BMC Neuroscience | |
NF-κB p50 subunit knockout impairs late LTP and alters long term memory in the mouse hippocampus | |
Benedict C Albensi3  Michael J Bernstein1  Avril Hatherell2  Melanie Neuendorff2  Eric Platt2  Gary L Odero2  Kensuke Oikawa2  | |
[1] Dept. of Psychological and Social Sciences, Pennsylvania State University, Abington, PA, USA;Div’n. of Neurodegenerative Disorders, St. Boniface Hospital Research, Winnipeg, MB, Canada;St. Boniface Research Ctr., 351 Tache Ave. / R4050, Winnipeg, MB, R2H 2A6, Canada | |
关键词: Memory; Transcription; LTP; Water maze; NF-kappa B; Hippocampus; | |
Others : 1170741 DOI : 10.1186/1471-2202-13-45 |
|
received in 2012-03-06, accepted in 2012-05-03, 发布年份 2012 | |
【 摘 要 】
Background
Nuclear factor kappa B (NF-κB) is a transcription factor typically expressed with two specific subunits (p50, p65). Investigators have reported that NF-κB is activated during the induction of in vitro long term potentiation (LTP), a paradigm of synaptic plasticity and correlate of memory, suggesting that NF-κB may be necessary for some aspects of memory encoding. Furthermore, NF-κB has been implicated as a potential requirement in behavioral tests of memory. Unfortunately, very little work has been done to explore the effects of deleting specific NF-κB subunits on memory. Studies have shown that NF-κB p50 subunit deletion (p50−/−) leads to memory deficits, however some recent studies suggest the contrary where p50−/− mice show enhanced memory in the Morris water maze (MWM). To more critically explore the role of the NF-κB p50 subunit in synaptic plasticity and memory, we assessed long term spatial memory in vivo using the MWM, and synaptic plasticity in vitro utilizing high frequency stimuli capable of eliciting LTP in slices from the hippocampus of NF-κB p50−/− versus their controls (p50+/+).
Results
We found that the lack of the NF-κB p50 subunit led to significant decreases in late LTP and in selective but significant alterations in MWM tests (i.e., some improvements during acquisition, but deficits during retention).
Conclusions
These results support the hypothesis that the NF-κ p50 subunit is required in long term spatial memory in the hippocampus.
【 授权许可】
2012 Oikawa et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150417024758570.pdf | 1269KB | download | |
Figure 10. | 40KB | Image | download |
Figure 9. | 76KB | Image | download |
Figure 8. | 42KB | Image | download |
Figure 7. | 22KB | Image | download |
Figure 6. | 25KB | Image | download |
Figure 5. | 31KB | Image | download |
Figure 4. | 25KB | Image | download |
Figure 3. | 42KB | Image | download |
Figure 2. | 29KB | Image | download |
Figure 1. | 22KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Figure 7.
Figure 8.
Figure 9.
Figure 10.
【 参考文献 】
- [1]Freudenthal R, Romano A: Participation of Rel/NF-kappaB transcription factors in long-term memory in the crab Chasmagnathus. Brain Res 2000, 855(2):274-281.
- [2]Meberg PJ, Kinney WR, Valcourt EG, Routtenberg A: Gene expression of the transcription factor NF-kappa B in hippocampus: regulation by synaptic activity. Brain Res Mol Brain Res 1996, 38(2):179-190.
- [3]Kassed CA, Willing AE, Garbuzova-Davis S, Sanberg PR, Pennypacker KR: Lack of NF-kappaB p50 exacerbates degeneration of hippocampal neurons after chemical exposure and impairs learning. Exp Neurol 2002, 176(2):277-288.
- [4]Freudenthal R, Romano A, Routtenberg A: Transcription factor NF-kappaB activation after in vivo perforant path LTP in mouse hippocampus. Hippocampus 2004, 14(6):677-683.
- [5]Albensi BC, Mattson MP: Evidence for the involvement of TNF and NF-kappaB in hippocampal synaptic plasticity. Synapse 2000, 35(2):151-159.
