Overview

The hippocampus is a limbic structure that plays a critical role in the formation, consolidation and recall of various forms of memory, including episodic and spatial memory. How do such complex cognitive functions emerge from the activity of hippocampal neurons? One key property of the hippocampal network that has gained tremendous interest in recent years is its ability to encode and reactivate sequential activity patterns: specific subgroups of neurons become successively active, either in response to the ongoing behavioral and cognitive context, or spontaneously during recall, decision making and sleep. In the spatial domain, fast sequential activation of hippocampal ‘place cells’ anticipates future trajectories, associates traveled paths with rewarding or aversive stimuli, and appears to underlie certain forms of spatial learning. During subsequent sleep, reactivation of the same sequences plays a critical role in memory consolidation via a hippocampo-cortical dialogue. This versatile capacity to manipulate and memorize abstract information in the form of neural sequences may provide a unifying conceptual framework to reconcile the numerous functions of the hippocampus.

The goal of our research is to decipher the various roles of hippocampal dynamics, including their interactions with cortical and subcortical activity (in e.g. prefrontal cortex, medial and lateral entorhinal cortices, ventral and dorsal striatum, locus cœruleus, ventral tegmental area, etc.), and dissect their network mechanisms in freely moving rodents. We combine several cutting-edge technologies, including massively parallel electrophysiology across multiple brain areas, an innovative optical imaging approach, and optogenetics. We perform state-of-the-art electrophysiological recordings and are developing optical imaging and targeting approaches for real-time optical excitation or inhibition of single, identified neurons, as well as long-term monitoring of vast neural populations — all in freely moving rodents performing complex behavioral tasks in large scale mazes and sleeping. Advanced analytical and statistical methods allow us to unravel the mechanisms and roles of hippocampal sequences in the formation, consolidation and recall of memory.

Our team includes researchers with backgrounds in neurophysiology, animal behavior, physics and engineering. We are part of the Center for Interdisciplinary Research in Biology at the Collège de France, located in the historical center of Paris.

Michaël Zugaro

Formation and Consolidation of Episodic-Like Memory Traces

The ‘two-stage’ theory of memory posits that memory consolidation involves a dialogue during sleep between the hippocampus, where memory traces are initially formed, and the neocortex, where they are stored for long term retention. A prominent target is the medial prefrontal cortex, which over days becomes progressively involved in memory recall, concomitantly with a gradual hippocampal disengagement. During sleep, task-related neural activity patterns are replayed in both structures, orchestrated by various brain oscillations related to memory consolidation, that are often observed in temporal proximity.
 We have shown that fast sequential activation of hippocampal assemblies at the theta time scale (‘theta sequences’) are crucial to encode new memories, which are later replayed during sleep for memory consolidation (‘sleep replay’). We further demonstrated that the formation of these sequences requires fine timescale coordination between hippocampal cell assemblies. We have also shown that subsequent replay during sleep ripples is instrumental for memory consolidation, a long-standing hypothesis that had never received experimental confirmation. Our subsequent work established that hippocampal replay underlies a hippocampo-cortical dialogue, involving enhanced coupling between ripples, cortical delta waves and spindles. More recently, we have shown that, contrary to a generally accepted tenet in systems neuroscience, an ever-changing minority of cortical neurons remain active during delta waves, forming assemblies between neurons involved in coding memories. Delta waves thus shut most of the cortical network off to isolate critical computations involved in memory consolidation.
  1. Research Director (CNRS)
  2. Team Leader (Collège de France)
  3. Researcher (CNRS)
  4. Post-doctoral fellow in G. Buzsáki’s laboratory
  5. PhD in Neuroscience (Advisors: S. Wiener and A. Berthoz)
  6. Engineer in Mathematics and Computer Science (Compiègne University of Technology)

Selected Publications

  1. Oberto V*, Boucly C*, Gao HY*, Todorova R, Zugaro M, Wiener SI. Distributed cell assemblies spanning prefrontal cortex and striatum. Current Biology (accepted).
  2. R. Todorova, M. Zugaro. Isolated cortical computations during delta waves support memory consolidation. Science 366(6463):377-81.
  3. C. Drieu, R. Todorova, M. Zugaro. Nested sequences of hippocampal assemblies during behavior support subsequent sleep replay. Science 362(6415):675-679.
  4. N. Maingret, G. Girardeau, R. Todorova, M. Goutierre, M. Zugaro. Hippocampo-cortical coupling mediates memory consolidation during sleep. Nature Neuroscience 19(7):959-64. Highly Cited (top 1%)
  5. A. Cei, G. Girardeau, C. Drieu, K. El Kanbi, M. Zugaro. Reversed theta sequences of hippocampal cellassemblies during backward travel. Nature Neuroscience 17(5):719–24.
  6. G. Girardeau, A. Cei, M. Zugaro. Learning-induced plasticity regulates hippocampal sharp wave-ripple drive. The Journal of Neuroscience 34(15):5176–83.
  7. G. Girardeau, K. Benchenane, S.I. Wiener, G. Buzsáki, M. Zugaro. Selective suppression of hippocampal ripples impairs spatial memory. Nature Neuroscience 10:1222–3. Highly Cited (top 1%)

