After graduating in Cognitive Neuroscience from the Aix-Marseille Provence University, I obtained an MS in Neuroscience (2001) and a PhD in Developmental Neurobiology in 2005 from the University Claude Bernard in Lyon. For my postdoctoral work, I turned to my long-term passion which is to understand the function of sleep. In 2006, I took a post-doctoral position in the laboratory of Marcos Frank at the University of Pennsylvania (USA) where I started to explore the link between sleep and brain plasticity mechanisms during development. My research there focused on the role of mRNA translation in sleep-dependent brain plasticity enhancement. In 2010, I joined the group of Matthew Larkum at the Charité-Universtätsmedizin Berlin where I developed an in vivo calcium imaging technique to investigate the influence of sleep and sleep oscillations on activity in neuronal dendrites during natural sleep in rodents. This led to the discovery that calcium activity in cortical dendrites is strongly correlated with a specific sleep oscillation important for cognitive function, namely spindles. Since 2016, I am a Lecturer in Sleep & Plasticity at the Surrey Sleep Research Centre (SSRC), Faculty of Health and Medical Sciences, University of Surrey, UK.
My current research focuses on investigating the link between the various aspects of sleep dynamics (e.g. sleep stages and oscillations) and mechanisms of synaptic plasticity. In particular, my work focuses on the regulation of experience-dependent gene expression (molecular mechanism) and dendritic activity (cellular mechanism) in the cortex across the sleep-wake cycle.
Areas of specialism
University roles and responsibilities
- Module coordinator for BMS2048 - Neuroscience, from neurones to behaviour
Affiliations and memberships
Every day our brain disconnects from the environment during sleep and interfering with this process has considerable detrimental effects on our cognitive functions. What is so special about the sleeping brain that helps cognition?
During sleep our brain is far from resting and enters a highly organised pattern of global changes in activity, cycling through periods of large scale network synchronization (i.e. NREM sleep) and desynchronized activity (i.e. dream or REM sleep). Both sleep stages are important for maintaining proper cognition but the underlying physiology is not well understood.
My main research interest is to understand the link between sleep stages and synaptic plasticity - the fundamental mechanism that allows us to adapt and change communication between neurons in response to experience. We take a multidisciplinary experimental approach, including electrophysiology, molecular, in vivo optical imaging methods and behavioural manipulations in the rodent model.
Projects that we currently pursue include:
- The influence of sleep and experience on translation regulation
- The regulation of cortical dendritic activity by sleep and experience
- The physiology and role of sleep spindles
Prof Matthew Larkum - Humboldt Universität zu Berlin, Germany
Dr Jini Naidoo - University of Pennsylvania, USA
Prof André Gerber - University of Surrey, UK
Postgraduate research supervision
José Lucas Santos (sleep translatome)
BMS2048: Neuroscience, from Neurons to Behaviour (Coordinator)
BMS3064: Neuroscience, from Molecules to Mind
Health and Disease, Neural Plasticity 2016 8103439 Hindawi Publishing Corporation
spindle-rich oscillations during sleep in rodents, Nature Communications 8 684 Nature Publishing Group
(EEG) rhythms are linked to memory consolidation is poorly understood.
Calcium activity in dendrites is known to be necessary for structural plasticity changes, but
this has never been carefully examined during sleep. Here, we report that calcium activity in
populations of neocortical dendrites is increased and synchronised during oscillations in the
spindle range in naturally sleeping rodents. Remarkably, the same relationship is not found in
cell bodies of the same neurons and throughout the cortical column. Spindles during sleep
have been suggested to be important for brain development and plasticity. Our results
provide evidence for a physiological link of spindles in the cortex specific to dendrites, the
main site of synaptic plasticity.
consolidation. Neural events during post-learning sleep share key features with both
early and late stages of memory consolidation. For example, recent studies have shown
neuronal changes during post-learning sleep which reflect early synaptic changes
associated with consolidation, including activation of shared intracellular pathways and
modifications of synaptic strength. Sleep may also play a role in later stages of
consolidation involving propagation of memory traces throughout the brain. However,
to date the precise molecular and physiological aspects of sleep required for this process
remain unknown. The behavioural effects of sleep may be mediated by the large-scale,
global changes in neuronal activity, synchrony and intracellular communication that
accompany this vigilance state, or by synapse-specific ?replay? of activity patterns
associated with prior learning.
