Brain Rhythms and Neural Coding of Memory

Principal Investigator: Michaël ZUGARO, DR2 Cnrs

Our research targets the neuronal mechanisms of integration of multisensorial information from the environment with internal signals (such as emotions) for the elaboration, memorization and recall of spatial representations. The goal of our studies is to better understand the neural bases of cognitive processes necessary for an animal to survive in its environment, and their relations to adaptive behaviours and learned and remembered associations. A principal approach is multichannel recordings of ensemble neuronal activity and more global brain activity in the form of local field potential oscillations in the freely moving animal performing orienting, learning and memory tasks. This work focusses on the hippocampal system (affected in Alzheimer's disease) which is distinguished by the presence of neurons responsive to the position and direction of the head in space. These provide tractable experimental models for high-level cognitive representations at the level of single neurons and neural networks. To understand how this activity is implicated in memorization and in informing ongoing behavior, we make simultaneous recordings in downstream structures such as prefrontal cortex (affected in schizophrenia) and ventral striatum (affected in Parkinson's disease). By correlating neurophysiological activity with behavioral measures we determine the neural bases of cognitive function.

Sid - Fig1 - rat
The 8 arm radial maze tests how well the rat learns the locations of chocolate treats.


Neuroengineering analyses of neural ensemble activity
To understand the nature of coding by simultaneously active neurons and the coordination of activity in connected areas of brain networks by synchronization with brain rhythms and other events measured in local field potentials (LFPs). Recent work has shown how hippocampal signals help form permanent memory traces in the neocortex. Of particular interest is the replay of experience-related neuron activation sequences during 'sharp wave/ripples' during slow wave sleep. The role of neuromodulators such as noradrenaline is investigated.
Collaborators: Venance team, CIRB; Rouach team, CIRB; Pr. G. Buzsáki, NYU, USA; Dr. K. Benchenane, EPSCI; Dr. O. Eschenko, Max Planck Inst, Tubingen.

Modelling studies of behavior and neural activity

Hidden Markov models and Bayesian analyses permit estimation of hidden variables such as the ongoing strategy of a rat performing a maze task. Models permit to determine how well neurophysiological measures correspond to such cognitive parameters.
Collaborators: Dr. Jacques Droulez, CNRS, Paris; Dr Mehdi Khamassi, ISIR, UPMC.

In order to help design more effective control systems for autonomous mobile robots, we discover brain mechanisms for decision-making and planning and transfer this knowledge to roboticians.
Collaborators: Prs. M. Quoy, & P. Gaussier, ETIS, Univ Cergy; Drs. E. Save, B. Poucet, CNRS, Marseille; Dr. M. Humphries Univ Manchester, UK.

Neural bases of spatial orientation
Multisensory fusion in the elaboration of brain representations of head position and direction
Research efforts have demonstrated mechanisms of fusion of multi-sensory signals such as visual landmark cues, head acceleration information detected through the vestibular end-organs in the inner ear, optic field flow and locomotion.
Collaborators: Pr. Alain Berthoz, Professor Hon., Collège de France; Dr. A. Arleo, CNRS, UPMC, Paris 6

Visual handicap and cortical plasticity
With optical imagery we will visualize functional maps in the mouse visual cortex and characterize the general rules governing their development including the roles of homeoproteins (with the Prochiantz team) and connexins (with the Rouach team). Another project will study the cortical compensatory processes that develop after blindness through engagement of audition.

Trajectories represented by sequences of hippocampal cell assemblies

During exploration, hippocampal place cells discharge fast sequences of action potentials that code for the ongoing spatial trajectory. Each sequence occurs during a single cycle of the ongoing 'theta' oscillation (~125 ms), and is thus referred to as a 'theta sequence'. To determine the mechanisms underlying the formation of theta sequences, we record from hippocampal cell ensembles in rats trained to run on a miniature treadmill mounted on a model train, and transport the rats backwards so that they experience the familiar environment in reverse order. Our data will confront models predicting that theta sequences should reverse with those predicting they should remain unchanged, providing further insight into the mechanisms of theta sequence formation.

Wiener Fig2a




Selected Publications 2005-2019

- Todorova, R., and Zugaro, M. (2019). Isolated cortical computations during delta waves support memory consolidation. Science 366, 377–381.

- Drieu, C., and Zugaro, M. (2019). Hippocampal Sequences During Exploration: Mechanisms and Functions. Front Cell Neurosci 13, 232. 

- Wiener-Vacher, S.R., Wiener, S.I., Ajrezo, L., Obeid, R., Mohamed, D., Boizeau, P., Alberti, C., and Bucci, M.P. (2019). Dizziness and Convergence Insufficiency in Children: Screening and Management. Front Integr Neurosci 13, 25.

- Drieu, C., Todorova, R., and Zugaro, M. (2018). Nested sequences of hippocampal assemblies during behavior support subsequent sleep replay. Science 362, 675–679.

- Todorova, R., and Zugaro, M. (2018). Hippocampal ripples as a mode of communication with cortical and subcortical areas. Hippocampus.

- Maingret, N., Girardeau, G., Todorova, R., Goutierre, M. & Zugaro, M. (2016), Hippocampo-cortical coupling mediates memory consolidation during sleep. Nat. Neurosci. May 16.