Other Publications

  1. C. Drieu, M. Zugaro. Hippocampal sequences during exploration: Mechanisms and functions. Front. Cell. Neurosci. doi: 10.3389/fncel.2019.00232 (Review).
  2. R. Todorova, M. Zugaro. Hippocampal ripples as a mode of communication with cortical and subcortical areas. Hippocampus doi: 10.1002/hipo.22997 (Review).
  3. J. Catanese, A. Viggiano, E. Cerasti, M. Zugaro, and S.I. Wiener. Retrospectively and prospectively modulated hippocampal place responses are differentially distributed along a common path in a continuous T-maze. The Journal of Neuroscience 34(39):13163–9.
  4. A. Arleo, C. Déjean, P. Allegraud, M. Khamassi, M. Zugaro, S.I. Wiener. Optic flow stimuli update anterodorsal thalamus head direction neuronal activity in rats. The Journal of Neuroscience 33(42):16790–5.
  5. J. Catanese, E. Cerasti, M. Zugaro, A. Viggiano, S.I. Wiener. Dynamics of decision-related activity in hippocampus. Hippocampus 22(9):1901–11.
  6. G. Girardeau, M. Zugaro. Hippocampal ripples and memory consolidation. Current Opinion in Neurobiology. 21(3):452–9 (Review).
  7. S. Herwik, S. Kisban, A.A.A. Aarts, K. Seidl, G. Girardeau, K. Benchenane, M. Zugaro, S.I. Wiener, O. Paul, H.P. Neves, P. Ruther. Fabrication technology for silicon-based microprobe arrays used in acute and sub-chronic neural recording. Journal of Micromechanics and Microengineering 19:074008.
  8. A. Sirota, S. Montgomery, S. Fujisawa, Y. Isomura, M. Zugaro, G. Buzsáki. Entrainment of neocortical neurons and gamma oscillations by the hippocampal theta rhythm. Neuron 60(4):683–97.
  9. C. Geisler, D. Robbe, M. Zugaro, A. Sirota, G. Buzsáki. Hippocampal place cell assemblies are speed-controlled oscillators. PNAS 104(19):8149–54.
  10. L. Hazan* & M. Zugaro* (equal contributions), G. Buzsáki. Klusters, NeuroScope, NDManager: a free software suite for neurophysiological data processing and visualization. Journal of Neuroscience Methods 155(2):207–16.
  11. M. Zugaro, L. Monconduit, G. Buzsáki. Spike phase precession persists after transient intrahippocampal perturbation. Nature Neuroscience 8:67–71.
  12. J. P. Bassett, M. Zugaro, G.M. Muir, E.J. Golob, R.U. Muller, J.S. Taube. Passive movements of the head do not abolish anticipatory firing properties of head direction cells. Journal of Neurophysiology 93(3):1304–16.
  13. M. Zugaro, A. Arleo, C. Dejean, E. Burguiere, M. Khamassi, S.I. Wiener. Rat anterodorsal thalamic head direction neurons depend upon dynamic visual signals to select anchoring landmark cues. European Journal of Neuroscience 20:530–6.
  14. P. Barthó, H. Hirase, L. Monconduit, M. Zugaro, K.D. Harris, G. Buzsáki. Characterization of neocortical principal cells and interneurons by network interactions and extracellular features. Journal of Neurophysiology 92:600–8.
  15. M. Zugaro, A. Arleo, A. Berthoz, S.I. Wiener. Rapid spatial reorientation and head direction cells, The Journal of Neuroscience, 23(8):3478–82.
  16. M. Zugaro, A. Berthoz, S.I. Wiener. Peak firing rates of rat anterodorsal thalamic head direction cells are higher during faster passive rotations, Hippocampus 12(4):481–6.
  17. S.I. Wiener and M. Zugaro, Multisensory processing for the elaboration of place and head direction responses in the limbic system, Cognitive Brain Research 14(1):75–90.
  18. M. Zugaro, E. Tabuchi, C.F. Fouquier, A. Berthoz, S.I. Wiener. Active locomotion increases peak firing rates of anterodorsal thalamic head direction cells, Journal of Neurophysiology 86(2):692–702.
  19. M. Zugaro, A. Berthoz, S.I. Wiener. Background, but not foreground, spatial cues are taken as references for head direction responses by rat anterodorsal thalamus neurons, The Journal of Neuroscience 21(RC154):1–5.
  20. M. Zugaro, E. Tabuchi, S.I. Wiener. Influence of conflicting visual, inertial and substratal cues on head direction cell activity, Experimental Brain Research 133:198–208.
  21. S.V. Albertin, A.B. Mulder, E. Tabuchi, M. Zugaro, S.I. Wiener. Lesions of the medial shell of the nucleus accumbens impair rats in finding larger rewards, but spare reward-seeking behavior, Behavioral Brain Research 117(1–2):173–83.

Sidney Wiener

Navigation and Spatial Memory

 Our focus is on cognitive functions such as spatial navigation learning, memory and decision-making and how they are linked with neuro-electrical activity, ensembles of neurons and neural networks. With chronically implanted multiple electrodes, we record from rats as they perform tasks requiring specific types of cognitive processing. Much of the work is centered on a popular experimental model for abstract representations in the brain – the place and head direction cells in the hippocampal system and related areas. We have studied how self-movement cues are engaged for this activity and also how brain areas downstream from the hippocampus (ventral striatum, prefrontal cortex) exploit this for navigation, orienting behavior and spatial memory. The role of sleep and associated brain oscillations in off-line memory consolidation is another focus. Furthermore coherence between oscillatory local field potentials in multiple structures is studied as a potential mechanism of selection of active pathways within the massively interconnected brain. This work is carried out in collaboration with roboticians and computational modelers to facilitate creation of bio-inspired automatons.
  1. Habilitation Degree (required in Europe to be qualified to train doctoral students), Pierre and Marie Curie University (Paris VI), Paris, France
  2. Ph.D. Neurosciences and Biophysics, Michigan State University, East Lansing, MI
  3. M.S. Biophysics, Michigan State University, East Lansing, MI

Currently also Scientific Officer for International Relations, Biological Sciences Institute, CNRS

