{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:41:20Z","timestamp":1760060480212,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CIHR Project"},{"name":"NSERC DG"},{"name":"Digital Research Alliance of Canada"},{"name":"Alberta Graduate Excellence Scholarship"},{"name":"Alberta Innovates Summer Research Studentship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epilepsy affects 50 to 70 million people worldwide and is characterized by recurring seizures that accelerate neurodegeneration; however, its mechanisms are still not well understood. It was proposed that epileptogenesis may be \u201chijacking\u201d the mechanisms underlying normal memory formation, where synapses involved in seizure activity are strengthened after each seizure, similarly to the strengthening of memories during the consolidation processes. To investigate this link, we used a kindling model of temporal lobe epilepsy in mice and tested whether disrupting memory consolidation could alter epileptogenesis. Animals were kindled until stage 3 behavioral seizures on the Racine scale were reached. In subsequent sessions, rapamycin was administered within 10 min following kindling to inhibit protein synthesis essential for memory consolidation in the neurons involved in a seizure. Rapamycin reduced the freezing response to sensory stimuli preceding a seizure, suggesting that memory consolidation was disrupted; however, epileptogenesis was not affected. Additionally, we tested whether administering isoflurane, which reduces neuronal activity, could weaken seizure-associated patterns by interfering with memory reconsolidation processes. This intervention also did not reduce the intensity of seizures. Altogether, these preliminary results appear to be inconsistent with the hypothesis that epileptogenesis involves the same mechanisms as memory formation processes.<\/jats:p>","DOI":"10.3390\/ijms26178364","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T08:01:01Z","timestamp":1756454461000},"page":"8364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intermediate Stage of Epileptogenesis Is Not Affected by Disrupting Memory Consolidation Processes"],"prefix":"10.3390","volume":"26","author":[{"given":"Carlos","family":"Howey","sequence":"first","affiliation":[{"name":"Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Autumn","family":"McFetridge","sequence":"additional","affiliation":[{"name":"Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4929-5781","authenticated-orcid":false,"given":"Artur","family":"Luczak","sequence":"additional","affiliation":[{"name":"Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"\u0141ukasiuk, K., and Laso\u0144, W. (2023). Emerging molecular targets for anti-epileptogenic and epilepsy modifying drugs. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032928"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.neuron.2009.05.015","article-title":"Neurons that fire together also conspire together:Is normal sleep circuitry hijacked to generate epilepsy?","volume":"62","author":"Beenhakker","year":"2009","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3934\/Neuroscience.2022007","article-title":"Epileptic seizures and link to memory processes","volume":"9","author":"Das","year":"2022","journal-title":"AIMS Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2966","DOI":"10.1093\/brain\/awae159","article-title":"High frequency oscillations in human memory and cognition: A neurophysiological substrate of engrams?","volume":"147","author":"Kucewicz","year":"2024","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e2302676120","DOI":"10.1073\/pnas.2302676120","article-title":"Interictal epileptiform discharges affect memory in an Alzheimer\u2019s disease mouse model","volume":"120","author":"Soula","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Squire, L.R., Genzel, L., Wixted, J.T., and Morris, R.G. (2015). Memory consolidation. Cold Spring Harb. Perspect. Biol., 7.","DOI":"10.1101\/cshperspect.a021766"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Farrell, J.S., Wolff, M.D., and Teskey, G.C. (2017). Neurodegeneration and pathology in epilepsy: Clinical and basic perspectives. Neurodegenerative Diseases: Pathology, Mechanisms, and Potential Therapeutic Targets, Springer Nature.","DOI":"10.1007\/978-3-319-57193-5_12"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Al-Redouan, A., Busch, A., Salaj, M., Kubova, H., and Druga, R. (2025). Dorsal Striatum Is Compromised by Status Epilepticus Induced in Immature Developing Animal Experimental Model of Mesial Temporal Lobe Epilepsy. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073349"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Aniol, V.A., Lazareva, N.A., Moiseeva, Y.V., Nedogreeva, O.A., Novikova, M.R., Kostryukov, P.A., Onufriev, M.V., and Gulyaeva, N.V. (2025). Effects of Phenosanic Acid in Rat Seizure Models. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125668"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.neures.2021.08.001","article-title":"Molecular mechanism of hippocampal long-term potentiation\u2013Towards multiscale understanding of learning and memory","volume":"175","author":"Hayashi","year":"2022","journal-title":"Neurosci. