Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus
In the developing nervous system synaptic refinement, typified by the neuromuscular junction where supernumerary connections are eliminated by axon retraction leaving the postsynaptic target innervated by a single dominant input, critically regulates neuronal circuit formation. Whether such competit...
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Frontiers Research Foundation
2013
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| Online Access: | http://hdl.handle.net/1721.1/77581 https://orcid.org/0000-0003-2839-8228 |
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| author | Lopez, Carla M. Pelkey, Kenneth A. Chittajallu, Ramesh Nakashiba, Toshiaki Toth, Katalin Tonegawa, Susumu McBain, Chris J. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Lopez, Carla M. Pelkey, Kenneth A. Chittajallu, Ramesh Nakashiba, Toshiaki Toth, Katalin Tonegawa, Susumu McBain, Chris J. |
| author_sort | Lopez, Carla M. |
| collection | MIT |
| description | In the developing nervous system synaptic refinement, typified by the neuromuscular junction where supernumerary connections are eliminated by axon retraction leaving the postsynaptic target innervated by a single dominant input, critically regulates neuronal circuit formation. Whether such competition-based pruning continues in established circuits of mature animals remains unknown. This question is particularly relevant in the context of adult neurogenesis where newborn cells must integrate into preexisting circuits, and thus, potentially compete with functionally mature synapses to gain access to their postsynaptic targets. The hippocampus plays an important role in memory formation/retrieval and the dentate gyrus (DG) subfield exhibits continued neurogenesis into adulthood. Therefore, this region contains both mature granule cells (old GCs) and immature recently born GCs that are generated throughout adult life (young GCs), providing a neurogenic niche model to examine the role of competition in synaptic refinement. Recent work from an independent group in developing animals indicated that embryonically/early postnatal generated GCs placed at a competitive disadvantage by selective expression of tetanus toxin (TeTX) to prevent synaptic release rapidly retracted their axons, and that this retraction was driven by competition from newborn GCs lacking TeTX. In contrast, following 3–6 months of selective TeTX expression in old GCs of adult mice we did not observe any evidence of axon retraction. Indeed ultrastructural analyses indicated that the terminals of silenced GCs even maintained synaptic contact with their postsynaptic targets. Furthermore, we did not detect any significant differences in the electrophysiological properties between old GCs in control and TeTX conditions. Thus, our data demonstrate a remarkable stability in the face of a relatively prolonged period of altered synaptic competition between two populations of neurons within the adult brain. |
| first_indexed | 2024-09-23T08:55:49Z |
| format | Article |
| id | mit-1721.1/77581 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:55:49Z |
| publishDate | 2013 |
| publisher | Frontiers Research Foundation |
| record_format | dspace |
| spelling | mit-1721.1/775812022-09-30T12:14:27Z Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus Lopez, Carla M. Pelkey, Kenneth A. Chittajallu, Ramesh Nakashiba, Toshiaki Toth, Katalin Tonegawa, Susumu McBain, Chris J. Massachusetts Institute of Technology. Department of Biology Picower Institute for Learning and Memory RIKEN-MIT Center for Neural Circuit Genetics Nakashiba, Toshiaki Tonegawa, Susumu In the developing nervous system synaptic refinement, typified by the neuromuscular junction where supernumerary connections are eliminated by axon retraction leaving the postsynaptic target innervated by a single dominant input, critically regulates neuronal circuit formation. Whether such competition-based pruning continues in established circuits of mature animals remains unknown. This question is particularly relevant in the context of adult neurogenesis where newborn cells must integrate into preexisting circuits, and thus, potentially compete with functionally mature synapses to gain access to their postsynaptic targets. The hippocampus plays an important role in memory formation/retrieval and the dentate gyrus (DG) subfield exhibits continued neurogenesis into adulthood. Therefore, this region contains both mature granule cells (old GCs) and immature recently born GCs that are generated throughout adult life (young GCs), providing a neurogenic niche model to examine the role of competition in synaptic refinement. Recent work from an independent group in developing animals indicated that embryonically/early postnatal generated GCs placed at a competitive disadvantage by selective expression of tetanus toxin (TeTX) to prevent synaptic release rapidly retracted their axons, and that this retraction was driven by competition from newborn GCs lacking TeTX. In contrast, following 3–6 months of selective TeTX expression in old GCs of adult mice we did not observe any evidence of axon retraction. Indeed ultrastructural analyses indicated that the terminals of silenced GCs even maintained synaptic contact with their postsynaptic targets. Furthermore, we did not detect any significant differences in the electrophysiological properties between old GCs in control and TeTX conditions. Thus, our data demonstrate a remarkable stability in the face of a relatively prolonged period of altered synaptic competition between two populations of neurons within the adult brain. National Institutes of Health (U.S.) (Grant R01-MH078821) National Institutes of Health (U.S.) (Grant P50-MH58880) 2013-03-06T17:59:20Z 2013-03-06T17:59:20Z 2012-11 2012-08 Article http://purl.org/eprint/type/JournalArticle 1662-5110 http://hdl.handle.net/1721.1/77581 Lopez, Carla M. et al. “Competition from Newborn Granule Cells Does Not Drive Axonal Retraction of Silenced Old Granule Cells in the Adult Hippocampus.” Frontiers in Neural Circuits 6 (2012). ©2012 Frontiers Media S. A. https://orcid.org/0000-0003-2839-8228 en_US http://dx.doi.org/10.3389/fncir.2012.00085 Frontiers in Neural Circuits Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Frontiers Research Foundation Frontiers Research Foundation |
| spellingShingle | Lopez, Carla M. Pelkey, Kenneth A. Chittajallu, Ramesh Nakashiba, Toshiaki Toth, Katalin Tonegawa, Susumu McBain, Chris J. Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus |
| title | Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus |
| title_full | Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus |
| title_fullStr | Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus |
| title_full_unstemmed | Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus |
| title_short | Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus |
| title_sort | competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus |
| url | http://hdl.handle.net/1721.1/77581 https://orcid.org/0000-0003-2839-8228 |
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