  1. Oberto V*, Boucly C*, Gao HY*, Todorova R, Zugaro M, Wiener SI. Distributed cell assemblies spanning prefrontal cortex and striatum. Current Biology (accepted).
  2. Banquet JP, Gaussier P, Cuperlier N, Hok V, Save E, Poucet B, Quoy M, Wiener SI. Time as the fourth dimension in the hippocampus. Progress in Neurobiology , 101920 doi:10.1016/j.pneurobio.2020.101920.
  3. Wiener-Vacher SR, Wiener SI, Ajrezo L, Obeid R, Mohamed D, Boizeau P, Alberti C and Bucci MP. Dizziness and Convergence Insufficiency in Children: Screening and Management. Front. Integr. Neurosci. 13:25. doi: 10.3389/fnint.2019.00025.
  4. Xiang L, Harel A, Gao HG, Pickering AE, Sara SJ, Wiener SI. Behavioral correlates of activity of optogenetically identified locus coeruleus noradrenergic neurons in rats performing t-maze tasks. Scientific Reports 9:1361.
  5. Wiener-Vacher SR, Wiener SI. Video head impulse tests with a remote camera system: normative values of semicircular canal vestibulo-ocular reflex gain in infants and children. Front. Neurol. 8:434.
  6. Albertin SV, Wiener SI. Neuronal activity in the nucleus accumbens and hippocampus in rats during formation of seeking behavior in a radial maze. Bull Exp Biol Med. 158(4):405–9.
  7. Catanese J, Viggiano A, Cerasti E, Zugaro MB, Wiener SI Retrospectively and prospectively modulated hippocampal place responses are differentially distributed along a common path in a continuous T-maze. J. Neurosci. 34(39):13163–9.
  8. Arleo A, Déjean C, Allegraud P, Khamassi M, Zugaro M, Wiener SI Optic flow stimuli update anterodorsal thalamus head direction neuronal activity in rats. J. Neuroscience 33(42):16790–5.
  9. Wiener-Vacher SR, Hamilton DA, Wiener SI Vestibular activity and cognitive development in children: Perspectives. Frontiers Integrative Neuroscience 7:92.
  10. Catanese J, Cerasti E, Zugaro M, Viggiano A, Wiener SI Dynamics of decision-related activity in prospective hippocampal place cells. Hippocampus 22(9):1901–11
  11. Battaglia FP, Benchenane K, Sirota A, Pennartz CM, Wiener SI The hippocampus: Hub of brain network communication for memory. Trends Cogn Sci 15:310–318.
  12. Benchenane K, Peyrache A, Khamassi M, Tierney P, Gioanni Y, Battaglia FP, Wiener SI. Coherent theta oscillations and reorganization of spike timing in the hippocampal-prefrontal network upon learning. Neuron 66(6):921–36.
  13. Peyrache A, Benchenane K, Khamassi M, Wiener SI, Battaglia FP Sequential reinstatement of neocortical activity during slow oscillations depends on cells’ global activity. Front Sys. Neurosci. 3:18.
  14. Girardeau G, Benchenane K, Wiener SI, Buzsáki G, Zugaro MB Selective suppression of hippocampal ripples impairs spatial memory. Nature Neurosci. 12(10):1222–23
  15. Herwik S, Kisban S, Aarts AAA, Seidl K, Girardeau G, Benchenane K, Zugaro MB, Wiener SI, Paul O, Neves HP, Ruther P Fabrication technology for silicon-based microprobe arrays used in acute and sub-chronic neural recording. J. Micromech. Microeng. 19 074008 (11pp)
  16. Peyrache A, Khamassi M, Benchenane K, Wiener SI, Battaglia FP Replay of rule-learning related neural patterns in the prefrontal cortex during sleep. Nature Neurosci. 12(7):919–926
  17. Peyrache A, Benchenane K, Khamassi M, Wiener SI, Battaglia FP Principal component analysis on ensemble recordings reveal cell assemblies at high temporal resolution. J. Comput. Neurosci. DOI 10.1007/s10827–009-0154–6
  18. Khamassi M, Mulder AB, Tabuchi E, Douchamps V, Wiener SI Anticipatory reward signals in ventral striatal neurons of behaving rats. Eur. J. Neurosci., 28(9): 1849–1866
  19. Mulder A.B., Shibata R., Trullier O., Wiener S.I. Spatially selective reward site responses in tonically active neurons of the nucleus accumbens in behaving rats. Exp. Brain Res. 163:32–43.
  20. Zugaro M.B., Arleo A., Déjean C, Burguière E, Khamassi M, Wiener S.I. Rat anterodorsal thalamic head direction neurons depend upon dynamic visual signals to select anchoring landmark cues. Eur. J. Neurosci. 20:530–536
  21. Mulder AB, Tabuchi E, Wiener S.I. Neurons in hippocampal afferent zones of rat striatum parse routes into multi-pace segments during maze navigation Eur. J. Neurosci. 19:1923–1932
  22. Degris T, Sigaud O, Wiener SI., Arleo A Rapid response of head direction cells to reorienting visual cues: A computational model. Neurocomputing. 58–60C: 675–682
  23. Wiener S.I., Arleo A. Persistent activity in limbic system neurons: Neurophysiological and modeling perspectives. J. Physiol. (Paris) 97:547–555
  24. Zugaro M.B., Arleo A., Berthoz A., Wiener S.I. Rapid spatial reorientation and head direction cells. J. Neurosci. 23:3478–3482
  25. Tabuchi E., Mulder A.B., Wiener S.I. Reward value invariant place responses and reward site associated activity in hippocampal neurons of behaving rats. Hippocampus 13: 17–132
  26. Albertin SV, Mulder AB, Wiener SI. The advantages of electrophysiological control for the localization and selective lesioning of the nucleus accumbens in rats. Neurosci. Behav. Physiol. 33(8): 805–9
  27. Zugaro, M.B., Berthoz, A., Wiener S.I. Peak firing rates of rat anterodorsal thalamic head direction cells are higher during faster passive rotations. Hippocampus 12:481–486.