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.yebeh.2016.05.025","article-title":"Spontaneous ripples in the hippocampus correlate with epileptogenicity and not memory function in patients with refractory epilepsy","volume":"62","author":"Jacobs","year":"2016","journal-title":"Epilepsy Behav."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1523\/JNEUROSCI.3019-14.2015","article-title":"Evidence for consolidation of neuronal assemblies after seizures in humans","volume":"35","author":"Bower","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1016\/j.clinph.2014.12.003","article-title":"Sleep affects cortical source modularity in temporal lobe epilepsy: A high-density EEG study","volume":"126","author":"Storti","year":"2015","journal-title":"Clin. Neurophysiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1093\/brain\/awx179","article-title":"Involvement of fast-spiking cells in ictal sequences during spontaneous seizures in rats with chronic temporal lobe epilepsy","volume":"140","author":"Neumann","year":"2017","journal-title":"Brain"},{"key":"ref_15","first-page":"395","article-title":"Effect of low-frequency repetitive transcranial magnetic stimulation on cognitive function in rats with medial temporal lobe epilepsy","volume":"83","author":"Che","year":"2023","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1007\/s00018-019-03180-8","article-title":"MMPs in learning and memory and neuropsychiatric disorders","volume":"76","author":"Beroun","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Liguz-Lecznar, M., Dobrzanski, G., and Kossut, M. (2022). Somatostatin and somatostatin-containing interneurons\u2014From plasticity to pathology. Biomolecules, 12.","DOI":"10.1038\/s41598-022-22801-0"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.nlm.2007.12.004","article-title":"Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation","volume":"90","author":"Blundell","year":"2008","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Teskey, G. (2020). Kindling. Oxford Research Encyclopedia of Psychology, Oxford University Press.","DOI":"10.1093\/acrefore\/9780190236557.013.790"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.nlm.2013.08.014","article-title":"Systemic inhibition of mTOR kinase via rapamycin disrupts consolidation and reconsolidation of auditory fear memory","volume":"112","author":"Hebert","year":"2014","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12977","DOI":"10.1523\/JNEUROSCI.4209-06.2006","article-title":"Translational control via the mammalian target of rapamycin pathway is critical for the formation and stability of long-term fear memory in amygdala neurons","volume":"26","author":"Parsons","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhang, F., Huang, S., Bu, H., Zhou, Y., Chen, L., Kang, Z., Chen, L., Yan, H., Yang, C., and Yan, J. (2021). Disrupting reconsolidation by systemic inhibition of mTOR kinase via rapamycin reduces cocaine seeking behavior. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.652865"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1017\/S0317167100020539","article-title":"Does the engram of kindling model the engram of normal long term memory?","volume":"2","author":"Goddard","year":"1975","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/nm.4084","article-title":"Interictal epileptiform discharges induce hippocampal\u2013cortical coupling in temporal lobe epilepsy","volume":"22","author":"Gelinas","year":"2016","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1002\/ana.25744","article-title":"Hippocampal interictal spikes during sleep impact long-term memory consolidation","volume":"87","author":"Lambert","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_26","unstructured":"Sen, C.K. (2015). Chapter 29\u2014MicroRNA Regulation of mTOR Function. MicroRNA in Regenerative Medicine, Academic Press."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.bbapap.2007.08.015","article-title":"Role of mTOR in physiology and pathology of the nervous system","volume":"1784","author":"Swiech","year":"2008","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.cmet.2014.01.001","article-title":"Rapamycin: One drug, many effects","volume":"19","author":"Li","year":"2014","journal-title":"Cell Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2995","DOI":"10.1002\/brb3.2995","article-title":"Advances in the mTOR signaling pathway and its inhibitor rapamycin in epilepsy","volume":"13","author":"Zhao","year":"2023","journal-title":"Brain Behav."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"107817","DOI":"10.1016\/j.neuropharm.2019.107817","article-title":"Selective inhibition of mTORC1\/2 or PI3K\/mTORC1\/2 signaling does not prevent or modify epilepsy in the intrahippocampal kainate mouse model","volume":"162","author":"Gericke","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/0014-4886(80)90097-7","article-title":"Effects of protein synthesis inhibition on kindling in the mouse","volume":"68","author":"Cain","year":"1980","journal-title":"Exp. