Ablation of the Presynaptic Protein Mover Impairs Learning Performance and Decreases Anxiety Behavior in Mice
Abstract
:1. Introduction
2. Results
2.1. Impaired Recognition Memory in Mover Knockout Mice
2.2. Reduced Anxiety Behavior in MOVER Knockout Mice
3. Discussion
4. Materials and Methods
4.1. Mover Knockout Mice
4.2. Behavior Testing
4.3. Elevated Plus Maze
4.4. Open Field
4.5. Novel Object Recognition Task
4.6. Cross Maze
4.7. Morris Water Maze
4.8. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Annamneedi, A.; Caliskan, G.; Muller, S.; Montag, D.; Budinger, E.; Angenstein, F.; Fejtova, A.; Tischmeyer, W.; Gundelfinger, E.D.; Stork, O. Ablation of the presynaptic organizer Bassoon in excitatory neurons retards dentate gyrus maturation and enhances learning performance. Brain Struct. Funct. 2018, 223, 3423–3445. [Google Scholar] [CrossRef] [PubMed]
- Sudhof, T.C. A molecular machine for neurotransmitter release: Synaptotagmin and beyond. Nat. Med. 2013, 19, 1227–1231. [Google Scholar] [CrossRef] [PubMed]
- Kremer, T.; Kempf, C.; Wittenmayer, N.; Nawrotzki, R.; Kuner, T.; Kirsch, J.; Dresbach, T. Mover is a novel vertebrate-specific presynaptic protein with differential distribution at subsets of CNS synapses. FEBS Lett. 2007, 581, 4727–4733. [Google Scholar] [CrossRef]
- Ahmed, S.; Wittenmayer, N.; Kremer, T.; Hoeber, J.; Kiran Akula, A.; Urlaub, H.; Islinger, M.; Kirsch, J.; Dean, C.; Dresbach, T. Mover is a homomeric phospho-protein present on synaptic vesicles. PLoS ONE 2013, 8, e63474. [Google Scholar] [CrossRef]
- Burre, J.; Beckhaus, T.; Corvey, C.; Karas, M.; Zimmermann, H.; Volknandt, W. Synaptic vesicle proteins under conditions of rest and activation: Analysis by 2-D difference gel electrophoresis. Electrophoresis 2006, 27, 3488–3496. [Google Scholar] [CrossRef] [PubMed]
- Antonini, D.; Dentice, M.; Mahtani, P.; De Rosa, L.; Della Gatta, G.; Mandinova, A.; Salvatore, D.; Stupka, E.; Missero, C. Tprg, a gene predominantly expressed in skin, is a direct target of the transcription factor p63. J. Investig. Dermatol. 2008, 128, 1676–1685. [Google Scholar] [CrossRef]
- Wallrafen, R.; Dresbach, T. The Presynaptic Protein Mover Is Differentially Expressed Across Brain Areas and Synapse Types. Front. Neuroanat. 2018, 12, 58. [Google Scholar] [CrossRef] [PubMed]
- Pofantis, E.; Neher, E.; Dresbach, T. Regulation of a subset of release-ready vesicles by the presynaptic protein Mover. Proc. Natl. Acad. Sci. USA 2021, 118, e2022551118. [Google Scholar] [CrossRef]
- Viotti, J.S.; Dresbach, T. Differential Effect on Hippocampal Synaptic Facilitation by the Presynaptic Protein Mover. Front. Synaptic Neurosci. 2019, 11, 30. [Google Scholar] [CrossRef]
- Gilbert, P.E.; Kesner, R.P. The role of the dorsal CA3 hippocampal subregion in spatial working memory and pattern separation. Behav. Brain Res. 2006, 169, 142–149. [Google Scholar] [CrossRef]
- Kesner, R.P. Behavioral functions of the CA3 subregion of the hippocampus. Learn. Mem. 2007, 14, 771–781. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.; Ramirez, S.; Tonegawa, S. Inception of a false memory by optogenetic manipulation of a hippocampal memory engram. Philos. Trans. R Soc. Lond B Biol. Sci. 2014, 369, 20130142. [Google Scholar] [CrossRef] [PubMed]