  28. Wiener, S.I., Zugaro, M.B. Multisensory processing for the elaboration of place and head direction responses in the limbic system. Cognitive Brain Research 14:75–90.
  29. Albertin, S.V., Mulder, A.B., Wiener, S.I. [Electrophysiological control in localization and selective lesioning in the nucleus accumbens] Ross Fiziol Zh Im I M Sechenova. 88(5):663–9.
  30. Wiener, S.I., Rondi-Reig, L., Zugaro, M.B. Comprendre les fonctions cognitives grâce à l’enregistrement de l’activité neuronale et l’analyse comportementale chez le rat libre de ses mouvements : les bases physiologiques des représentations internes de la topographie de l’environnement. Intellectica 32: 9–44.
  31. Zugaro, M.B., Berthoz, A., Wiener S.I. Background, but not foreground, spatial cues are taken as references for head direction responses by rat anterodorsal thalamus neurons. J. Neurosci. 21: RC154(1–5)
  32. Shibata, R., Mulder, A.B., Trullier, O., Wiener, S.I. Position sensitivity in phasically discharging nucleus accumbens neurons of rats alternating between tasks requiring complementary types of spatial cues. Neurosci. 108:391–411
  33. Zugaro, M.B., Tabuchi, E., Fouquier, C., Berthoz, A., Wiener, S.I. Active locomotion increases peak firing rates of anterodorsal thalamic head direction cells. J. Neurophysiol. 86:692–702
  34. Albertin, S.V., Mulder, A.B., Tabuchi, E., Zugaro, M.B., Wiener, S.I. Lesions of the medial shell of the nucleus accumbens impair rats in finding larger rewards, but spare reward-seeking behavior. Behavioral Brain Research 117:173–183
  35. Tabuchi, E., Mulder, A.B., Wiener, S.I. Position and behavioral modulation of synchronization of hippocampal and accumbens neuronal discharges in freely moving rats. Hippocampus 10:717–728
  36. Zugaro, M.B., Tabuchi, E., Wiener, S.I. Influence of conflicting visual, inertial and substratal cues on head direction cells. Exp. Brain Res. 133:198–208
  37. Trullier, O., Shibata, R., Mulder, A.B., Wiener, S.I. Hippocampal neuronal position selectivity remains fixed to room cue in rats alternating between place navigation and beacon approach tasks. Eur. J. Neurosci. 11(12):4381–8
  38. Gavrilov, V.V., Wiener, S.I., Berthoz, A. Discharge correlates of hippocampal complex spike neurons in behaving rats passively displaced on a mobile robot. Hippocampus 8:475–490
  39. Trullier, O., Wiener, S., Berthoz, A., and Meyer, J.-A. Biologically-based artificial navigation systems: Review and prospects. Progress in Neurobiology 51:483–544
  40. Wiener, S.I. Spatial, behavioral and sensory correlates of hippocampal CA1 complex spike cell activity: Implications for information processing functions. Progress in Neurobiology 49:335–361
  41. Gavrilov, V.V., Wiener, S.I., Berthoz, A. Whole body rotations enhance hippocampal theta rhythmic slow activity in awake rats passively transported on a mobile robot. Ann. N.Y. Acad. Sci. 781: 385–398
  42. Korshunov, V.A., Wiener, S.I., Korshunova, T.A., Berthoz, A. Place- and behavior-independent sensory triggered discharges in rat hippocampal CA1 complex spike cells. Exp. Brain Res. 109:169–173
  43. Wiener, S.I., Korshunov, V., Garcia, R., Berthoz, A. Inertial, substratal and landmark cue control of hippocampal CA1 place cells. Eur. J. Neurosci., 7(11):2206–2219
  44. Wiener, S.I., Korshunov, V.A. Place-independent behavioral correlates of hippocampal neurons in behaving rats. Neuroreport 7:183–188
  45. Gavrilov, V.V., Wiener, S.I., Berthoz, A. Enhanced hippocampal theta EEG during whole body rotations in awake restrained rats. Neurosci. Lett. 197:239–241
  46. Jung, M., Wiener, S.I., McNaughton, B.L. Comparisons of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat. J. Neurosci. 14:7347–7356
  47. Wiener, S.I. Spatial and behavioral correlates of striatal neurons in rats performing a self-initiated navigation task. J. Neurosci. 13:3802–3817
  48. Otto, T., Eichenbaum, H., Wiener, S. and C.G. Wible Learning-related patterns of CA1 spike trains parallel stimulation parameters optimal for inducing hippocampal long-term potentiation. Hippocampus 1:181–192
  49. Wiener, S.I., C.A. Paul and H. Eichenbaum Spatial and behavioral correlates of hippocampal neuronal activity. J. Neurosci. 9:2737–2763
  50. Eichenbaum, H., S.I. Wiener, M.L. Shapiro and N.J. Cohen The organization of spatial coding in the hippocampus: A study of neural ensemble activity. J. Neurosci. 9:2764–2775
  51. Eichenbaum, H. and S.I. Wiener Is place the (only) functional correlate? Psychobiology 17:217–220
  52. Wiener, S.I., J.I. Johnson and E.-M. Ostapoff Organization of postcranial kinesthetic projections to the ventrobasal thalamus in raccoons. J. Comp. Neurol. 258:496–508
  53. Wiener, S.I., J.I. Johnson and E.-M. Ostapoff Demarcations of the mechanosensory projection zones in the raccoon thalamus, shown by cytochrome oxidase, acetylcholinesterase, and Nissl stains. J. Comp. Neurol. 258:509–526
  54. Wiener, S.I. and P.H. Hartline Perioral somatosensory but not visual inputs to the flank of the mouse superior colliculus. Neurosci. 21:557–564
  55. Wiener, S.I. Laminar distribution and patchiness of cytochrome oxidase in mouse superior colliculus. J. Comp. Neurol. 244:137–148

