M. V. Accardi, H. Huang, and S. Authier, Seizure liability assessments using the hippocampal tissue slice: Comparison of non-clinical species, Journal of Pharmacological and Toxicological Methods, vol.93, pp.59-68, 2018.

P. Andersen, T. V. Bliss, and K. K. Skrede, Lamellar organization of hippocampal excitatory pathways, Experimental Brain Research, vol.13, issue.2, 1971.

E. L. Andrade, A. F. Bento, J. Cavalli, S. K. Oliveira, R. C. Schwanke et al.,

J. B. Calixto, Non-clinical studies in the process of new drug development -Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies, Brazilian Journal of Medical and Biological Research, vol.49, issue.12, 2016.

S. Authier, J. Arezzo, M. S. Delatte, M. Kallman, C. Markgraf et al., Safety pharmacology investigations on the nervous system: An industry survey, Journal of Pharmacological and Toxicological Methods, vol.81, pp.37-46, 2016.

M. Avoli, J. Louvel, I. Kurcewicz, R. Pumain, and M. Barbarosie, Extracellular free potassium and calcium during synchronous activity induced by 4-aminopyridine in the juvenile rat hippocampus, The Journal of Physiology, vol.493, issue.3, pp.707-717, 1996.

M. Avoli, M. D'antuono, J. Louvel, R. Köhling, G. Biagini et al.,

V. Tancredi, Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro, Progress in Neurobiology, vol.68, issue.3, pp.77-78, 2002.

M. Avoli and M. Curtis, GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity, Progress in Neurobiology, vol.95, issue.2, pp.104-132, 2011.

J. S. Bains, J. M. Longacher, and K. J. Staley, Reciprocal interactions between CA3 network activity and strength of recurrent collateral synapses, Nature Neuroscience, vol.2, issue.8, pp.720-726, 1999.

M. Bankstahl, J. P. Bankstahl, P. Bloms-funke, and W. Löscher, Striking differences in proconvulsant-induced alterations of seizure threshold in two rat models, NeuroToxicology, vol.33, issue.1, pp.127-137, 2012.

Y. Ben-ari and M. Gho, Long-lasting modification of the synaptic properties of rat CA3 hippocampal neurones induced by kainic acid, The Journal of Physiology, vol.404, issue.1, pp.365-384, 1988.

Y. Ben-ari and R. Cossart, Kainate, a double agent that generates seizures: Two decades of progress, Trends in Neurosciences, vol.23, issue.11, pp.1659-1662, 2000.
URL : https://hal.archives-ouvertes.fr/inserm-00485223

D. Bianchi, A. Marasco, A. Limongiello, C. Marchetti, H. Marie et al., On the mechanisms underlying the depolarization block in the spiking dynamics of CA1 pyramidal neurons, Journal of Computational Neuroscience, vol.33, issue.2, pp.207-225, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00854872

J. A. Bradley, H. H. Luithardt, M. R. Metea, and C. J. Strock, In vitro screening for seizure liability using microelectrode Array technology, Toxicological Sciences, vol.163, issue.1, pp.240-253, 2018.

P. J. Buckle and H. L. Haas, Enhancement of synaptic transmission by 4-aminopyridine in hippocampal slices of the rat, The Journal of Physiology, vol.326, issue.1, pp.109-122, 1982.


M. Cataldi, G. Panuccio, A. Cavaccini, M. D'antuono, M. Taglialatela et al., Involvement of inward rectifier and M-type currents in carbachol-induced epileptiform synchronization, Neuropharmacology, vol.60, issue.4, pp.653-661, 2011.

H. Chen, T. E. Albertson, and K. R. Olson, Treatment of drug-induced seizures, British Journal of Clinical Pharmacology, vol.81, issue.3, pp.412-419, 2016.

A. J. Chesi and T. W. Stone, Alkylxanthine adenosine antagonists and epileptiform activity in rat hippocampal slices in vitro, Experimental Brain Research, vol.113, issue.2, pp.303-310, 1997.

S. L. Cohen, B. J. Morley, and O. C. Snead, An EEG analysis of convulsive activity produced by cholinergic agents, Progress in Neuro-Psychopharmacology, vol.5, issue.4, pp.383-388, 1981.

A. Cole and R. Nicoll, Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells, Science, vol.221, issue.4617, pp.1299-1301, 1983.

A. E. Cole and R. A. Nicoll, The pharmacology of cholinergic excitatory responses in hippocampal pyramidal cells, Brain Research, vol.305, issue.2, pp.90434-90441, 1984.

