Abstract
A major extrinsic factor influencing memory and neuro-cognitive performances across taxa is diet. Studies from vertebrates have shown the effects of a flavonoid rich diet on cognitive performance, but the mechanism underlying this action is still poorly understood. A common and abundant flavonoid present in numerous food substances is quercetin (Q). The present study provides the first support for Q-modulated enhancement of cognitive function in an invertebrate model, the pond snail Lymnaea stagnalis, after an operant conditioning procedure. We found that when snails were exposed to Q 3 h before or after a single 0.5 h training session, which typically results in memory lasting ~ 3 h, they formed a long-term memory (LTM) lasting for at least 24 h. Additionally, we assessed the effects of the combined presentation of a single reinforcing stimulus (at 24 h post-training or 24 h before training) and Q-exposure on both LTM formation and reconsolidation. That is, when applied within 3 h of critical periods of memory, Q regulates four different phases: (1) acquisition (i.e., a learning event), (2) consolidation processes after acquisition, (3) memory recall, and (4) memory reconsolidation. In all these phases Q-exposure enhanced LTM persistence.
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Abbreviations
- CREB:
-
Cyclic AMP response element-binding protein
- HS:
-
Heat stressor
- HSP:
-
Heat-shock protein
- ITM:
-
Intermediate-term memory
- LTM:
-
Long-term memory
- PW:
-
Pond water
- Q:
-
Quercetin
- STM:
-
Short-term memory
- TBT:
-
Total breathing time
References
Ahmad S, Ullah F, Ayaz M, Sadiq A, Imran M (2015) Antioxidant and anticholinesterase investigations of Rumex hastatus D. Don: potential effectiveness in oxidative stress and neurological disorders. Biol Res 48(1):20. https://doi.org/10.1186/s40659-015-0010-2
Alberini CM (2005) Mechanisms of memory stabilization: are consolidation and reconsolidation similar or distinct processes? Trends Neurosci 28:51–56. https://doi.org/10.1016/j.tins.2004.11.001
Alberini CM (2009) Transcription factors in long-term memory and synaptic plasticity. Physiol Rev 89(1):121–145. https://doi.org/10.1152/physrev.00017.2008
Alberini CM (2011) The role of reconsolidation and the dynamic process of long-term memory formation and storage. Front Behav Neurosci 5:12. https://doi.org/10.3389/fnbeh.2011.00012
Anokhin KV, Tiunova AA, Rose SPR (2002) Reminder effects—reconsolidation or retrieval deficit? Pharmacological dissection with protein synthesis inhibitors following reminder for a passive-avoidance task in young chicks: Memory consolidation and reminder effects in chicks. Eur J Neurosci 15:1759–1765. https://doi.org/10.1046/j.1460-9568.2002.02023.x
Ansari MA, Abdul HM, Joshi G, Opii WO, Butterfield DA (2009) Protective effect of quercetin in primary neurons against Abeta(1-42): relevance to Alzheimer’s disease. J Nutr Biochem 20:269–275. https://doi.org/10.1016/j.jnutbio.2008.03.002
Ayaz M, Sadiq A, Junaid M, Ullah F, Ovais M, Ullah I, Ahmed J, Shahid M (2019) Flavonoids as prospective neuroprotectants and their therapeutic propensity in aging associated neurological disorders. Front Aging Neurosci 11:155. https://doi.org/10.3389/fnagi.2019.00155
Bakoyiannis I, Daskalopoulou A, Pergialiotis V, Perrea D (2019) Phytochemicals and cognitive health: are flavonoids doing the trick? Biomed Pharmacother 109:1488–1497. https://doi.org/10.1016/j.biopha.2018.10.086
Barco A, Pittenger C, Kandel ER (2003) CREB, memory enhancement and the treatment of memory disorders: promises, pitfalls and prospects. Expert Opin Ther Targets 7:101–114. https://doi.org/10.1517/14728222.7.1.101