Susan Sara

Neuromodulation and Cognitive Processes

The neurobiological basis of memory formation and retrieval has been the major focus of my research over the past four decades.  Combining in vivo electrophysiology and pharmacology with astute behavioral analysis, my thesis and subsequent publications provided early challenges the consolidation hypothesis.  We published the first paper demonstrating ‘reconsolidation after reactivation of memory’ and showed the importance of the noradrenergic system in this reconsolidation processs.  We study the role of the noradrenergic locus coeruleus (LC) in cognitive processes by recording the activity of neurons in this nucleus in behaving rats, engaged in various cognitive tasks. In this way we have elucidated the functional role of this tiny nucleus in modulating encoding and off-line memory consolidation, in concert with activity in frontal cortex and hippocampus. More recently, we have been investigating the role of sleep oscillations and associated LC activity in modulation of memory processes.  Currently we are using optogenetic methods to stimulate or inhibit activity of LC neurons at critical periods during learning or during off-line memory consolidation.

Born and educated in New York City, Susan J. Sara received a BA in psychology from Sarah Lawrence College and a PhD from University of Louvain (Belgium). After post doctoral studies at Oxford University and NYU Medical School, she was recruited into the CNRS (France). She founded the group ‘Neuromodulation and Cognitive Processes’ at the University Paris VI, which she headed until her retirement. She is currently Directrice de Recherche Emerite at the College de France and Adjunct Professor at New York University Medical School. SJS was a visiting Professor at the Institute of Neurosciences in Shanghai and at Yamaguchi Medical School, Japan and a visiting scientist at the Weizmann Institute, Israel. She is past president of the European Brain and Behavior Society and has served as Chair of FENS_IBRO schools committee, Chair of IBRO Alumni committee, FENS programme committee, FENS executive Committee. She has served on the Scientific Advisory Board of the Nencki Institute (Poland) and the Max Planck Insitute for Biological Cybernetics (Tuebingen), as well as on several advisory panels for the EU and ERC. She is past editor of Neural Plasticity and currently associate editor of Frontiers in Behavioral Neuroscience.