L. V. Colom and P. Saggau, Spontaneous interictal-like activity originates in multiple areas of the CA2-CA3 region of hippocampal slices, Journal of Neurophysiology, vol.71, issue.4, pp.1574-1585, 1994.

J. W. Cruickshank, S. M. Brudzynski, and R. S. Mclachlan, Involvement of M1 muscarinic receptors in the initiation of cholinergically induced epileptic seizures in the rat brain, Brain Research, vol.643, issue.1-2, pp.90017-90022, 1994.

D. Debanne, S. M. Thompson, and B. H. Gahwiler, A brief period of Epileptiform activity strengthens excitatory synapses in the rat Hippocampus in vitro, Epilepsia, vol.47, issue.2, pp.247-256, 2006.

J. A. Dimasi, H. G. Grabowski, and R. W. Hansen, Innovation in the pharmaceutical industry: New estimates of R&D costs, Journal of Health Economics, vol.47, pp.20-33, 2016.

D. M. Durand, E. Park, and A. L. Jensen, Potassium diffusive coupling in neural networks, Philosophical Transactions of the Royal Society B: Biological Sciences, vol.365, pp.2347-2362, 1551.

N. Dürmüller, P. Guillaume, P. Lacroix, R. D. Porsolt, and P. Moser, The use of the dog electroencephalogram (EEG) in safety pharmacology to evaluate proconvulsant risk, Journal of Pharmacological and Toxicological Methods, vol.56, issue.2, pp.234-238, 2007.

A. Easter, T. H. Sharp, J. Valentin, and C. E. Pollard, Pharmacological validation of a semi-automated in vitro hippocampal brain slice assay for assessment of seizure liability, Journal of Pharmacological and Toxicological Methods, vol.56, issue.2, pp.223-233, 2007.

A. Easter, M. E. Bell, J. R. Damewood, W. S. Redfern, J. Valentin et al.,

R. A. Bialecki, Approaches to seizure risk assessment in preclinical drug discovery, Drug Discovery Today, vol.14, pp.876-884, 2009.

, Assessment of abuse potential of drugs guidance for industry, vol.37, 2017.

P. Federico and B. A. Macvicar, Imaging the induction and spread of seizure activity in the isolated brain of the Guinea pig: The roles of GABA and glutamate receptors, Journal of Neurophysiology, vol.76, issue.5, pp.3471-3492, 1996.

M. R. De-feo, O. Mecarelli, and G. F. Ricci, Bicuculline-and allylglycine-induced epilepsy in developing rats, Experimental Neurology, vol.90, issue.2, pp.411-421, 1985.

R. S. Fisher and B. E. Alger, Electrophysiological mechanisms of kainic acid-induced epileptiform activity in the rat hippocampal slice, The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, vol.4, issue.5, pp.1312-1323, 1984.

D. D. Fraser and B. A. Macvicar, Cholinergic-dependent plateau potential in hippocampal CA1 pyramidal neurons, The Journal of Neuroscience, vol.16, issue.13, pp.4113-4128, 1996.

R. C. Froemke, A. Gonzalez-sulser, J. Wang, G. K. Motamedi, M. Avoli et al., Temporal modulation of spike-timing-dependent plasticity. Frontiers in Synaptic Neuroscience, Neuropharmacology, vol.60, issue.7-8, pp.1142-1153, 2010.

J. Hamdam, S. Sethu, T. Smith, A. Alfirevic, M. Alhaidari et al., Safety pharmacology -Current and emerging concepts, Toxicology and Applied Pharmacology, vol.273, issue.2, pp.229-241, 2013.

M. Hasselmo and E. Schnell, Laminar selectivity of the cholinergic suppression of synaptic transmission in rat hippocampal region CA1: Computational modeling and brain slice physiology, The Journal of Neuroscience, vol.14, issue.6, pp.3898-3914, 1994.

S. Irwin, Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse, Psychopharmacologia, vol.13, issue.3, pp.222-257, 1968.

D. Johnston and T. H. Brown, Giant synaptic potential hypothesis for epileptiform activity, Science, issue.4479, pp.294-297, 1981.

K. I. Kaitin, Deconstructing the drug development process: The new face of innovation, Clinical Pharmacology & Therapeutics, vol.87, issue.3, pp.356-361, 2010.