- Lara, A.H.; Wallis, J.D. The Role of Prefrontal Cortex in Working Memory: A Mini Review. Front. Syst. Neurosci. 2015, 9, 173. [Google Scholar] [CrossRef] [PubMed]
- Schwegler, H.; Crusio, W.E.; Brust, I. Hippocampal mossy fibers and radial-maze learning in the mouse: A correlation with spatial working memory but not with non-spatial reference memory. Neuroscience 1990, 34, 293–298. [Google Scholar] [CrossRef]
- Hagena, H.; Manahan-Vaughan, D. Frequency facilitation at mossy fiber-CA3 synapses of freely behaving rats contributes to the induction of persistent LTD via an adenosine-A1 receptor-regulated mechanism. Cereb. Cortex 2010, 20, 1121–1130. [Google Scholar] [CrossRef]
- Bannerman, D.M.; Sprengel, R.; Sanderson, D.J.; McHugh, S.B.; Rawlins, J.N.; Monyer, H.; Seeburg, P.H. Hippocampal synaptic plasticity, spatial memory and anxiety. Nat. Rev. Neurosci. 2014, 15, 181–192. [Google Scholar] [CrossRef]
- Powell, C.M. Gene targeting of presynaptic proteins in synaptic plasticity and memory: Across the great divide. Neurobiol. Learn. Mem. 2006, 85, 2–15. [Google Scholar] [CrossRef]
- Powell, C.M.; Schoch, S.; Monteggia, L.; Barrot, M.; Matos, M.F.; Feldmann, N.; Sudhof, T.C.; Nestler, E.J. The presynaptic active zone protein RIM1alpha is critical for normal learning and memory. Neuron 2004, 42, 143–153. [Google Scholar] [CrossRef]
- Gundelfinger, E.D.; Reissner, C.; Garner, C.C. Role of Bassoon and Piccolo in Assembly and Molecular Organization of the Active Zone. Front. Synaptic Neurosci. 2015, 7, 19. [Google Scholar] [CrossRef]
- Wang, X.; Hu, B.; Zieba, A.; Neumann, N.G.; Kasper-Sonnenberg, M.; Honsbein, A.; Hultqvist, G.; Conze, T.; Witt, W.; Limbach, C.; et al. A protein interaction node at the neurotransmitter release site: Domains of Aczonin/Piccolo, Bassoon, CAST, and rim converge on the N-terminal domain of Munc13-1. J. Neurosci. 2009, 29, 12584–12596. [Google Scholar] [CrossRef] [Green Version]
- Lueptow, L.M. Novel Object Recognition Test for the Investigation of Learning and Memory in Mice. J. Vis. Exp. 2017, 126, e55718. [Google Scholar] [CrossRef] [PubMed]
- Dere, E.; Huston, J.P.; De Souza Silva, M.A. The pharmacology, neuroanatomy and neurogenetics of one-trial object recognition in rodents. Neurosci. Biobehav. Rev. 2007, 31, 673–704. [Google Scholar] [CrossRef] [PubMed]
- Balderas, I.; Rodriguez-Ortiz, C.J.; Bermudez-Rattoni, F. Retrieval and reconsolidation of object recognition memory are independent processes in the perirhinal cortex. Neuroscience 2013, 253, 398–405. [Google Scholar] [CrossRef] [PubMed]
- Brown, M.W.; Barker, G.R.; Aggleton, J.P.; Warburton, E.C. What pharmacological interventions indicate concerning the role of the perirhinal cortex in recognition memory. Neuropsychologia 2012, 50, 3122–3140. [Google Scholar] [CrossRef]
- Moore, S.J.; Deshpande, K.; Stinnett, G.S.; Seasholtz, A.F.; Murphy, G.G. Conversion of short-term to long-term memory in the novel object recognition paradigm. Neurobiol. Learn. Mem. 2013, 105, 174–185. [Google Scholar] [CrossRef]