Batabyal A, Lukowiak K (2021) Configural learning memory can be transformed from intermediate-term to long-term in pond snail Lymnaea stagnalis. Physiol Behav 239:113509. https://doi.org/10.1016/j.physbeh.2021.113509
Batabyal A, Rivi V, Benatti C, Blom JMC, Lukowiak K (2021) Long-term memory of configural learning is enhanced via CREB upregulation by the flavonoid quercetin in Lymnaea stagnalis. J Exp Biol 224(13):jeb242761. https://doi.org/10.1242/jeb.242761
Bhutada P, Mundhada Y, Bansod K, Bhutada C, Tawari S, Dixit P, Mundhada D (2010) Ameliorative effect of quercetin on memory dysfunction in streptozotocin-induced diabetic rats. Neurobiol Learn Mem 94:293–302. https://doi.org/10.1016/j.nlm.2010.06.008
Bisaz R, Travaglia A, Alberini CM (2014) The neurobiological bases of memory formation: from physiological conditions to psychopathology. Psychopathology 47:347–356. https://doi.org/10.1159/000363702
Bozon B, Kelly A, Josselyn SA, Silva AJ, Davis S, Laroche S (2003) MAPK, CREB and zif268 are all required for the consolidation of recognition memory. Philos Trans R Soc Lond B 358:805–814. https://doi.org/10.1098/rstb.2002.1224
Braun M, Lukowiak K (2011) Intermediate and long-term memory are different at the neuronal level in Lymnaea stagnalis (L.). Neurobiol Learn Mem 96:403–416. https://doi.org/10.1016/j.nlm.2011.06.016
Broman-Fulks JJ, Canu WH, Trout KL, Nieman DC (2012) The effects of quercetin supplementation on cognitive functioning in a community sample: a randomized, placebo-controlled trial. Ther Adv Psychopharmacol 2:131–138. https://doi.org/10.1177/2045125312445894
Conte C, Herdegen S, Kamal S, Patel J, Patel U, Perez L, Rivota M, Calin-Jageman RJ, Calin-Jageman IE (2017) Transcriptional correlates of memory maintenance following long-term sensitization of Aplysia californica. Learn Mem 24:502–515. https://doi.org/10.1101/lm.045450.117
Cushnie TPT, Lamb AJ (2005) Antimicrobial activity of flavonoids. Int J Antimicrob Agents 26:343–356. https://doi.org/10.1016/j.ijantimicag.2005.09.002
Dalesman S, Lukowiak K (2010) Effect of acute exposure to low environmental calcium on respiration and locomotion in Lymnaea stagnalis (L.). J Exp Biol 213:1471–1476. https://doi.org/10.1242/jeb.040493
Dalesman S, Rundle SD (2010) Influence of rearing and experimental temperatures on predator avoidance behaviour in a freshwater pulmonate snail: temperature and snail behaviour. Freshw Biol 55:2107–2113. https://doi.org/10.1111/j.1365-2427.2010.02470.x
Davis RL (2011) Traces of Drosophila memory. Neuron 70:8–19. https://doi.org/10.1016/j.neuron.2011.03.012
Debiec J, LeDoux JE, Nader K (2002) Cellular and systems reconsolidation in the hippocampus. Neuron 36:527–538. https://doi.org/10.1016/S0896-6273(02)01001-2
Eggler AL, Gay KA, Mesecar AD (2008) Molecular mechanisms of natural products in chemoprevention: induction of cytoprotective enzymes by Nrf2. Mol Nutr Food Res 52(Suppl 1):S84–S94. https://doi.org/10.1002/mnfr.200700249
Fernell M, Swinton C, Lukowiak K (2016) Epicatechin, a component of dark chocolate, enhances memory formation if applied during the memory consolidation period. Commun Integr Biol 9:e1205772. https://doi.org/10.1080/19420889.2016.1205772
Fernell M, Rivi V, Batabyal A, Lukowiak K (2021) The temperature-sensitivity of memory formation and persistence is altered by cold acclimation in a pond snail. J Exp Biol 224(11):jeb242513. https://doi.org/10.1242/jeb.242513
Finkbeiner S, Tavazoie SF, Maloratsky A, Jacobs KM, Harris KM, Greenberg ME (1997) CREB: a major mediator of neuronal neurotrophin responses. Neuron 19:1031–1047. https://doi.org/10.1016/S0896-6273(00)80395-5
Fodor I, Hussein AA, Benjamin PR, Koene JM, Pirger Z (2020) The unlimited potential of the great pond snail, Lymnaea stagnalis. eLife 9:e56962. https://doi.org/10.7554/eLife.56962