Y. Kitano, C. Usui, K. Takasuna, M. Hirohashi, and M. Nomura, Increasingcurrent electroshock seizure test: A new method for assessment of anti-and proconvulsant activities of drugs in mice, Journal of Pharmacological and Toxicological Methods, vol.35, issue.1, pp.115-123, 1996.

T. Klausberger, GABAergic interneurons targeting dendrites of pyramidal cells in the CA1 area of the hippocampus, European Journal of Neuroscience, vol.30, issue.6, pp.947-957, 2009.

I. Kola and J. Landis, Can the pharmaceutical industry reduce attrition rates?, Nature reviews. Drug Discovery, vol.3, issue.8, pp.1474-1776, 2004.

G. J. Lees and M. Sandberg, Evoked field potential changes in the rat hippocampus produced by toxic doses of glutamate agonists and metabolic inhibitors: Correlation with subsequent neuronal death, Experimental Brain Research, vol.85, issue.3, 1991.

M. Lévesque and M. Avoli, The kainic acid model of temporal lobe epilepsy, Neuroscience & Biobehavioral Reviews, vol.37, issue.10, pp.2887-2899, 2013.

M. Lévesque, M. Cataldi, L. Chen, S. Hamidi, and M. Avoli, Carbachol-induced network oscillations in an in vitro limbic system brain slice, Neuroscience, vol.348, pp.153-164, 2017.

J. Lipski, M. C. Bellingham, M. J. West, and P. Pilowsky, Limitations of the technique of pressure microinjection of excitatory amino acids for evoking responses from localized regions of the CNS, Journal of Neuroscience Methods, vol.26, issue.2, pp.169-179, 1988.

W. Löscher, Preclinical assessment of proconvulsant drug activity and its relevance for predicting adverse events in humans, European Journal of Pharmacology, vol.610, issue.1-3, pp.1-11, 2009.

W. Löscher, D. Hönack, C. P. Fassbender, and B. Nolting, The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. III. Pentylenetetrazole seizure models, Epilepsy Research, vol.8, issue.3, pp.171-189, 1991.

W. Löscher and D. Schmidt, Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations, Epilepsy Research, vol.2, issue.3, p.90054, 1988.

E. W. Lothman, Seizure circuits in the hippocampus and associated structures, Hippocampus, vol.4, issue.3, pp.286-290, 1994.

H. D. Lux, U. Heinemann, and I. Dietzel, Ionic changes and alterations in the size of the extracellular space during epileptic activity, Advances in Neurology, vol.44, pp.619-639, 1986.

A. N. Mead, H. R. Amouzadeh, K. Chapman, L. Ewart, A. Giarola et al.,

H. M. Vargas, Assessing the predictive value of the rodent neurofunctional assessment for commonly reported adverse events in phase I clinical trials, Regulatory Toxicology and Pharmacology, vol.80, pp.348-357, 2016.

L. Menendez-de-la-prida, G. Huberfeld, I. Cohen, and R. Miles, Threshold behavior in the initiation of hippocampal population bursts, Neuron, vol.49, issue.1, pp.131-142, 2006.

J. Mitterdorfer and B. P. Bean, Potassium currents during the action potential of hippocampal CA3 neurons, The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, vol.22, issue.23, pp.10106-10115, 2002.

V. C. Moser, B. M. Cheek, and R. C. Macphail, A multidisciplinary approach to toxicological screening: III. Neurobehavioral toxicity, Journal of Toxicology and Environmental Health, vol.45, issue.2, pp.173-210, 1995.

A. R. Mcquiston, Cholinergic modulation of excitatory synaptic input integration in hippocampal CA1: Acetylcholine and excitatory synaptic integration in hippocampal CA1, The Journal of Physiology, vol.588, issue.19, pp.3727-3742, 2010.

P. Perreault and M. Avoli, Physiology and pharmacology of epileptiform activity induced by 4-aminopyridine in rat hippocampal slices, Journal of Neurophysiology, vol.65, issue.4, pp.771-785, 1991.

J. Pillai and M. R. Sperling, Interictal EEG and the diagnosis of epilepsy, Epilepsia, vol.47, issue.s1, pp.14-22, 2006.

S. Rama, M. Zbili, A. Fékété, M. Tapia, M. J. Benitez et al.,

D. Debanne, The role of axonal Kv1 channels in CA3 pyramidal cell excitability, Scientific Reports, vol.7, issue.1, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01766826

M. A. Rogawski, W. Löscher, and J. M. Rho, Mechanisms of action of antiseizure drugs and the ketogenic diet. Cold Spring Harbor Perspectives in Medicine, vol.6, 2016.

