Ultra-thin rigid endoscope: Two-photon imaging through a graded-index multi-mode fiber

Rigid endoscopes like graded-index (GRIN) lenses are known tools in biological imaging, but it is conceptually difficult to miniaturize them. In this letter, we demonstrate an ultra-thin rigid endoscope with a diameter of only 125 microns. In addition, we identify a domain where two-photon endoscopic imaging with fs-pulse excitation is possible. We validate the ultra-thin rigid endoscope consisting of a few cm of graded-index multi-mode fiber by using it to acquire optically sectioned two-photon fluorescence endoscopic images of three-dimensional samples.Comment: 17 pages, 15 figures, submitted to Opt. Expres

Paradoxical anti-epileptic effects of a GluR5 agonist of kainate receptors.

International audienceKainate generates in adult hippocampal neurons a seizure but also a massive excitation of interneurons and a dramatic increase of the inhibitory drive that impinges on principal cells. This "overinhibition" is largely mediated by GluR5-containing kainate receptors that are enriched on interneurons. Here, using the neonatal intact hippocampus in vitro and the triple chamber, we first show that this mechanism is fully operative in neonatal neurons. We then report that application to one hippocampus of (RS)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid-a relatively selective agonist of GluR5 containing kainate receptors-depresses the propagation of seizure generated in the opposite hippocampus by a convulsive agent. We conclude that the selective excitation of interneurons by GluR5-containing kainate receptor agonists opens a new therapeutic approach for the epilepsies

A Parturition-Associated Nonsynaptic Coherent Activity Pattern in the Developing Hippocampus

SummaryCorrelated neuronal activity is instrumental in the formation of networks, but its emergence during maturation is poorly understood. We have used multibeam two-photon calcium microscopy combined with targeted electrophysiological recordings in order to determine the development of population coherence from embryonic to postnatal stages in the hippocampus. At embryonic stages (E16–E19), synchronized activity is absent, and neurons are intrinsically active and generate L-type channel-mediated calcium spikes. At birth, small cell assemblies coupled by gap junctions spontaneously generate synchronous nonsynaptic calcium plateaus associated to recurrent burst discharges. The emergence of coherent calcium plateaus at birth is controlled by oxytocin, a maternal hormone initiating labour, and progressively shut down a few days later by the synapse-driven giant depolarizing potentials (GDPs) that synchronize the entire network. Therefore, in the developing hippocampus, delivery is an important signal that triggers the first coherent activity pattern, which is silenced by the emergence of synaptic transmission

GABAergic inhibition shapes interictal dynamics in awake epileptic mice

International audienceEpilepsy is characterized by recurrent seizures and brief, synchronous bursts called interictal spikes that are present in-between seizures and observed as transient events in EEG signals. While GABAergic transmission is known to play an important role in shaping healthy brain activity, the role of inhibition in these pathological epileptic dynamics remains unclear. Examining the microcircuits that participate in interictal spikes is thus an important first step towards addressing this issue, as the function of these transient synchronizations in either promoting or prohibiting seizures is currently under debate. To identify the microcircuits recruited in spontaneous interictal spikes in the absence of any proconvulsive drug or anaesthetic agent, we combine a chronic model of epilepsy with in vivo two-photon calcium imaging and multiunit extracellular recordings to map cellular recruitment within large populations of CA1 neurons in mice free to run on a self-paced treadmill. We show that GABAergic neurons, as opposed to their glutamatergic counterparts, are preferentially recruited during spontaneous interictal activity in the CA1 region of the epileptic mouse hippocampus. Although the specific cellular dynamics of interictal spikes are found to be highly variable, they are consistently associated with the activation of GABAergic neurons, resulting in a perisomatic inhibitory restraint that reduces neuronal spiking in the principal cell layer. Given the role of GABAergic neurons in shaping brain activity during normal cognitive function, their aberrant unbalanced recruitment during these transient events could have important downstream effects with clinical implications

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Operational hub cells: a morpho-physiologically diverse class of GABAergic neurons united by a common function

International audienceGABAergic microcircuits structure the activation of neuronal ensembles that support most cortical computations. Because of the heterogeneous nature of the GABAergic cell community, a full understanding of structure–function relationships in these microcircuits may be hampered by a reductionist approach that consists of classifying them according to an exhaustive collection of parameters. It therefore could be beneficial to our understanding of these complex cells to also consider other approaches. Thus, graph theory has recently taught us that biological networks often include hub nodes that are essential for information flow, and ensuing experimental evidence has demonstrated the existence of ‘operational’ hub neurons. So far, only GABAergic neurons have been identified as ‘operational hubs’, further emphasizing their critical function in controlling cortical network dynamics