Foster NL, Lukowiak K, Henry TB (2015) Time-related expression profiles for heat shock protein gene transcripts (HSP40, HSP70) in the central nervous system of Lymnaea stagnalis exposed to thermal stress. Commun Integr Biol 8(3):e1040954. https://doi.org/10.1080/19420889.2015.1040954
Fruson L, Dalesman S, Lukowiak K (2012) A flavonol present in cocoa [(-)epicatechin] enhances snail memory. J Exp Biol 215:3566–3576. https://doi.org/10.1242/jeb.070300
Haleagrahara N, Siew CJ, Mitra NK, Kumari M (2011) Neuroprotective effect of bioflavonoid quercetin in 6-hydroxydopamine-induced oxidative stress biomarkers in the rat striatum. Neurosci Lett 500:139–143. https://doi.org/10.1016/j.neulet.2011.06.021
Havsteen BH (2002) The biochemistry and medical significance of the flavonoids. Pharmacol Ther 96:67–202. https://doi.org/10.1016/s0163-7258(02)00298-x
Hawkins RD, Kandel ER, Bailey CH (2006) Molecular mechanisms of memory storage in Aplysia. Biol Bull 210:174–191. https://doi.org/10.2307/4134556
Hosokawa N, Hirayoshi K, Nakai A, Hosokawa Y, Marui N, Yoshida M, Sakai T, Nishino H, Aoike A, Kawai K, Nagata K (1990) Flavonoids inhibit the expression of Heat Shock Proteins. Cell Struct Funct 15:393–401. https://doi.org/10.1247/csf.15.393
Isabel G, Pascual A, Preat T (2004) Exclusive consolidated memory phases in Drosophila. Science 304:1024–1027. https://doi.org/10.1126/science.1094932
Itoh A, Komatsuzaki Y, Lukowiak K, Saito M (2021) Epicatechin increases the persistence of long-term memory formed by conditioned taste aversion in Lymnaea. J Exp Biol 4(Pt 3):jeb238055. https://doi.org/10.1242/jeb.238055
Jakubowicz-Gil J, Paduch R, Piersiak T, Głowniak K, Gawron A, Kandefer-Szerszeń M (2005) The effect of quercetin on pro-apoptotic activity of cisplatin in HeLa cells. Biochem Pharmacol 69:1343–1350. https://doi.org/10.1016/j.bcp.2005.01.022
Jayasena T, Poljak A, Smythe G, Braidy N, Münch G, Sachdev P (2013) The role of polyphenols in the modulation of sirtuins and other pathways involved in Alzheimer’s disease. Ageing Res Rev 12:867–883. https://doi.org/10.1016/j.arr.2013.06.003
Judge M, Quartermain D (1982) Characteristics of retrograde amnesia following reactivation of memory in mice. Physiol Behav 28:585–590. https://doi.org/10.1016/0031-9384(82)90034-8
Kagan D, Lukowiak K (2019) Configural learning in freshly collected, smart, wild Lymnaea. J Exp Biol 222(Pt 23):jeb212886. https://doi.org/10.1242/jeb.212886
Kandel ER, Dudai Y, Mayford MR (2014) The molecular and systems biology of memory. Cell 157:163–186. https://doi.org/10.1016/j.cell.2014.03.001
Karnik V, Braun M, Dalesman S, Lukowiak K (2012) Sensory input from the osphradium modulates the response to memory-enhancing stressors in Lymnaea stagnalis. J Exp Biol 215:536–542. https://doi.org/10.1242/jeb.061432
Khan H, Marya, Amin S, Kamal MA, Patel S (2018) Flavonoids as acetylcholinesterase inhibitors: Current therapeutic standing and future prospects. Biomed Pharmacother 101:860–870. https://doi.org/10.1016/j.biopha.2018.03.007
Kida S (2012) A functional role for CREB as a positive regulator of memory formation and LTP. Exp Neurobiol 21:136–140. https://doi.org/10.5607/en.2012.21.4.136
Kiss T, Pirger Z, Kemenes G (2009) Food-aversive classical conditioning increases a persistent sodium current in molluscan withdrawal interneurons in a transcription dependent manner. Neurobiol Learn Mem 2(1):114–9. doi: https://doi.org/10.1016/j.nlm.2009.03.001
Knezevic B, Dalesman S, Karnik V, Byzitter J, Lukowiak K (2011) Low external environmental calcium levels prevent forgetting in Lymnaea. J Exp Biol 214:2118–2124. https://doi.org/10.1242/jeb.054635
