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June 2011 - December 2014
Publications
Publications (32)
Huntington's disease (HD) is a neurodegenerative disorder that presents motor, cognitive and psychiatric symptoms as it progresses. Prior to motor symptoms onset, alterations and dysfunctions in the corticostriatal projections have been described along with cognitive deficits, but the sequence of early defects of brain circuits is largely unknown....
The dorsomedial striatum (DMS) is an associative node involved in the adaptation of ongoing actions to the environmental context and in the initial formation of motor sequences. In early associative or motor learning phases, DMS activity shows a global decrease in neuron firing, eventually giving rise to a select group of active cells, whose number...
Motor skill learning requires the activity of the dorsal striatum, with a differential global implication of the dorsomedial and dorsolateral territories. We investigate here whether and how specific striatal neurons encode the acquisition and consolidation of a motor skill. Using ex vivo two-photon calcium imaging after rotarod training, we report...
Striatum processes a wide range of functions including goal-directed behavior and habit formation, respectively encoded by the dorsomedial striatum (DMS) and dorsolateral striatum (DLS). GABAergic feedforward inhibition is known to control the integration of cortical information by striatal projection neurons (SPNs). Here we questioned whether this...
Huntington's disease (HD), a devastating neurodegenerative disorder, strongly affects the corticostriatal network, but the contribution of pre- and postsynaptic neurons in the first phases of disease is unclear due to difficulties performing early subcellular investigations in vivo. Here, we have developed an on-a-chip approach to reconstitute an H...
Activity-dependent long-term potentiation (LTP) and depression (LTD) of synaptic strength underlie multiple forms of learning and memory. Spike-timing-dependent plasticity (STDP) has been described as a Hebbian synaptic learning rule that could account for experience-dependent changes in neural networks, but little is known about whether and how ST...
Synaptic plasticity, a main substrate for learning and memory, is commonly assessed with prolonged stimulations. Since learning can arise from few or even a single trial, synaptic strength is expected to adapt rapidly. However, it remains elusive whether synaptic plasticity occurs in response to limited event occurrences. To answer this question, w...
The spike-timing-dependent plasticity (STDP), a synaptic learning rule for encoding learning and memory, relies on relative timing of neuronal activity on either side of the synapse. GABAergic signaling has been shown to control neuronal excitability and consequently the spike timing, but whether GABAergic circuits rule the STDP remained unknown. H...
Neocortical GABAergic interneurons have important roles in the normal and pathological states of the circuit. Recent work has revealed that somatostatin-positive (SOM) and parvalbumin-positive (PV) interneurons connect promiscuously to pyramidal cells (PCs). We investigated whether Peters' rule, that is, the spatial overlap of axons and dendrites,...
Although inhibition plays a major role in the function of the mammalian neocortex, the circuit connectivity of GABAergic interneurons has remained poorly understood. The authors review recent studies of the connections made to and from interneurons, highlighting the overarching principle of a high density of unspecific connections in inhibitory con...
The astrocytes, active elements of the tripartite synapse, remove most of the neurotransmitter that spills over the synaptic cleft. Neurotransmitter uptake operated by astrocytes contributes to the strength and timing of synaptic inputs. The striatum, the main input nucleus of basal ganglia, extracts pertinent cortical signals from the background n...
Introduction:
For the study of neural circuits, it would be ideal to be able to discern in a living preparation the interconnections among neurons. Working toward that aim, we have developed a method, using two-photon uncaging of glutamate in brain slices, by which we can detect neurons that are presynaptic to any particular cell. The method, desc...
The connectivity diagram of neocortical circuits is still unknown, and there are conflicting data as to whether cortical neurons are wired specifically or not. To investigate the basic structure of cortical microcircuits, we use a two-photon photostimulation technique that enables the systematic mapping of synaptic connections with single-cell reso...
Corticostriatal projections constitute the main input to the basal ganglia, an ensemble of interconnected subcortical nuclei involved in procedural learning. Thus, long-term plasticity at corticostriatal synapses would provide a basic mechanism for the function of basal ganglia in learning and memory. We had previously reported the existence of a c...