Consolidates Cortical Plasticity In Vivo, Current Biology 22 pp. 676-682 Elsevier
but the precise cellular mechanisms mediating this process
are unknown . De novo cortical protein synthesis is one
possible mechanism. In support of this hypothesis, sleep
is associated with increased brain protein synthesis [2, 3]
and transcription of messenger RNAs (mRNAs) involved in
protein synthesis regulation [4, 5]. Protein synthesis in
turn is critical for memory consolidation and persistent
forms of plasticity in vitro and in vivo [6, 7]. However, it is
unknown whether cortical protein synthesis in sleep serves
similar functions. We investigated the role of protein
synthesis in the sleep-dependent consolidation of a classic
form of cortical plasticity in vivo (ocular dominance plasticity,
ODP; [8, 9]) in the cat visual cortex. We show that
intracortical inhibition of mammalian target of rapamycin
(mTOR)-dependent protein synthesis during sleep abolishes
consolidation but has no effect on plasticity induced
during wakefulness. Sleep also promotes phosphorylation
of protein synthesis regulators (i.e., 4E-BP1 and eEF2) and
the translation (but not transcription) of key plasticity related
mRNAs (ARC and BDNF). These findings show that sleep
promotes cortical mRNA translation. Interruption of this
process has functional consequences, because it abolishes
the consolidation of experience in the cortex.
of Thalamic Neurons by Controlling
Axon Responsiveness to Intermediate Target Cues, Neuron 39 (3) pp. 439-452 Elsevier
of Thalamocortical Projections
Are Controlled by ephrin/Eph Genes, Neuron 39 (3) pp. 453-465 Elsevier
by Proneural Genes in the Developing Telencephalon, PLoS ONE 7 (11) e48675
parental origin. Several imprinted genes are implicated in neurodevelopmental brain disorders, such as autism, Angelman,
and Prader-Willi syndromes. However, how expression of these imprinted genes is regulated during neural development is
poorly understood. Here, using single and double KO animals for the transcription factors Neurogenin2 (Ngn2) and Achaetescute
homolog 1 (Ascl1), we found that the expression of a specific subset of imprinted genes is controlled by these
proneural genes. Using in situ hybridization and quantitative PCR, we determined that five imprinted transcripts situated at
the Dlk1-Gtl2 locus (Dlk1, Gtl2, Mirg, Rian, Rtl1) are upregulated in the dorsal telencephalon of Ngn2 KO mice. This suggests
that Ngn2 influences the expression of the entire Dlk1-Gtl2 locus, independently of the parental origin of the transcripts.
Interestingly 14 other imprinted genes situated at other imprinted loci were not affected by the loss of Ngn2. Finally, using
Ngn2/Ascl1 double KO mice, we show that the upregulation of genes at the Dlk1-Gtl2 locus in Ngn2 KO animals requires
a functional copy of Ascl1. Our data suggest a complex interplay between proneural genes in the developing forebrain that
control the level of expression at the imprinted Dlk1-Gtl2 locus (but not of other imprinted genes). This raises the possibility
that the transcripts of this selective locus participate in the biological effects of proneural genes in the developing
Recent findings indicate that certain classes of hypnotics that target GABAA receptors impair sleep-dependent brain plasticity. However, the effects of hypnotics acting at monoamine receptors (e.g., the antidepressant trazodone) on this process are unknown. We therefore assessed the effects of commonly-prescribed medications for the treatment of insomnia (trazodone and the non-benzodiazepine GABAA receptor agonists zaleplon and eszopiclone) in a canonical model of sleep-dependent, in vivo synaptic plasticity in the primary visual cortex (V1) known as ocular dominance plasticity.
After a 6-h baseline period of sleep/wake polysomnographic recording, cats underwent 6 h of continuous waking combined with monocular deprivation (MD) to trigger synaptic remodeling. Cats subsequently received an i.p. injection of either vehicle, trazodone (10 mg/kg), zaleplon (10 mg/kg), or eszopiclone (1?10 mg/kg), and were allowed an 8-h period of post-MD sleep before ocular dominance plasticity was assessed. We found that while zaleplon and eszopiclone had profound effects on sleeping cortical electroencephalographic (EEG) activity, only trazodone (which did not alter EEG activity) significantly impaired sleep-dependent consolidation of ocular dominance plasticity. This was associated with deficits in both the normal depression of V1 neuronal responses to deprived-eye stimulation, and potentiation of responses to non-deprived eye stimulation, which accompany ocular dominance plasticity.