Knezevic B, Lukowiak K (2014) The flavonol epicatechin reverses the suppressive effects of a stressor on long-term memory formation. J Exp Biol 217:4004–4009. https://doi.org/10.1242/jeb.110726
Kong AN, Yu R, Chen C, Mandlekar S, Primiano T (2000) Signal transduction events elicited by natural products: Role of MAPK and caspase pathways in homeostatic response and induction of apoptosis. Arch Pharm Res 23:1–16. https://doi.org/10.1007/BF02976458
Letenneur L, Proust-Lima C, Le Gouge A, Dartigues JF, Barberger-Gateau P (2007) Flavonoid Intake and Cognitive Decline over a 10-Year Period. Am J Epidemiol 165:1364–1371. https://doi.org/10.1093/aje/kwm036
Lukowiak K (2000) Operant Conditioning in Lymnaea: Evidence for Intermediate- and Long-term Memory. Learn Mem 7:140–150. https://doi.org/10.1101/lm.7.3.140
Lukowiak K, Martens K, Orr M, Parvez K, Rosenegger D, Sangha S (2006) Modulation of aerial respiratory behaviour in a pond snail. Respir Physiol Neurobiol 154(1–2):61–72. https://doi.org/10.1016/j.resp.2006.02.009
Lukowiak K, Martens K, Rosenegger D, Browning K, de Caigny P, Orr M (2008) The perception of stress alters adaptive behaviours in Lymnaea stagnalis. J Exp Biol 211:1747–1756. https://doi.org/10.1242/jeb.014886
Lukowiak K, Ringseis E, Spencer G, Wildering W, Syed N (1996) Operant conditioning of aerial respiratory behaviour in Lymnaea stagnalis. J Exp Biol 199:683–691
Lukowiak K, Sunada H, Teskey M, Lukowiak K, Dalesman S (2014) Environmentally relevant stressors alter memory formation in the pond snail Lymnaea. J Exp Biol 217:76–83. https://doi.org/10.1242/jeb.089441
Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79:727–747. https://doi.org/10.1093/ajcn/79.5.727
Manach C, Williamson G, Morand C, Scalbert A, Rémésy C (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 81:230S–242S. https://doi.org/10.1093/ajcn/81.1.230S
Mandel S, Youdim MBH (2004) Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases. Free Radic Biol Med 37:304–317. https://doi.org/10.1016/j.freeradbiomed.2004.04.012
Manwell LA, Heikkila JJ (2007) Examination of KNK437- and quercetin-mediated inhibition of heat shock-induced heat shock protein gene expression in Xenopus laevis cultured cells. Comp Biochem Physiol A Mol Integr Physiol 148:521–530. https://doi.org/10.1016/j.cbpa.2007.06.422
Marra V, O’Shea M, Benjamin PR, Kemenes I (2013) Susceptibility of memory consolidation during lapses in recall. Nat Commun 4:1578. https://doi.org/10.1038/ncomms2591
Martens KR, De Caigny P, Parvez K, Amarell M, Wong C, Lukowiak K (2007) Stressful stimuli modulate memory formation in Lymnaea stagnalis. Neurobiol Learn Mem 87:391–403. https://doi.org/10.1016/j.nlm.2006.10.005
Mastroiacovo D, Kwik-Uribe C, Grassi D, Necozione S, Raffaele A, Pistacchio L, Righetti R, Bocale R, Lechiara MC, Marini C, Ferri C, Desideri G (2015) Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: the Cocoa, Cognition, and Aging (CoCoA) study—a randomized controlled trial. Am J Clin Nutr 101:538–548. https://doi.org/10.3945/ajcn.114.092189
Matsuno M, Horiuchi J, Yuasa Y, Ofusa K, Miyashita T, Masuda T, Saitoe M (2015) Long-term memory formation in Drosophila requires training-dependent glial transcription. J Neurosci 35:5557–5565. https://doi.org/10.1523/JNEUROSCI.3865-14.2015
McKenzie S, Eichenbaum H (2011) Consolidation and reconsolidation: Two lives of memories? Neuron 71:224–233. https://doi.org/10.1016/j.neuron.2011.06.037
Milekic MH, Alberini CM (2002) Temporally graded requirement for protein synthesis following memory reactivation. Neuron 36:521–525. https://doi.org/10.1016/S0896-6273(02)00976-5
