPσ has been shown to interact with and dephosphorylate TRKB, we investigated activation of this receptor and its downstream pathways in limbic areas known to be associated with memory. We found that phosphorylation of TRKB and PLCγ are increased in the hippocampus, prefrontal cortex, and amygdaloid complex of PTPσ+/– mice, but other TRKB-mediated signaling pathways are not affected. Our data suggest that PTPσ downregulation promotes TRKB phosphorylation in different brain areas, improves short-term memory performance but disrupts long-term memory retention in the tested animal models. Inhibition of PTPσ or disruption of PNN-PTPσ-TRKB complex might be a potential target for disorders where negative modulation of the acquired memories can be beneficial. |
| first_indexed | 2024-12-19T21:29:57Z |
| format | Article |
| id | doaj.art-03f5fb0774d44aa4a2294dc29547f850 |
| institution | Directory Open Access Journal |
| issn | 1663-3563 |
| language | English |
| last_indexed | 2024-12-19T21:29:57Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Synaptic Neuroscience |
| spelling | doaj.art-03f5fb0774d44aa4a2294dc29547f8502022-12-21T20:04:56ZengFrontiers Media S.A.Frontiers in Synaptic Neuroscience1663-35632021-07-011310.3389/fnsyn.2021.672475672475Perineuronal Net Receptor PTPσ Regulates Retention of MemoriesAngelina LesnikovaPlinio CasarottoRafael MolinerSenem Merve FredCaroline BiojoneEero CastrénPerineuronal nets (PNNs) have an important physiological role in the retention of learning by restricting cognitive flexibility. Their deposition peaks after developmental periods of intensive learning, usually in late childhood, and they help in long-term preservation of newly acquired skills and information. Modulation of PNN function by various techniques enhances plasticity and regulates the retention of memories, which may be beneficial when memory persistence entails negative symptoms such as post-traumatic stress disorder (PTSD). In this study, we investigated the role of PTPσ [receptor-type tyrosine-protein phosphatase S, a phosphatase that is activated by binding of chondroitin sulfate proteoglycans (CSPGs) from PNNs] in retention of memories using Novel Object Recognition and Fear Conditioning models. We observed that mice haploinsufficient for PTPRS gene (PTPσ+/–), although having improved short-term object recognition memory, display impaired long-term memory in both Novel Object Recognition and Fear Conditioning paradigm, as compared to WT littermates. However, PTPσ+/– mice did not show any differences in behavioral tests that do not heavily rely on cognitive flexibility, such as Elevated Plus Maze, Open Field, Marble Burying, and Forced Swimming Test. Since PTPσ has been shown to interact with and dephosphorylate TRKB, we investigated activation of this receptor and its downstream pathways in limbic areas known to be associated with memory. We found that phosphorylation of TRKB and PLCγ are increased in the hippocampus, prefrontal cortex, and amygdaloid complex of PTPσ+/– mice, but other TRKB-mediated signaling pathways are not affected. Our data suggest that PTPσ downregulation promotes TRKB phosphorylation in different brain areas, improves short-term memory performance but disrupts long-term memory retention in the tested animal models. Inhibition of PTPσ or disruption of PNN-PTPσ-TRKB complex might be a potential target for disorders where negative modulation of the acquired memories can be beneficial.https://www.frontiersin.org/articles/10.3389/fnsyn.2021.672475/fullmemoryperineuronal netsplasticityPNNsPTPRSBDNF |
| spellingShingle | Angelina Lesnikova Plinio Casarotto Rafael Moliner Senem Merve Fred Caroline Biojone Eero Castrén Perineuronal Net Receptor PTPσ Regulates Retention of Memories Frontiers in Synaptic Neuroscience memory perineuronal nets plasticity PNNs PTPRS BDNF |
| title | Perineuronal Net Receptor PTPσ Regulates Retention of Memories |
| title_full | Perineuronal Net Receptor PTPσ Regulates Retention of Memories |
| title_fullStr | Perineuronal Net Receptor PTPσ Regulates Retention of Memories |
| title_full_unstemmed | Perineuronal Net Receptor PTPσ Regulates Retention of Memories |
| title_short | Perineuronal Net Receptor PTPσ Regulates Retention of Memories |
| title_sort | perineuronal net receptor ptpσ regulates retention of memories |
| topic | memory perineuronal nets plasticity PNNs PTPRS BDNF |
| url | https://www.frontiersin.org/articles/10.3389/fnsyn.2021.672475/full |
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