The striatum is the major input nucleus of basal ganglia, an ensemble of interconnected sub-cortical nuclei associated with fundamental processes of action-selection and procedural learning and memory. The striatum receives afferents from the cerebral cortex and the thalamus. In turn, it relays the integrated information towards the basal ganglia o...
Deciphering the circuitry of the neocortex requires knowledge of its components, making a systematic classification of neocortical neurons necessary. GABAergic interneurons contribute most of the morphological, electrophysiological and molecular diversity of the cortex, yet interneuron subtypes are still not well defined. To quantitatively identify...
We have developed a spatial light modulator (SLM) based microscope that uses diffraction to shape the incoming two-photon laser source to any arbitrary light pattern. This allows the simultaneous imaging or photostimulation of different regions of a sample with three-dimensional precision at high frame rates. Additionally, we have combined this mic...
Pharmacology of plasticity induced by post-pre and pre-post sequences. (A) For post-pre sequences (−50≤Δt≤0 ms), with AP5, sdLTP was no longer observed while sdLTD could still be induced (−14.7±10.3%, n = 6). Conversely, with AM251, we did not observe significant sdLTD while sdLTP still occurred (+15.5±14.3%, n = 5). (B) For pre-post sequences (0≤Δ...
Characterization of SDDP. The magnitudes of long-term synaptic efficacy changes were plotted against EPSC rise time in control (A), EPSC latency in control (B), EPSC amplitude in control (C), RMP (D) and input resistance (E). No significant correlation was found between these parameters and the magnitude of long-term synaptic efficacy changes induc...
We describe neurobiological applications of RuBi-Glutamate, a novel caged-glutamate compound based on ruthenium photochemistry. RuBi-Glutamate can be excited with visible wavelengths and releases glutamate after one- or two-photon excitation. It has high quantum efficiency and can be used at low concentrations, partly avoiding the blockade of GABAe...
Corticostriatal projections constitute the major inputs to basal ganglia, an ensemble of sub-cortical nuclei involved in the learning of cognitive-motor sequences in response to environmental stimuli. Besides striatal output neurons (medium-sized spiny neurons, MSNs) in charge of the detection of cortical activity, three main classes of interneuron...
Action potentials are thought to be determinant for the induction of long-term synaptic plasticity, the cellular basis of learning and memory. However, neuronal activity does not lead systematically to an action potential but also, in many cases, to synaptic depolarizing subthreshold events. This is particularly exemplified in corticostriatal infor...
Striatum, the main input nucleus of basal ganglia, is involved in the learning of cognitive and motor sequences in response to environmental stimuli. Striatal output neurons (medium spiny neurons, MSNs) integrate cortical activity and the two main classes of interneurons (GABAergic and cholinergic interneurons) tightly regulate the corticostriatal...
Le striatum a pour rôle de sélectionner et d'intégrer les informations provenant du cortex et ainsi construire et transmettre une réponse adaptée aux stimuli environnementaux. Nous avons caractérisé les propriétés électrophysiologiques des différents neurones du striatum (neurones de sortie, NETM, et interneurones) dans des conditions normales, et...
The striatum, the main input nucleus of basal ganglia, receives a massive innervation from the entire cerebral cortex and is in charge of the detection of behaviorally relevant signals. In turn, via its projections to the output nuclei of basal ganglia, the striatum contributes to the organization of appropriate compartmental responses. Substantia...
Corticostriatal projections originate from the entire cerebral cortex and provide the major source of glutamatergic inputs to the basal ganglia. Despite the importance of corticostriatal connections in sensorimotor learning and cognitive functions, plasticity forms at these synapses remain strongly debated. Using a corticostriatal slice preserving...
Pituitary growth hormone (GH)-secreting cells regulate growth and metabolism in animals and humans. To secrete highly ordered GH pulses (up to 1,000-fold rise in hormone levels in vivo), the pituitary GH cell population needs to mount coordinated responses to GH secretagogues, yet GH cells display an apparently heterogeneous scattered distribution...