Morel I, Lescoat G, Cogrel P, Sergent O, Pasdeloup N, Brissot P, Cillard P, Cillard J (1993) Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem Pharmacol 45:13–19. https://doi.org/10.1016/0006-2952(93)90371-3
Nader K, Einarsson E (2010) Memory reconsolidation: an update. Ann N Y Acad Sci 1191:27–41. https://doi.org/10.1111/j.1749-6632.2010.05443.x
Nader K, Schafe GE, Le Doux JE (2000) Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406:722–726. https://doi.org/10.1038/35021052
Nakagawa T, Itoh M, Ohta K, Hayashi Y, Hayakawa M, Yamada Y, Akanabe H, Chikaishi T, Nakagawa K, Itoh Y, Muro T, Yanagida D, Nakabayashi R, Mori T, Saito K, Ohzawa K, Suzuki C, Li S, Ueda M, Wang MX, Nishida E, Islam S, Tana, Kobori M, Inuzuka T (2016) Improvement of memory recall by quercetin in rodent contextual fear conditioning and human early-stage Alzheimer’s disease patients. NeuroReport 27:671–676. https://doi.org/10.1097/WNR.0000000000000594
Orr MV, Lukowiak K (2008) Electrophysiological and behavioral evidence demonstrating that predator detection alters adaptive behaviors in the snail Lymnaea. J Neurosci 28:2726–2734. https://doi.org/10.1523/JNEUROSCI.5132-07.2008
Parvez K (2005) Boosting intermediate-term into long-term memory. J Exp Biol 208:1525–1536. https://doi.org/10.1242/jeb.01545
Parvez K, Moisseev V, Lukowiak K (2006) A context-specific single contingent-reinforcing stimulus boosts intermediate-term memory into long-term memory. Eur J Neurosci 24:606–616. https://doi.org/10.1111/j.1460-9568.2006.04952.x
Philips GT, Tzvetkova EI, Marinesco S, Carew TJ (2006) Latent memory for sensitization in Aplysia. Learn Mem 13:224–229. https://doi.org/10.1101/lm.111506
Pirger Z, László Z, Kemenes I, Tóth G, Reglodi D, Kemenes G (2010) A homolog of the vertebrate pituitary adenylate cyclase-activating polypeptide is both necessary and instructive for the rapid formation of associative memory in an invertebrate. J Neurosci 30(41):13766–73. doi: https://doi.org/10.1523/JNEUROSCI.2577-10.2010
Rivi V, Batabyal A, Juego K, Kakadiya M, Benatti C, Blom JMC, Lukowiak K (2021a) To eat or not to eat: a Garcia effect in pond snails (Lymnaea stagnalis). J Comp Physiol A Neuroethol Sens Neural Behav Physiol 207(4):479–495. https://doi.org/10.1007/s00359-021-01491-5
Rivi V, Benatti C, Colliva C, Radighieri G, Brunello N, Tascedda F, Blom JMC (2020) Lymnaea stagnalis as model for translational neuroscience research: From pond to bench. Neurosci Biobehav Rev 108:602–616. https://doi.org/10.1016/j.neubiorev.2019.11.020
Rivi V, Benatti C, Lukowiak K, Colliva C, Alboni S, Tascedda F, Blom JMC (2021b) What can we teach Lymnaea and what can Lymnaea teach us? Biol Rev 96(4):1590–1602. https://doi.org/10.1111/brv.12716
Robak J, Gryglewski RJ (1988) Flavonoids are scavengers of superoxide anions. Biochem Pharmacol 37:837–841. https://doi.org/10.1016/0006-2952(88)90169-4
Rosenegger D (2004) Learning and memory in Lymnaea are negatively altered by acute low-level concentrations of hydrogen sulphide. J Exp Biol 207:2621–2630. https://doi.org/10.1242/jeb.01073
Rosenzweig MR, Bennett EL, Colombo PJ, Lee DW, Serrano PA (1993) Short-term, intermediate-term, and long-term memories. Behav Brain Res 57:193–198. https://doi.org/10.1016/0166-4328(93)90135-D
Sangha S (2003) Intermediate and long-term memories of associative learning are differentially affected by transcription versus translation blockers in Lymnaea. J Exp Biol 206:1605–1613. https://doi.org/10.1242/jeb.00301
Sangha S, Morrow R, Smyth K, Cooke R, Lukowiak K (2003) Cooling blocks ITM and LTM formation and preserves memory. Neurobiol Learn Mem 80:130–139. https://doi.org/10.1016/S1074-7427(03)00065-0