- Warburton, E.C.; Brown, M.W. Findings from animals concerning when interactions between perirhinal cortex, hippocampus and medial prefrontal cortex are necessary for recognition memory. Neuropsychologia 2010, 48, 2262–2272. [Google Scholar] [CrossRef]
- Nitta, A.; Izuo, N.; Hamatani, K.; Inagaki, R.; Kusui, Y.; Fu, K.; Asano, T.; Torii, Y.; Habuchi, C.; Sekiguchi, H.; et al. Schizophrenia-Like Behavioral Impairments in Mice with Suppressed Expression of Piccolo in the Medial Prefrontal Cortex. J. Pers. Med. 2021, 11, 607. [Google Scholar] [CrossRef]
- Polissidis, A.; Zelelak, S.; Nikita, M.; Alexakos, P.; Stasinopoulou, M.; Kakazanis, Z.I.; Kostomitsopoulos, N. Assessing the exploratory and anxiety-related behaviors of mice. Do different caging systems affect the outcome of behavioral tests? Physiol. Behav. 2017, 177, 68–73. [Google Scholar] [CrossRef]
- Bhagya, V.R.; Srikumar, B.N.; Veena, J.; Shankaranarayana Rao, B.S. Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits. J. Neurosci. Res. 2017, 95, 1602–1610. [Google Scholar] [CrossRef]
- Bredewold, R.; Veenema, A.H. Sex differences in the regulation of social and anxiety-related behaviors: Insights from vasopressin and oxytocin brain systems. Curr. Opin. Neurobiol. 2018, 49, 132–140. [Google Scholar] [CrossRef]
- Kondo, Y. Lesions of the medial amygdala produce severe impairment of copulatory behavior in sexually inexperienced male rats. Physiol. Behav. 1992, 51, 939–943. [Google Scholar] [CrossRef]
- LeDoux, J.E.; Cicchetti, P.; Xagoraris, A.; Romanski, L.M. The lateral amygdaloid nucleus: Sensory interface of the amygdala in fear conditioning. J. Neurosci. 1990, 10, 1062–1069. [Google Scholar] [CrossRef] [PubMed]
- Clark, D.; Dedova, I.; Cordwell, S.; Matsumoto, I. A proteome analysis of the anterior cingulate cortex gray matter in schizophrenia. Mol. Psychiatry 2006, 11, 459–470. [Google Scholar] [CrossRef] [PubMed]
- Katrancha, S.M.; Koleske, A.J. SNARE Complex Dysfunction: A Unifying Hypothesis for Schizophrenia. Biol. Psychiatry 2015, 78, 356–358. [Google Scholar] [CrossRef]
- O’Donovan, S.M.; Sullivan, C.R.; McCullumsmith, R.E. The role of glutamate transporters in the pathophysiology of neuropsychiatric disorders. npj Schizophr. 2017, 3, 32. [Google Scholar] [CrossRef]
- Akula, A.K.; Zhang, X.; Viotti, J.S.; Nestvogel, D.; Rhee, J.S.; Ebrecht, R.; Reim, K.; Wouters, F.; Liepold, T.; Jahn, O.; et al. The Calmodulin Binding Region of the Synaptic Vesicle Protein Mover Is Required for Homomeric Interaction and Presynaptic Targeting. Front. Mol. Neurosci. 2019, 12, 249. [Google Scholar] [CrossRef]
- Kraeuter, A.K.; Guest, P.C.; Sarnyai, Z. The Elevated Plus Maze Test for Measuring Anxiety-Like Behavior in Rodents. Methods Mol. Biol. 2019, 1916, 69–74. [Google Scholar] [CrossRef]
- Lopez-Noguerola, J.S.; Giessen, N.M.E.; Ueberuck, M.; Meissner, J.N.; Pelgrim, C.E.; Adams, J.; Wirths, O.; Bouter, Y.; Bayer, T.A. Synergistic Effect on Neurodegeneration by N-Truncated Abeta4-42 and Pyroglutamate Abeta3-42 in a Mouse Model of Alzheimer’s Disease. Front. Aging Neurosci. 2018, 10, 64. [Google Scholar] [CrossRef]