- Albertin, S. V., and Wiener, S. I. (2015). Neuronal Activity in the Nucleus Accumbens and Hippocampus in Rats during Formation of Seeking Behavior in a Radial Maze. Bull. Exp. Biol. Med. 158, 405–409.

- Catanese, J., Viggiano, A., Cerasti, E., Zugaro, M. B., and Wiener, S. I. (2014), Retrospectively and prospectively modulated hippocampal place responses are differentially distributed along a common path in a continuous T-maze. J. Neurosci. 34, 13163–13169.

- Girardeau G., Cei A. & Zugaro M. (2014), Learning-induced plasticity regulates hippocampal sharp wave-ripple drive. Journal of Neuroscience 34(15):5176-83.

- Cattan S., Bachatene L., Bharmauria V., Jeyabalaratnam J., Milleret C. & Molotchnikoff S. (2014), Comparative analysis of orientation maps in areas 17 and 18 of the cat primary visual cortex following adaptation. Eur. J. Neurosci. 40, 2554–2563.

- Cei A., Girardeau G., Drieu C., Kanbi KE & Zugaro M. (2014), Reversed theta sequences of hippocampal cell assemblies during backward travel. Nature Neuroscience 17(5):719-24

- Wiener-Vacher S. R., Hamilton D. A. & Wiener S. I. (2013), Vestibular activity and cognitive development in children: Perspectives. Frontiers in Integrative Neuroscience, vol.7, article 92, p. 1-13.

- Arleo A., Déjean C., Allegraud P., Khamassi M., Zugaro M. B. & Wiener S. I. (2013), Optic flow stimuli update anterodorsal thalamus head direction neuronal activity in rats. J Neurosci. 33(42):16790-5.

- Catanese J., Cerasti E., M. Zugaro M., Viggiano A. & Wiener S. I. (2012), Dynamics of decision-related activity in prospective, hippocampal place cells. Hippocampus 22 (9):1901-11.

- Sara S. J. & Bouret S. (2012), Orienting and reorienting: the locus coeruleus mediates cognition through arousal. Neuron, 76(1):130-41.

- Eschenko O., Magri C., Panzeri S. & Sara S. J. (2012), Noradrenergic neurons of the locus coeruleus are phase locked to cortical up-down states during sleep. Cereb Cortex, 22(2):426-35.

- Battaglia F. P., Benchenane K., Sirota A., Pennartz C. M. & Wiener S. I. (2011), The hippocampus: Hub of brain network communication for memory. Trends Cogn Sci 15:310-318.

- Girardeau G. & Zugaro M. B. (2011), Hippocampal ripples and memory consolidation. Current Opinion in Neurobiology. 21(3):452-9.

- Peyrache A., Benchenane K., Khamassi M., Wiener S. I. & Battaglia F. P. (2010), Sequential reinstatement of neocortical activity during slow oscillations depends on cells' global activity. Front Syst Neurosci, 3:18.

- Benchenane K., Peyrache A., Khamassi M., Tierney P., Gioanni Y., Battaglia F. P. & Wiener S. I. (2010), Coherent theta oscillations and reorganization of spike timing in the hippocampal-prefrontal network upon learning. Neuron, 66;921-36.

- Sara S. J. (2009), The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci, 10(3):211-23.

- Ramadan W., Eschenko O. & Sara S. J. (2009), Hippocampal sharp wave/ripples during sleep for consolidation of associative memory. PLoS One, 4(8):e6697.

- Girardeau G., Benchenane K., Wiener S. I., Buzsaki G. & Zugaro M. B. (2009), Selective suppression of hippocampal ripples impairs spatial memory. Nat Neurosci, 12:1222-1223.

- Peyrache A., Benchenane K., Khamassi M., Wiener S. I. & Battaglia F. P. (2009), Principal component analysis of ensemble recordings reveals cell assemblies at high temporal resolution. J Comput Neurosci, Jun 16.

- Peyrache A., Khamassi M., Benchenane K., Wiener S. I. & Battaglia F. P. (2009), Replay of rule-learning related neural patterns in the prefrontal cortex during sleep. Nat Neurosci, 12:919-926.

- Khamassi M., Mulder A. B., Tabuchi E., Douchamps V. & Wiener S. I. (2008), Anticipatory reward signals in ventral striatal neurons of behaving rats. Eur J Neurosci, 28:1849-1866.


Group leader:
Zugaro Michaël, DR2 CNRS

Senior researchers:
Wiener Sidney, DR1 CNRS
Susan Sara, NYU (prof. invitée)
Alain Berthoz, Pr émérite CdF

Postdoctoral fellows, PhD Students & Master student:
Hoa Ombeline, Postdoctoral fellow
Pompili Marco, PhD student
Benabdallah Nadia, PhD student
Bochereau Ariane, PhD student
Boucly Celine, PhD student
Brito Raphaël, PhD student
Mena Orostica Wilson-Andres, PhD student
Simula Sara, Master student
Mathevet Théo, Master student

Technical staff:
Zaoui Mohamed, IEHC CNRS
Todorova Ralitsa, CDD IR