Sangha S, Scheibenstock A, Lukowiak K (2003b) Reconsolidation of a long-term memory in Lymnaea requires new protein and RNA synthesis and the soma of right pedal dorsal 1. J Neurosci 23:8034–8040. https://doi.org/10.1523/JNEUROSCI.23-22-08034.2003
Sara SJ (2000) Retrieval and reconsolidation: toward a neurobiology of remembering. Learn Mem 7:73–84. https://doi.org/10.1101/lm.7.2.73
Scheibenstock A, Krygier D, Haque Z, Syed N, Lukowiak K (2002) The soma of RPeD1 must be present for long-term memory formation of associative learning in Lymnaea. J Neurophysiol 88:1584–1591. https://doi.org/10.1152/jn.2002.88.4.1584
Schroeter H, Bahia P, Spencer JP, Sheppard O, Rattray M, Cadenas E, Rice-Evans C, Williams RJ (2007) (-)Epicatechin stimulates ERK-dependent cyclic AMP response element activity and up-regulates GluR2 in cortical neurons. J Neurochem 101:1596–1606. https://doi.org/10.1111/j.1471-4159.2006.04434.x
Silva AJ, Kogan JH, Frankland PW, Kida S (1998) CREB and memory. Annu Rev Neurosci 21:127–148. https://doi.org/10.1146/annurev.neuro.21.1.127
Socci V, Tempesta D, Desideri G, De Gennaro L, Ferrara M (2017) Enhancing human cognition with cocoa flavonoids. Front Nutr 4:19. https://doi.org/10.3389/fnut.2017.00019
Spencer JPE (2007) The interactions of flavonoids within neuronal signalling pathways. Genes Nutr 2:257–273. https://doi.org/10.1007/s12263-007-0056-z
Spencer GE, Syed NI, Lukowiak K (1999) Neural changes after operant conditioning of the aerial respiratory behavior in Lymnaea stagnalis. J Neurosci 19:1836–1843
Spencer GE, Kazmi MH, Syed NI, Lukowiak K (2002) Changes in the activity of a CPG neuron after the reinforcement of an operantly conditioned behavior in Lymnaea. J Neurophysiol 88:1915–1923. https://doi.org/10.1152/jn.2002.88.4.1915
Spencer JPE, Rice-Evans C, Williams RJ (2003) Modulation of pro-survival Akt/Protein Kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability. J Biol Chem 278:34783–34793. https://doi.org/10.1074/jbc.M305063200
Squire LR, Dede AJ (2015) Conscious and unconscious memory systems. Cold Spring Harb Perspect Biol 7(3):a021667. https://doi.org/10.1101/cshperspect.a021667
Stevens CF (1994) CREB and memory consolidation. Neuron 13:769–770. https://doi.org/10.1016/0896-6273(94)90244-5
Sunada H, Riaz H, de Freitas E, Lukowiak K, Swinton C, Swinton E, Protheroe A, Shymansky T, Komatsuzaki Y, Lukowiak K (2016) Heat stress enhances LTM formation in Lymnaea: role of HSPs and DNA methylation. J Exp Biol 219:1337–1345. https://doi.org/10.1242/jeb.134296
Sunada H, Totani Y, Nakamura R, Sakakibara M, Lukowiak K, Ito E (2017a) Two strains of Lymnaea stagnalis and the progeny from their mating display differential memory-forming ability on associative learning tasks. Front Behav Neurosci 11:11:161. https://doi.org/10.3389/fnbeh.2017.00161
Sunada H, Watanabe T, Hatakeyama D, Lee S, Forest J, Sakakibara M, Ito E, Lukowiak K (2017b) Pharmacological effects of cannabinoids on learning and memory in Lymnaea. J Exp Biol 220:3026–3038. https://doi.org/10.1242/jeb.159038
Suzuki A, Fukushima H, Mukawa T, Toyoda H, Wu LJ, Zhao MG, Xu H, Shang Y, Endoh K, Iwamoto T, Mamiya N, Okano E, Hasegawa S, Mercaldo V, Zhang Y, Maeda R, Ohta M, Josselyn SA, Zhuo M, Kida S (2011) Upregulation of CREB-mediated transcription enhances both short- and long-term memory. J Neurosci 31:8786–8802. https://doi.org/10.1523/JNEUROSCI.3257-10.2011
Swinton E, de Freitas E, Swinton C, Shymansky T, Hiles E, Zhang J, Rothwell C, Lukowiak K (2018) Green tea and cocoa enhance cognition in Lymnaea. Commun Integr Biol 11:e1434390. https://doi.org/10.1080/19420889.2018.1434390
Swinton C, Swinton E, Shymansky T, Hughes E, Zhang J, Rothwell C, Kakadiya M, Lukowiak K (2019) Configural learning: a higher form of learning in Lymnaea. J Exp Biol 4(Pt 3):jeb190405. https://doi.org/10.1242/jeb.190405