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/0014-4886(79)90199-7","article-title":"Effect of inhibitors of protein synthesis on the development of kindled seizures in rats","volume":"66","author":"Jonec","year":"1979","journal-title":"Exp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1016\/S0140-6736(16)31419-2","article-title":"Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): A phase 3, randomised, double-blind, placebo-controlled study","volume":"388","author":"French","year":"2016","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/j.1476-5381.1994.tb13166.x","article-title":"Stereoselective and non-stereoselective actions of isoflurane on the GABAA receptor","volume":"112","author":"Hall","year":"1994","journal-title":"Br. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/ana.24804","article-title":"Isoflurane prevents acquired epilepsy in rat models of temporal lobe epilepsy","volume":"80","author":"Klee","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_36","first-page":"157","article-title":"Opioidergic and nitrergic systems mediate the anticonvulsant effect of mefloquine and chloroquine on seizures induced by pentylenetetrazol and maximal electroshock in mice","volume":"82","author":"Boroujeni","year":"2022","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ishii, T., Kaya, M., and Muroi, Y. (2024). Oral Administration of Probiotic Bifidobacterium breve Ameliorates Tonic\u2013Clonic Seizure in a Pentylenetetrazole-Induced Kindling Mouse Model via Integrin-Linked Kinase Signaling. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179259"},{"key":"ref_38","first-page":"e3282","article-title":"Recording large-scale neuronal ensembles with silicon probes in the anesthetized rat","volume":"56","author":"Schjetnan","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1126\/science.8036517","article-title":"Reactivation of hippocampal ensemble memories during sleep","volume":"265","author":"Wilson","year":"1994","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.bbr.2013.07.022","article-title":"Beyond the silence: Bilateral somatosensory stimulation enhances skilled movement quality and neural density in intact behaving rats","volume":"253","author":"Faraji","year":"2013","journal-title":"Behav. Brain Res."},{"key":"ref_41","first-page":"135","article-title":"Measuring neuronal branching patterns using model-based approach","volume":"4","author":"Luczak","year":"2010","journal-title":"Front. Comput. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ryait, H., Bermudez-Contreras, E., Harvey, M., Faraji, J., Mirza Agha, B., Gomez-Palacio Schjetnan, A., Gruber, A., Doan, J., Mohajerani, M., and Metz, G.A.S. (2019). Data-driven analyses of motor impairments in animal models of neurological disorders. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000516"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Torabi, R., Jenkins, S., Harker, A., Whishaw, I.Q., Gibb, R., and Luczak, A. (2021). A neural network reveals motoric effects of maternal preconception exposure to nicotine on rat pup behavior: A new approach for movement disorders diagnosis. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.686767"},{"key":"ref_44","unstructured":"Tanabe, S., Eckert, M., Whishaw, I., Tatsuno, M., and Luczak, A. (2024). Using Generative and Explainable Neural Networks to Investigate the Relationship Between Motor Cortex Activity and Animal Behavior During Motor Task Learning. Res. Sq."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/0013-4694(72)90177-0","article-title":"Modification of seizure activity by electrical stimulation: II. Motor seizure","volume":"32","author":"Racine","year":"1972","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1159\/000528985","article-title":"Why is rapamycin not a rapalog?","volume":"69","author":"Kuerec","year":"2023","journal-title":"Gerontology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1111\/epi.13345","article-title":"Effects of rapamycin and curcumin treatment on the development of epilepsy after electrically induced status epilepticus in rats","volume":"57","author":"Drion","year":"2016","journal-title":"Epilepsia"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Das, R., Howey, C., McFetridge, A., Lapointe, V., and Luczak, A. (2024). Associating sensory cues with incoming seizures: Developing an animal model of auras. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-71885-3"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0014-4886(69)90128-9","article-title":"A permanent change in brain function resulting from daily electrical stimulation","volume":"25","author":"Goddard","year":"1969","journal-title":"Exp. Neurol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8364\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:34:32Z","timestamp":1760034872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,28]]},"references-count":49,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178364"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178364","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,8,28]]}}}