Taken together, our data suggest that the monoamine receptors targeted by trazodone play an important role in sleep-dependent consolidation of synaptic plasticity. They also demonstrate that changes in sleep architecture are not necessarily reliable predictors of how hypnotics affect sleep-dependent neural functions.
and -independent pathways, The EMBO Journal 23 (14) pp. 2892-2902 EMBO Press
cortical layers according to their birthdate, have diverse
morphologies, axonal projections and molecular profiles,
yet they share a common cortical regional identity and
glutamatergic neurotransmission phenotype. Here we demonstrate
that distinct genetic programs operate at different
stages of corticogenesis to specify the properties shared
by all neocortical neurons. Ngn1 and Ngn2 are required to
specify the cortical (regional), glutamatergic (neurotransmitter)
and laminar (temporal) characters of early-born
(lower-layer) neurons, while simultaneously repressing an
alternative subcortical, GABAergic neuronal phenotype.
Subsequently, later-born (upper-layer) cortical neurons
are specified in an Ngn-independent manner, requiring
instead the synergistic activities of Pax6 and Tlx, which
also control a binary choice between cortical/glutamatergic
and subcortical/GABAergic fates. Our study thus reveals an
unanticipated heterogeneity in the genetic mechanisms
specifying the identity of neocortical projection neurons.
Plasticity, Sleep 31 (10) pp. 1381-1391 Oxford University Press
The effects of hypnotics on sleep-dependent brain
plasticity are unknown. We have shown that sleep enhances a canonical
model of in vivo cortical plasticity, known as ocular dominance
plasticity (ODP). We investigated the effects of 3 different classes of
hypnotics on ODP.
Polysomnographic recordings were performed during the entire
experiment (20 h). After a baseline sleep/wake recording (6 h), cats
received 6 h of monocular deprivation (MD) followed by an i.p. injection
of triazolam (1-10 mg/kg i.p.), zolpidem (10 mg/kg i.p.), ramelteon
(0.1-1 mg/kg i.p.), or vehicle (DMSO i.p.). They were then allowed to
sleep ad lib for 8 h, after which they were prepared for optical imaging
of intrinsic cortical signals and single-unit electrophysiology.
Setting: Basic neurophysiology laboratory
Patients or Participants:
Cats (male and female) in the critical period
of visual development (postnatal days 28-41)
Measurements and Results:
Zolpidem reduced cortical plasticity by
~50% as assessed with optical imaging of intrinsic cortical signals.
This was not due to abnormal sleep architecture because triazolam,
which perturbed sleep architecture and sleep EEGs more profoundly
than zolpidem, had no effect on plasticity. Ramelteon minimally altered
sleep and had no effect on ODP.
Our findings demonstrate that alterations in sleep architecture
do not necessarily lead to impairments in sleep function.
Conversely, hypnotics that produce more ?physiological? sleep based
on polysomnography may impair critical brain processes, depending
on their pharmacology.
memory in both humans and animals. While the underlying mechanisms are not fully understood, it has been
suggested that brain activity during sleep modulates neuronal communication through synaptic plasticity. These
insights were mostly gained using electrophysiology to monitor ongoing large scale and single cell activity.
While these efforts were instrumental in the characterisation of important network and cellular activity during
sleep, several aspects underlying cognition are beyond the reach of this technology. Neuronal circuit activity is
dynamically regulated via the precise interaction of different neuronal and non-neuronal cell types and relies on
subtle modifications of individual synapses. In contrast to established electrophysiological approaches, recent
advances in imaging techniques, mainly applied in rodents, provide unprecedented access to these aspects of
neuronal function in vivo.
In this review, we describe various techniques currently available for in vivo brain imaging, from single
synapse to large scale network activity. We discuss the advantages and limitations of these approaches in the
context of sleep research and describe which particular aspects related to cognition lend themselves to this kind
of investigation. Finally, we review the few studies that used in vivo imaging in rodents to investigate the
sleeping brain and discuss how the results have already significantly contributed to a better understanding on
the complex relation between sleep and plasticity across development and adulthood.
of Synaptic Plasticity Across Brain
States, Frontiers in Neuroscience Frontiers Media
how these different brain states work in concert to create long-lasting changes in brain
circuitry is unclear. Considering that wakefulness and sleep are profoundly different
brain states on multiple levels (e.g., cellular, molecular and network activation), it is
unlikely that they operate exactly the same way. Rather it is probable that they engage
different, but coordinated, mechanisms. In this article we discuss how plasticity may be
divided across the sleep?wake cycle, and how synaptic changes in each brain state are
linked. Our working model proposes that waking experience triggers short-lived synaptic
events that are necessary for transient plastic changes and mark (i.e., ?prime?) circuits
and synapses for further processing in sleep. During sleep, synaptic protein synthesis
at primed synapses leads to structural changes necessary for long-term information