- [6]Denis-Donini S, Dellarole A, Crociara P, Francese MT, Bortolotto V, Quadrato G, Canonico PL, Orsetti M, Ghi P, Memo M, et al.: Impaired adult neurogenesis associated with short-term memory defects in NF-kappaB p50-deficient mice. J Neurosci 2008, 28(15):3911-3919.
- [7]O’Riordan KJ, Huang IC, Pizzi M, Spano P, Boroni F, Egli R, Desai P, Fitch O, Malone L, Ahn HJ, et al.: Regulation of nuclear factor kappaB in the hippocampus by group I metabotropic glutamate receptors. J Neurosci 2006, 26(18):4870-4879.
- [8]Ahn HJ, Hernandez C, Levenson JM, Lubin FD, Liou HC, Sweatt JD: c-Rel, an NF-kappaB family transcription factor, is required for hippocampal long-term synaptic plasticity and memory formation. Learn Mem 2008, 15(7):539-549.
- [9]O’Sullivan NC, Croydon L, McGettigan PA, Pickering M, Murphy KJ: Hippocampal region-specific regulation of NF-kappaB may contribute to learning-associated synaptic reorganisation. Brain Res Bull 2010, 81(4–5):385-390.
- [10]Kaltschmidt B, Ndiaye D, Korte M, Pothion S, Arbibe L, Prullage M, Pfeiffer J, Lindecke A, Staiger V, Israel A, et al.: NF-kappaB regulates spatial memory formation and synaptic plasticity through protein kinase A/CREB signaling. Mol Cell Biol 2006, 26(8):2936-2946.
- [11]Tse MT: Synaptic plasticity: adding a piece to the LTP jigsaw. Nat Rev Neurosci 2012, 13(3):150-151.
- [12]Lisman J, Grace AA, Duzel E: A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP. Trends Neurosci 2011, 34(10):536-547.
- [13]De Roo M, Klauser P, Garcia PM, Poglia L, Muller D: Spine dynamics and synapse remodeling during LTP and memory processes. Prog Brain Res 2008, 169:199-207.
- [14]Vlachos A, Maggio N, Jedlicka P: Just in time for late-LTP: a mechanism for the role of PKMzeta in long-term memory. Commun Integr Biol 2008, 1(2):190-191.
- [15]Appleby PA, Kempermann G, Wiskott L: The role of additive neurogenesis and synaptic plasticity in a hippocampal memory model with grid-cell like input. PLoS Comput Biol 2011, 7(1):e1001063.
- [16]Bramham CR: Local protein synthesis, actin dynamics, and LTP consolidation. Curr Opin Neurobiol 2008, 18(5):524-531.
- [17]Abraham WC, Williams JM: Properties and mechanisms of LTP maintenance. Neuroscientist 2003, 9(6):463-474.
- [18]Abraham WC, Williams JM: LTP maintenance and its protein synthesis-dependence. Neurobiol Learn Mem 2008, 89(3):260-268.
- [19]Whitlock JR, Heynen AJ, Shuler MG, Bear MF: Learning induces long-term potentiation in the hippocampus. Science 2006, 313(5790):1093-1097.
- [20]Freudenthal R, Locatelli F, Hermitte G, Maldonado H, Lafourcade C, Delorenzi A, Romano A: Kappa-B like DNA-binding activity is enhanced after spaced training that induces long-term memory in the crab Chasmagnathus. Neurosci Lett 1998, 242(3):143-146.
- [21]Yeh SH, Lin CH, Gean PW: Acetylation of nuclear factor-kappaB in rat amygdala improves long-term but not short-term retention of fear memory. Mol Pharmacol 2004, 65(5):1286-1292.
- [22]Kassed CA, Herkenham M: NF-kappaB p50-deficient mice show reduced anxiety-like behaviors in tests of exploratory drive and anxiety. Behav Brain Res 2004, 154(2):577-584.
- [23]Lehmann ML, Brachman RA, Listwak SJ, Herkenham M: NF-kappaB activity affects learning in aversive tasks: possible actions via modulation of the stress axis. Brain Behav Immun 2010, 24(6):1008-1017.