  1. Poe GR, Foote S, Eschenko O, Johansen JP, Bouret S, Aston-Jones G, Harley CW, Manahan-Vaughan D, Weinshenker D, Valentino R, Berridge C, Chandler DJ, Waterhouse B, Sara SJ. Locus coeruleus: a new look at the blue spot. Nat Rev Neurosci. 21(11):644-659.
  2. Swift KM, Gross BA, Frazer MA, Bauer DS, Clark KJD, Vazey EM, Aston-Jones G, Li Y, Pickering AE, Sara SJ, Poe GR. Abnormal Locus Coeruleus Sleep Activity Alters Sleep Signatures of Memory Consolidation and Impairs Place Cell Stability and Spatial Memory. Curr Biol. 28:3599-3609.
  3. Xiang L, Harel A, Gao HG, Pickering AE, Sara SJ, Wiener SI. Behavioral correlates of activity of optogenetically identified locus coeruleus noradrenergic neurons in rats performing t-maze tasks. Scientific Reports 9:1361.
  4. Sara SJ. Sleep to remember. Journal of Neuroscience 37(3):457–63
  5. Sara SJ. Response from Dual Perspective Companion Author. Journal of Neuroscience 37(3):471
  6. Sara SJ. Locus coeruleus reports changes in environmental contingencies. Behavioral and Brain Sciences 39:e223
  7. Novitskaya Y, Sara SJ, Logothetis NK, Eschenko O. Ripple-triggered stimulation of the locus coeruleus during post-learning sleep disrupts ripple/spindle coupling and impairs memory consolidation. Learning and Memory 23(5):238–48
  8. Sara SJ. Locus Coeruleus in time with the making of memories. Current Opinion in Neurobiology 35:87–94
  9. Doucet EL, Bobadilla AC, Houades V, Lanteri C, Godeheu G, Lanfumey L, Sara SJ, Tassin JP. Sustained impairment of α2A-adrenergic autoreceptor signaling mediates neurochemical and behavioral sensitization to amphetamine. Biol Psychiatry. 74(2):90–8
  10. Sara SJ, Bouret S. Orienting and reorienting: the Locus coeruleus mediates cognition through arousal, Neuron 76:130-141.
  11. Eschenko, O; Magri, C, Panzeri, S, Sara, SJ Noradrenergic Neurons of the Locus Coeruleus are Phase-locked to Cortical Up-Down States during sleep. Cerebral Cortex
  12. Gais S, Rasch B, Dahmen JC, Sara S, Born J. The memory function of noradrenergic activity in non-REM sleep. J Cogn Neurosci. 23(9):2582–92
  13. Sara SJ. Reactivation, retrieval, replay, and reconsolidation in and out of sleep: connecting the dots. Front. Behav. Neurosci. 4:185.
  14. Ramadan, W., Eschenko, O., & Sara, SJ. Hippocampal sharp wave/ripples during sleep for consolidation of associative memory, Front. Behav. Neurosci.
  15. Sara S.J. The locus coeruleus and noradrenergic function. Nature Reviews in Neuroscience 10:211–223.
  16. Molle, M, Eschenko, O. Gais S., Sara, SJ & Born J. The influence of learning on sleep slow oscillations and associated spindles and ripples in humans and rats. Eur J Neurosci 29:1071–1081.
  17. Eschenko, O. Sara, SJ Learning-dependent, transient increase of activity in noradrenergic neurons of locus coeruleus during slow wave sleep in the rat: Brainstem-cortex interplay for memory consolidation? Cerebral Cortex 18:2596–2603.
  18. Eschenko, O., Ramadan, W., Molle, M., Born, J. & Sara, SJ Sustained increase in hippocampal sharp-wave ripple activity during slow wave sleep after learning. Learning & Memory 15(4):222–228.
  19. Chen, F & Sara, SJ Locus coeruleus activation by footshock or electrical stimulation inhibits amygdale neurons. Neuroscience 144:472–481.
  20. Sara, S.J. & Hars, B. In memory of consolidation Learning & Memory 5:515–521
  21. Eschenko, O. Molle, M. Born, J. & Sara, SJ Elevated spindle density after learning and retrieval in rats. J. Neuroscience 26:12914–12920.
  22. Molle, M., Eschenko, O. Sara, SJ , Born, J.Hippocampal sharp wave-ripples linked to slow oscillations in rat slow-wave sleep. J Neurophysiol. 96:62–70.
  23. Torres-Garcia, M. Lelong, J & Sara, SJ Reconsolidation after remembering requires NMDA receptors Learning & Memory 12:18–22.
  24. Bouret S. & Sara, SJ. Network reset: a new over-arching theory of locus ceruleus-noradrenergic function. Trends in Neuroscience 11,.
  25. Tronel S. Feenstra, M. & Sara, S.J. Noradrenergic action in the prelimbic cortex in the late stages of memory consolidation, Learning & Memory 453–458.
  26. Bouret, S. & Sara, SJ Reward expectation, attention, and locus coeruleus-medial frontal cortex interplay during learning, Eur J Neurosci 20:791–802.
  27. Bouret,S. A. Duval, S. Onat, S. J. Sara Activation of Locus Coeruleus by the Central Nucleus of the Amygdala, J. Neuroscience 23:3491–97.
  28. Foley, AG Hedigan, K. Roullet, P. Moricard, Y. Murphy, K. Sara, SJ, Regan, CM Consolidation of memory for odour-reward association requires transient polysialyation of the neural cell adhesion molecule in the rat hippocampal dentate gyrus. J. Neuroscience Research 74:570–576.
  29. Tronel S. & Sara, SJ Blockade of NMDA receptors in prelimbic cortex induces an enduring amnesia for odor-reward associative learning. J Neuroscience 23:5472–5476.
  30. Tronel, S. & Sara, S.J. Mapping of olfactory memory circuits: region specific c-fos activation after odor-reward associative learning or after its retrieval. Learning & Memory 9:4.
  31. Bouret, S. & Sara, SJ Locus coeruleus activation modulates firing rate and temporal organization of odor-induced single cell responses in rat piriform cortex. Eur J Neurosci 12:2371–82.
  32. Sara, SJ Retrieval and reconsolidation : toward a neurobiology of remembering. Learning & Memory 7:73–84.
  33. Sara, S.J. Strengthening the shaky trace through retrieval. Nature Reviews Neuroscience, , 1:212–214
  34. Shinba, T. Briois,L. & Sara, S.J. Spontaneous and auditory-evoked activity of the medial agranular cortex as a function of arousal state in the freely moving rat: interaction with locus coeruleus activity, Brain Research ; 887:293–300.
  35. Roullet, P. Sara, SJ Consolidation of Memory after its reactivation: Involvement of beta noradrenergic receptors in the late phase. Neural Plasticity 6:63–68.
  36. Roullet, P. Bourne, R., Moricard, Y. Stewart, M. & Sara, SJ Learning-induced plasticity of NMDA receptors is task and region-specific Neuroscience 89:1145–1150
  37. Przybyslawski, J , Roullet, P. , Sara, SJ Attenuation of emotional and nonemotional memories after their reactivation: role of Beta adrenergic receptors.J. Neuroscience 19:6623–6628.
  38. SARA, SJ., Roullet, P., Przybyslawski, J., Consolidation of memory for odour-reward association: beta adrenergic receptor involvement in the late phase. Learning & Memory 6:88–96.
  39. Lestienne, R. Hervé, A. Robinson, D. Brios. L. & SARA,SJ, Slow oscillations as aprobe of the dynamics of the locus coeurleus-frontal cortex interaction in anesthetized rats. J. Physiol (Paris) 91:273–284.
  40. Sara, SJ Learning by Neurones: role of attention, reinforcement and behaviour. C.R.Acad Sci 321:193–198.
  41. Przybyslawski, J. & Sara, SJ Reconsolidation after reactivation of memory. Behavioral Brain Research 84:241–246.
  42. Alexinsky, T., Przybyslawski, J., Mileusnic, R., Rose, S, & Sara, SJ, Antibody to Day-Old Chick Brain Glycoprotein Produces Amnesia in Adult Rats, Neurobiology of Learning & Memory 67:14–20.
  43. Kitchigina V. Vankov, A. Harley, C. & Sara, SJ; Novelty-elicited, norepinephrine-dependent enhancement of excitability in the rat dentate gyrus. European J. Neuroscience 9:41–47.
  44. Roullet, P, Mileusnic, R. Rose, S, & Sara, SJ, Neural cell adhesion molecules play a role in rat memory formation in appetitive as well as aversive tasks. Neuroreport 8:1907–1911
  45. Sara, S.J., Dyon-Laurent, C. & Hervé, A. Novelty seeking behavior in the rat is dependent upon the integrity of the noradrenergic system. Cognitive Brain Research 2:181–187.
  46. Vankov, A. Hervé-Minvielle, A. & Sara, SJ. Response to novelty and its rapid habituation in locus coeruleus neurons of the freely-exploring rat. European J. Neuroscience 7:1180–1187.
  47. Sara, SJ & Hervé-Minvielle, A. Inhibitory influence of frontal cortex on locus coeruleus. PNAS 92:6032–6035.