M. J. Rowan, L. Blum, and . Manzo, Central nervous system toxicity evaluation in vitro: neurophysiological approach. Neurotoxicolgy (Drug and Chemical Toxicology) (Marcel Dekker). 3. Neurotoxicolgy (Drug and Chemical Toxicology) (Marcel Dekker), pp.586-612, 1984.

P. A. Rutecki, F. J. Lebeda, and D. Johnston, 4-Aminopyridine produces epileptiform activity in hippocampus and enhances synaptic excitation and inhibition, Journal of Neurophysiology, vol.57, issue.6, pp.1911-1924, 1911.

P. A. Schwartzkroin, Role of the hippocampus in epilepsy, Hippocampus, vol.4, issue.3, pp.239-242, 1994.

A. Semyanov and O. Godukhin, Epileptiform activity and EPSP-spike potentiation induced in rat hippocampal CA1 slices by repeated high-K+: Involvement of ionotropic glutamate receptors and Ca2+/calmodulin-dependent protein kinase II, Neuropharmacology, vol.40, issue.2, pp.147-154, 2001.

A. Semyanov, E. Morenkov, A. Savin, and O. Godukhin, In vivo hippocampal kindling occludes the development of in vitro kindling-like state in CA1 area of rat hippocampal slices, Epilepsy Research, vol.38, issue.1, pp.76-81, 1999.

D. A. Spyker, C. Lynch, J. Shabanowitz, and J. A. Sinn, Poisoning with 4-aminopyridine: Report of three cases, Clinical Toxicology, vol.16, issue.4, pp.487-497, 1980.

K. J. Staley, A. White, and F. E. Dudek, Interictal spikes: Harbingers or causes of epilepsy?, Neuroscience Letters, vol.497, issue.3, pp.247-250, 2011.

J. W. Swann and C. M. Gomez-di-cesare, Developmental plasticity and hippocampal epileptogenesis, Hippocampus, vol.4, issue.3, pp.266-269, 1994.

V. Tancredi and M. Avoli, Control of spontaneous epileptiform discharges by extracellular potassium: An in vitro study in the CA1 subfield of the hippocampal slice, Experimental Brain Research, vol.67, issue.2, 1987.

R. A. Tasker, P. B. Bernard, T. A. Doucette, D. S. Kerr, Y. Zabidin et al., Comparison of the in vitro and in vivo neurotoxicity of three new sources of kainic acid, Amino Acids, vol.23, issue.1-3, pp.45-54, 2002.

S. Thesleff, Aminopyridines and synaptic transmission, Neuroscience, vol.5, issue.8, pp.1413-1419, 1980.

R. D. Traub and R. K. Wong, Penicillin-induced epileptiform activity in the hippocampal slice: A model of synchronization of CA3 pyramidal cell bursting, Neuroscience, vol.6, issue.2, pp.223-230, 1981.

R. D. Traub and J. G. Jefferys, Simulations of epileptiform activity in the hippocampal CA3 region in vitro, Hippocampus, vol.4, issue.3, pp.281-285, 1994.

M. Blum, L. Valentino, R. Dingledine, and R. , Presynaptic inhibitory effect of acetylcholine in the hippocampus, The Journal of Neuroscience, vol.1, issue.7, pp.784-792, 1981.

J. R. Vargas, D. K. Takahashi, K. E. Thomson, and K. S. Wilcox, The Expression of Kainate Receptor Subunits in Hippocampal Astrocytes After Experimentally Induced Status Epilepticus, Journal of Neuropathology & Experimental Neurology, vol.72, issue.10, pp.919-932, 2013.

J. H. Williams and J. A. Kauer, Properties of carbachol-induced oscillatory activity in rat hippocampus, Journal of Neurophysiology, vol.78, issue.5, pp.2631-2640, 1997.

M. J. Winter, W. S. Redfern, A. J. Hayfield, S. F. Owen, J. Valentin et al., Validation of a larval zebrafish locomotor assay for assessing the seizure liability of early-stage development drugs, Journal of Pharmacological and Toxicological Methods, vol.57, issue.3, pp.176-187, 2008.

H. Zhang, W. Li, Y. Xie, W. Wang, L. Li et al., Rapid and accurate assessment of seizure liability of drugs by using an optimal support vector machine method, Toxicology In Vitro, vol.25, issue.8, pp.1848-1854, 2011.

E. Steidl, Journal of Pharmacological and Toxicological Methods, vol.99, p.106587, 2019.