- [24]Sha WC, Liou HC, Tuomanen EI, Baltimore D: Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses. Cell 1995, 80(2):321-330.
- [25]Odero GL, Oikawa K, Glazner KA, Schapansky J, Grossman D, Thiessen JD, Motnenko A, Ge N, Martin M, Glazner GW, et al.: Evidence for the involvement of calbindin D28k in the presenilin 1 model of Alzheimer’s disease. Neuroscience 2010, 169:532-543.
- [26]Glazner KA, Odero GL, Anema E, Motnenko A, Schapansky J, Grossman D, Oliver DR, Glazner GW, Albensi BC: Strain specific differences in memory and neuropathology in a mouse model of Alzheimer’s disease. Life Sci 2010, 86(25–26):942-950.
- [27]Thiessen JD, Collister KA, Kurjewicz LM, Del Bigio MR, ALBENSI BC, Martin M: Magnetic Resonance Imaging and Behavioural Test Comparisons in a Mouse Model of Alzheimer's Disease. Physics in Canada 2007, 63(3):134-137.
- [28]Brody DL, Holtzman DM: Morris water maze search strategy analysis in PDAPP mice before and after experimental traumatic brain injury. Exp Neurol 2006, 197(2):330-340.
- [29]Federico F, Leggio MG, Neri P, Mandolesi L, Petrosini L: NMDA receptor activity in learning spatial procedural strategies II. The influence of cerebellar lesions. Brain Res Bull 2006, 70(4–6):356-367.
- [30]Leggio MG, Federico F, Neri P, Graziano A, Mandolesi L, Petrosini L: NMDA receptor activity in learning spatial procedural strategies I. The influence of hippocampal lesions. Brain Res Bull 2006, 70(4–6):347-355.
- [31]Albensi BC, Alasti N, Mueller AL: Long-term potentiation in the presence of NMDA receptor antagonist arylalkylamine spider toxins. J Neurosci Res 2000, 62(2):177-185.
- [32]Janus C: Search strategies used by APP transgenic mice during navigation in the Morris water maze. Learn Mem 2004, 11(3):337-346.
- [33]Bliss TV, Collingridge GL: A synaptic model of memory: long-term potentiation inthe hippocampus. Nature 1993, 361(6407):31-39.
- [34]Raymond CR: LTP forms 1, 2 and 3: different mechanisms for the “long” in long-term potentiation. Trends Neurosci 2007, 30(4):167-175.
- [35]Amsel A: Hippocampal function in the rat: cognitive mapping or vicarious trial and error? Hippocampus 1993, 3(3):251-256.
- [36]Tolman EC: Cognitive maps in rats and men. Psychol Rev 1948, 55:1-4.
- [37]Levenson JM, Choi S, Lee SY, Cao YA, Ahn HJ, Worley KC, Pizzi M, Liou HC, Sweatt JD: A bioinformatics analysis of memory consolidation reveals involvement of the transcription factor c-rel. J Neurosci 2004, 24(16):3933-3943.
- [38]Kaltschmidt B, Ndiaye D, Korte M, Pothion S, Arbibe L, Prüllage M, Pfeiffer J, Lindecke A, Staiger V, Israël A, Kaltschmidt C, Mémet S: NF-kappaB regulates spatial memory formation and synaptic plasticity through protein kinase A/CREB signaling. Mol Cell Biol 2006, 26(8):2936-2946.
- [39]Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D: NF-kappa B functions in synaptic signaling and behavior. Nat Neurosci 2003, 6(10):1072-1078.
- [40]O’Mahony A, Raber J, Montano M, Foehr E, Han V, Lu SM, Kwon H, LeFevour A, Chakraborty-Sett S, Greene WC: NF-kappaB/Rel regulates inhibitory and excitatory neuronal function and synaptic plasticity. Mol Cell Biol 2006, 26(19):7283-7298.
- [41]Phelps CB, Sengchanthalangsy LL, Malek S, Ghosh G: Mechanism of kappa B DNA binding by Rel/NF-kappa B dimers. J Biol Chem 2000, 275(32):24392-24399.