  48. Hervé-Minvielle, A. & Sara, SJ Rapid habituation of auditory responses of locus coeruleus cells in anethestized and awake rats, Neuroreport 6:45–50
  49. Dyon-Laurent, C. Hervé, A., Sara, S.J. Noradrenergic hyperactivity in hippocampus after partial denervation: pharmacological, behavioral and electrophysiological studies. Exp Brain Res
  50. Buda, M, Laucher, J, Devauges, V, Barbagli, B, Blizard, D, & Sara, SJ. Central noradrenergic reactivity to stress in Maudsley rat strains Neuroscience Letters 33–36.
  51. Sara, S.J., Vankov, A., Hervé, A., Locus Coeruleus evoked responses in behaving rats: a clue to the role of noradrenaline in memory. Brain Research Bulletin 35:457–465.
  52. Sara, SJ, Devauges, V., Biegon, A., & Blizard, D. The Maudsley rat strains as a probe to investigate noradrenergic-cholinergic interaction in cognitive function. J. Physiol (Paris) 88:337–345.
  53. Sara, S. J., Devauges, V. & Biegon, A. Maudsley rat strains, selected for differences in emotional responses, differ in behavioral response to clonidine and alpha2 receptor binding in the locus coeruleus, Behavioral Brain Research 57:101–104.
  54. Dyon-Laurent, C, Romand, S, Biegon, A & Sara, S.J. Functional reorganization of the noradrenergic system after partial fornix section: a behavioral and autoradiographic study. Exp Brain Res 96:203–211.
  55. Sara, S.J., Dyon-Laurent, C. Guibert, B. & Leviel, V. Noradrenergic hyperactivity after partial fornix section: role in cholinergic dependent memory performance. Exp Brain Res 89:125–132.
  56. Messing, R., Devauges, V., Sara, S.J. The limbic forebrain neurotoxin trimethyltin reduces behavioral supression by clonidine. Pharmacology, Biochemistry & Behavior 42:313–316.
  57. Harley, C. & Sara, S.J. Locus coeruleus bursts induced by glutamate trigger delayed perforant path spike amplitude potentiation in the dentate gyrus. Exp Brain Res 89:581–587.
  58. Venault, P. Jacquot, F., Save, E., Sara, S., Chapoutier, G. Anxiogenic-like effects of yohimbine and idazoxan in two behavioral situations in mice. Life Sciences
  59. Poincheval-Fuhrman, S. & Sara, S.J. Chronic nicotine ingestion improves radial maze performance in rats, Behavioural Pharmacology 4:534–539.
  60. Devauges, V. and Sara, S.J. Activation of the noradrenergic system facilitates an attentional shift in the rat. Behavioral Brain Research 39:19–28.
  61. Chapoutier, G. Jacquot, F. Save, E., Venault, P., Sara, S.J. Different effects of yohimbine and idazoxan in the light-dark choice procedure. Behavioural Pharmacology 1:459–461.
  62. Richter-Levin, G. Segal, M. Sara, S.J. Idazoxan, an alpha2 antagonist enhances EPSP to spike coupling, Brain Research 540:291–294.
  63. Devauges, V. and Sara, S.J. Memory retrieval enhancement by locus coeruleus stimulation: evidence for mediation by beta receptors. Behavioral Brain Research 43:93–97.
  64. Sara, S.J. and Bergis, O. Enhancement of excitability and inhibitory processes in the hippocampal dentate gyrus by noradrenaline: a pharmacological study in awake rats. Neuroscience Letters 126:1–5.
  65. Sara, S.J. & Segal, M. Plasticity of sensory responses in the locus coeruleus: significance for cognition. Progress in Brain Research 88:571–585.
  66. Ammassari, M., Maho, C. & Sara, S.J. Clonidine reverses spatial learning deficits and reinstates theta frequencies in rats with partial fornix section. Behavioral Brain Research 45:1–8.
  67. Sara, S.J., Devauges, V. Priming stimulation of locus coeruleus facilitates memory retrieval in the rat. Brain Research 438:299–303.
  68. Sara, S.J. Glucose effects on firing rate of neurons of the locus coeruleus : another attempt to put memory back in the brain. Neurobiology of Aging 9:730–732.
  69. Sara, S.J. and Devauges, V. Idazoxan, an alpha2 antagonist, facilitates memory retrieval in the rat. Behavioral and Neural Biology 51:328–338.
  70. Sara S.J. Noradrenergic-cholinergic interactions : its possible role in memory dysfunctions associated with senile dementia. Archives of Gerontology 99–108.
  71. Le Roch, K., Riche, D., Sara, S.J. Persistence of habituation deficits after neurological recovery from severe thiamine deprivation. Behavioral Brain Research 23.
  72. Dekeyne, A., Deweer, B., Sara, S.J. Background stimuli as a reminder after spontaneous forgetting : potentiation by stimulation of the mesencephalic reticular formation. Psychobiology 15:161–166.
  73. Sara, S.J. Forgetting of conditioned emotional response and its alleviation by pretest amphetamine. Physiological Psychology 12:17–22.
  74. Deweer, B. and Sara, S.J. Background stimuli as a reminder after spontaneous forgetting: role of duration cuing and cuing-test interval. Animal Learning & Behavior 12:238–247.
  75. Sara, S.J, Grecksch, G. and Leviel, V. Intercerebral ventricular apomorphine alleviates spontaneous fotgetting and increases cortical noradrenaline. Behavioral Brain Research 13:43–52.
  76. Sara, S. J. The locus coeruleus and cognitive function: Attempts to relate noradrenergic enhancement of signal/noise in the brain to behavior. Physiological Psychology 13:151–162.
  77. Sara, S.J. Haloperidol facilitates memory retrieval in the rat., Psychopharmacology 89:307–310.
  78. Sara, S.J., David-Reacle, M., Weyers, M. and Giurgea, C. Piracetam facilitates retrieval but does not impaired extinction of bar pressing in rats. Psychopharmacology 61:71–75.
  79. Sara, S.J., Deweer, B. and Hars, B. Reticular stimulation facilitates retrieval of a “forgotten” maze habit. Neuroscience Letters 18:211–217.
  80. Deweer, B., Sara, S.J. and Hars, B. Contextual cues and memory retrieval in rats: alleviation of forgetting by a pretest exposure to background stimuli. Animal Learning & Behavior 8:265–272.
  81. Sara, S.J. Facilitation of memory retrieval by etiracetam nootropic drug. Psychopharmacology 68:235–241.
  82. Sara, S.J. and David-Remacle, M. Discrimination learning, behavioral stategies and long term retention in hippocampal lesioned rats. Physiological Psychology 9:37–48.
  83. Sara, S.J. Memory deficits in rats with hippocampal and cortical lesions: retrograde effects. Behavioral and Neural Biology 32:504–509.
  84. Sara S.J., Barnett, J. and Toussaint, P. Facilitation of appetitive brightness discrimination by lysine vasopressin. Behavioral Processes 7:157–167.
  85. Sara, S.J. and Deweer, B. Facilitation of retrieval of a “forgotten” maze task by pretest amphetamine. Behavioral & Neural Biology 36:146–160.
  86. Sara, S.J. and Remacle, J.F. Strychnine-induced passive avoidance facilitation: a retieval effect. Behavioral Biology 19:465–475.
  87. Sara, S.J. et David-Remacle, M. Recovery from electroconsulsive shock amnesia by exposure to the training environment: pharmacological enhancement by Piracetam. Psychopharmacology 36:59–66.
  88. Sara, S.J. Delayed development of amnestic behaviour after hypoxia. Physiology and Behaviour 13:693–696.
  89. Sara, S.J., David-Remacle, M. and Lefèvre, D. Passive avoidance behaviour in rats after electroconvulsive shock: facilitative effect of response retardation. Journal of Comparative and Physiological Psychology 89:489–497.
  90. Sara, S.J. and Lefèvre, D. Reexamination of the role of familiarization in retrograde amnesia in the rat. Journal of comparative and Physiological Psychology 85:361–364.
  91. Sara, S.J. Recovery from hypoxia and ECS induced amnesia after a single exposure to the training environment. Physiology and Behaviour , l0:85–89.
  92. Sara, S.J. Progressive development of avoidance response after training, ECS and repeated testing. Bulletin of the Psychonomic Society 2:l34-l36.
  93. Sara, S.J. and Lefèvre, D. Hypoxia induced amnesia in one trial learning and pharmacological protection by Piracetam. Psychopharmacologia 25:32–40.