Syed NI, Bulloch AG, Lukowiak K (1992) The respiratory central pattern generator (CPG) of Lymnaea reconstructed in vitro. Acta Biol Hung 43:409–419
Tascedda F, Malagoli D, Accorsi A, Rigillo G, Blom JM, Ottaviani E (2015) Molluscs as models for translational medicine. Med Sci Monit Basic Res 21:96–99. https://doi.org/10.12659/MSMBR.894221
Teskey ML, Lukowiak KS, Riaz H, Dalesman S, Lukowiak K (2012) What’s hot: the enhancing effects of thermal stress on long-term memory formation in Lymnaea stagnalis. J Exp Biol 215:4322–4329. https://doi.org/10.1242/jeb.075960
Travica N, D’Cunha NM, Naumovski N, Kent K, Mellor DD, Firth J, Georgousopoulou EN, Dean OM, Loughman A, Jacka F, Marx WT (2009) Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies. Genes Nutr 4:227–242. https://doi.org/10.1007/s12263-009-0135-4
Tronson NC, Taylor JR (2007) Molecular mechanisms of memory reconsolidation. Nat Rev Neurosci 8:262–275. https://doi.org/10.1038/nrn2090
Tully T, Bourtchouladze R, Scott R, Tallman J (2003) Targeting the CREB pathway for memory enhancers. Nat Rev Drug Discov 2:267–277. https://doi.org/10.1038/nrd1061
Vauzour D, Vafeiadou K, Rice-Evans C, Williams RJ, Spencer JP (2007) Activation of pro-survival Akt and ERK1/2 signalling pathways underlie the anti-apoptotic effects of flavanones in cortical neurons. J Neurochem 103:1355–1367. https://doi.org/10.1111/j.1471-4159.2007.04841.x
Widmer YF, Bilican A, Bruggmann R, Sprecher SG (2018) Regulators of long-term memory revealed by mushroom body-specific gene expression profiling in Drosophila melanogaster. Genetics 209:1167–1181. https://doi.org/10.1534/genetics.118.301106
Williams RJ, Spencer JPE, Rice-Evans C (2004) Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med 36:838–849. https://doi.org/10.1016/j.freeradbiomed.2004.01.001
Yevchak AM, Loeb SJ, Fick DM (2008) Promoting cognitive health and vitality: a review of clinical implications. Geriatr Nurs 29:302–310. https://doi.org/10.1016/j.gerinurse.2007.10.017
Yin JC, Tully T (1996) CREB and the formation of long-term memory. Curr Opin Neurobiol 6:264–268. https://doi.org/10.1016/S0959-4388(96)80082-1
Zlotnik G, Vansintjan A (2019) Memory: an extended definition. Front Psychol 10:2523. https://doi.org/10.3389/fpsyg.2019.02523
Acknowledgements
We would like to thank Dr. Petra Hermann for providing us with the lab-reared population of snails. We would also like to thank Bevin Wiley, Diana Kagan, and David Chau for discussions in the lab. Finally, VR would thank the Italian Interuniversity Consortium of Biotechnology (CIB—Trieste, Italy) for providing a scholarship for carrying out training activities at foreign laboratories.
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Funding was provided by the Natural Sciences and Engineering Research Council of Canada (NSERC) to KL.
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VR, AB, and KL conceptualised and designed study. VR performed behavioural data collection, analysis and writing the first draft. AB, CB, JMCB, and FT critically revised manuscript. KL coordinated study, provided funding, and critically revised manuscript. All authors take responsibility of the data provided and consent to the publication of the manuscript.
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Rivi, V., Batabyal, A., Benatti, C. et al. A flavonoid, quercetin, is capable of enhancing long-term memory formation if encountered at different times in the learning, memory formation, and memory recall continuum. J Comp Physiol A 208, 253–265 (2022). https://doi.org/10.1007/s00359-021-01522-1
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DOI: https://doi.org/10.1007/s00359-021-01522-1