- Karl, T.; Pabst, R.; von Horsten, S. Behavioral phenotyping of mice in pharmacological and toxicological research. Exp. Toxicol. Pathol. 2003, 55, 69–83. [Google Scholar] [CrossRef]
- Sestakova, N.; Puzserova, A.; Kluknavsky, M.; Bernatova, I. Determination of motor activity and anxiety-related behaviour in rodents: Methodological aspects and role of nitric oxide. Interdiscip. Toxicol. 2013, 6, 126–135. [Google Scholar] [CrossRef] [Green Version]
- Antunes, M.; Biala, G. The novel object recognition memory: Neurobiology, test procedure, and its modifications. Cogn. Process. 2012, 13, 93–110. [Google Scholar] [CrossRef] [PubMed]
- Jawhar, S.; Trawicka, A.; Jenneckens, C.; Bayer, T.A.; Wirths, O. Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal Abeta aggregation in the 5XFAD mouse model of Alzheimer’s disease. Neurobiol. Aging 2012, 33, 196.e129–196.e140. [Google Scholar] [CrossRef] [PubMed]
- Cleal, M.; Fontana, B.D.; Ranson, D.C.; McBride, S.D.; Swinny, J.D.; Redhead, E.S.; Parker, M.O. The Free-movement pattern Y-maze: A cross-species measure of working memory and executive function. Behav. Res. Methods 2021, 53, 536–557. [Google Scholar] [CrossRef] [PubMed]
- Bouter, Y.; Dietrich, K.; Wittnam, J.L.; Rezaei-Ghaleh, N.; Pillot, T.; Papot-Couturier, S.; Lefebvre, T.; Sprenger, F.; Wirths, O.; Zweckstetter, M.; et al. N-truncated amyloid beta (Abeta) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits. Acta Neuropathol. 2013, 126, 189–205. [Google Scholar] [CrossRef] [PubMed]
- Curdt, N.; Schmitt, F.W.; Bouter, C.; Iseni, T.; Weile, H.C.; Altunok, B.; Beindorff, N.; Bayer, T.A.; Cooke, M.B.; Bouter, Y. Search strategy analysis of Tg4-42 Alzheimer Mice in the Morris Water Maze reveals early spatial navigation deficits. Sci. Rep. 2022, 12, 5451. [Google Scholar] [CrossRef]
- Cooke, M.B.; O’Leary, T.P.; Harris, P.; Ma, R.; Brown, R.E.; Snyder, J.S. Pathfinder: Open source software for analyzing spatial navigation search strategies. F1000Research 2019, 8, 1521. [Google Scholar] [CrossRef] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Schleicher, E.M.; Bayer, T.A.; Iseni, T.; Ott, F.W.; Wagner, J.M.; Viotti, J.S.; Dresbach, T.; Bouter, Y. Ablation of the Presynaptic Protein Mover Impairs Learning Performance and Decreases Anxiety Behavior in Mice. Int. J. Mol. Sci. 2022, 23, 11159. https://doi.org/10.3390/ijms231911159
Schleicher EM, Bayer TA, Iseni T, Ott FW, Wagner JM, Viotti JS, Dresbach T, Bouter Y. Ablation of the Presynaptic Protein Mover Impairs Learning Performance and Decreases Anxiety Behavior in Mice. International Journal of Molecular Sciences. 2022; 23(19):11159. https://doi.org/10.3390/ijms231911159
Chicago/Turabian StyleSchleicher, Eva Maria, Thomas A. Bayer, Trendelina Iseni, Frederik Wilhelm Ott, Jannek Moritz Wagner, Julio S. Viotti, Thomas Dresbach, and Yvonne Bouter. 2022. "Ablation of the Presynaptic Protein Mover Impairs Learning Performance and Decreases Anxiety Behavior in Mice" International Journal of Molecular Sciences 23, no. 19: 11159. https://doi.org/10.3390/ijms231911159