Book Chapters

  1. Sara, S.J. Reconsolidation: historical perspective and theoretical aspects. In H.L. Roediger, III (Ed.), Cognitive Psychology of Memory. Vol. [1] of Learning and Memory: Comprehensive Reference, 4 vols. (J.Byrne Editor). Oxford: , Elsevier.
  2. Sara, SJ Consolidation as concept. In: Science of Memory: Concepts HR Roediger III, Y Dudai, and SM Fitzpatrick – Editors Oxford University Press,
  3. Sara, S.J. & Gisquet-Verrier, P. La Reconstruction de la Mémoire, Science & Vie, June,.
  4. Sara S.J. Noradrenaline and memory: neuromodulatory effects on retrieval. In “Memory: Neurochemical and clinical aspects”, J. Weinman and J. Hunter (eds), Harwood Academic Publishers: London , pp 105–128.
  5. Sara S.J. Interaction des systèmes noradrénergiques et cholinergiques au cours des troubles de la mémoire. In “Mémoire et Vieillissement : approche méthodologique”, Collection de l’Institut de Recherches Internationales Servier, Doin Paris, pp. 105–116.
  6. Sara, S.J., Devauges, V. and Segal, M. Locus coeruleus engagement in memory retrieval and attention. In “Progress in Catecholamine Research”, Alan R. Liss (ed) pp. 155–161.
  7. Sara, S. J. et Segal, M. The locus coeruleus in learning and memory retrieval. In H. Matthies (Ed) Learning and Memory: Mechanisms of Information Processing in the Nervous System : Oxford, Pergamon Press.
  8. Sara, S.J. Noradrenergic modulation of selective attention : its role in memory retrieval. In D. Olton, E. Gamzu and S. Corkin (Eds), Memory dysfunctions: An integration of Animal and Human Research from preclinical and clinical perspectives. Ann NY Acad Science 444:178–193.
  9. Sara, S.J. Selective attention, memory and the locus coeruleus. In P. Schmidt and B. Will (Eds) Brain Plasticity, Learning and Memory, Plenum Press: New York, 211–218, l985.

Technology

We use state-of-the art technologies. Our 128 channel recording systems, multisite silicon probes and custom designed tetrode/octrode microdrives allow us to simultaneously record from dozens of neurons across multiple brain areas, such as hippocampal place cells and prefrontal cell assemblies. To train animals in spatial learning tasks, we use custom automated setups ranging from standard T-mazes to miniature treadmills transported by model trains. Our data processing infrastructure includes a 96-core computer cluster and 4 centralized storage servers. To process, visualize and analyze our data, we use our custom application suite NeuroSuite and Matlab toolbox FMAToolbox.

Team

Permanent Researchers

Michaël Zugaro

Team Leader

Sidney Wiener

Research Director

Susan Sara

Professor NYU

Current Members

Ombeline Hoa

Postdoc

Maxime Linard

Césure

Raphaël Brito

PhD Student

Linda Kokou

PhD Student

Théo Mathevet

PhD Student

Alumni

Virginie Oberto

PhD-Postdoc
2012-2021

Alexandra Dolzhina

M2 Student
2018-2019

Laura Sylvander

M2 Student
2017

Antoine Harel

M2 Student
2016

Karim Benchenane

Postdoc
2006-2009

Ariane Bochereau

PhD-Postdoc
2017-2021

Diane Vilmer

Engineer Student
2018

Jumpei Matsumoto

Invited Researcher
2015-2017

Marie Goutierre

M2 Student
2013

Adrien Peyrache

PhD Student
2005-2009

Céline Boucly

PhD Student
2017-2020

Céline Drieu

PhD-Postdoc
2012-2018

HongYing Gao

Postdoc
2012-2016

Karim El Kanbi

M2 Student
2012

Mehdi Khamassi

PhD Student
2003-2007

Sara Simula

M2 Student
2020

Gabriel Makdah

M2 Student
2018

Nicolas Maingret

PhD Student
2011-2016

Anne Cei

PhD-Postdoc
2006-2014

Francesco Battaglia

Postdoc
2004-2005

Nadia Benabdallah

PhD Student
2016-2020

Fanny Demars

M2 Student
2017

Anna Segú

M1 Student
20215-2016

Gabrielle Girardeau

PhD-Postdoc
2006-2012

Eulalie Leroux

M2 Student
2018-2019

Liyang Xiang

PhD Student
2013-2017

Margot Tirole

M2 Student
2016

Erika Cerasti

Postdoc
2009-2012

Group Pictures

Team-2021a-001-500x563
2021a
Team-2021b-001-500x563
2021b
2017
2015
2011

Hippocampus

Paris has a hippocampus!

It is clearly visible on the pavement of rue Soufflot, in front of the Panthéon – just a few hundred meters from our lab.​

Positions

Postoctoral Fellows

Two post-doctoral positions are available to investigate the network mechanisms of memory formation and consolidation. One candidate should have a strong background in recordings of large neuronal ensembles and optogenetics in freely behaving rodents. Good Matlab programming skills are welcome. The other candidate should have a solid background in data analysis of brain signals. Experimental training would also be extremely useful. Both positions are available for up to 3 years. Selection will be open until the positions are filled. Applicants should send their CV, a cover letter detailing their research experience and interests, and two letters of reference.

PhD Students

PhD grants are awarded by the ED3C Doctoral School in July. Typical candidates are M2 students who have performed their research internship in the lab, and have been trained and prepared for their PhD project. However, candidates who can apply for independent funding are welcome to contact us.

Research Internships

Students are welcome to contact us for research internships.

Contact

Brain Rhythms and Neural Coding of Memory
Center for Interdisciplinary Research in Biology
Collège de France, CNRS UMR 7241, INSERM U 1050
11, place Marcelin Berthelot
75005 Paris, France