The maturation of cortical interneuron diversity: how multiple developmental journeys shape the emergence of proper network function

International audienceIf the classical functional attribute of cortical GABAergic interneurons is to mediate synaptic inhibition in the adult cortex, it is becoming evident that their major task is instead to shape the spatio-temporal dynamics of the network oscillations that support most brain functions. This complex function involves a division of labour between morpho-physiologically diverse interneuron subtypes. Both the central network function and the bewildering heterogeneity of the interneuron population are especially emphasized during cortical development: at early postnatal stages, a single GABAergic neuron can efficiently pace the activity of hundreds of other cells, whereas some interneuron subtypes are still poorly developed. Given the role of coherent activity in brain development, this confers to GABAergic interneurons a major role in the proper maturation of cortical networks

Step by step: cells with multiple functions in cortical circuit assembly

International audienc

Structure-fonction des patrons d'activité séquentiels des réseaux corticaux au cours du développement postnatal chez le rongeur

Une des caractéristiques remarquables des structures cérébrales en développement est leur propension à exprimer des patrons d activité neuronale corrélée spontanés (Pour revue : Blankenship and Feller, 2010). Au cours de la première semaine de vie postnatale chez le rongeur, se succèdent des patrons aux caractéristiques spatio-temporelles différentes, portés par des mécanismes cellulaires différents. On identifie donc différents stades de développement d activité neuronale corrélée constituant une séquence. Notre hypothèse est que cette séquence ne reflète pas uniquement la maturation séquentielle des propriétés intrinsèques et synaptiques des neurones individuels, mais qu elle participe directement aux processus de maturation. Nous avons testé cette hypothèse au cours de cette thèse, à partir de l étude de la séquence des patrons d activité neuronale corrélée de l hippocampe et du néocortex pendant la première semaine de vie postnatale chezle rongeur. Pour suivre en parallèle la maturation des réseaux et des neurones individuels qui le composent, nous avons suivi la dynamique des activités de réseau en imagerie calcium biphoton et réalisé en parallèle des enregistrement sélectrophysiologiques de neurones ciblés. Nous avons montré que les SPAs, premier patron d activité neuronale corrélée à s exprimer au sein de l hippocampe en développement (Crepel et al., 2007), s expriment également au sein du néocortex immature avec des caractéristiques spatio-temporelles et des mécanismes similaires à ceux rapportés dans l hippocampe. Ceci suggère une implication générale des SPAs dans la maturation des réseaux. Nous avons montré en parallèle que les ENOs, oscillations calciques dominant l activité du néocortex au cours des premiers jours suivant la naissance (Adelsberger et al., 2005; Garaschuk et al., 2000) sont exprimées en même temps que les SPAs. Les ENOs se caractérisent par leur sensibilité à la concentration extracellulaire de glutamate et leur renforcement en condition d anoxie modérée, suggérant que cette forme d activité pourrait en réalité être l expression de conditions pathologiques. Nous avons enfin montré que la séquence de mise enplace des patrons d activité neuronale corrélée du néocortex se terminait avec l apparition des GDPs, décrits pour la première fois ici au sein du néocortex et portés par la transmission GABAergique, dépolarisante à ce stade dudéveloppement (Ben Ari et al., 1989; Crepel et al., 2007; Garaschuk et al., 1998). Se basant sur les similarités apparentes de ces patrons d activités, les ENOs du néocortex étaient considérées comme les homologues néocorticaux des GDPs del hippocampe. Nous avons montré ici que ENOs et GDPs sont deux patrons d activité distincts, caractérisés par des mécanismes et des dynamiques spatio-temporelles différents. Nous avons ensuite étudié le devenir et les propriétés morpho-physiologiques des cellules impliquées dans les SPAs en fonction de la maturation du réseau hippocampique. Dans ce but, nous avons mis au point un protocole d imagerie calciumchronique sur tranches organotypiques d hippocampe, afin de suivre la même population de neurones jour après jour. Nous avons montré que la majorité des cellules SPAs intégraient le réseau synaptique sous-tendant la genèse des GDPs en quelques jours. Parallèlement, nous avons montré que les interneurones GABAergiques impliqués dans les SPAs présentaient des caractéristiques morpho-physiologiques spécifiques telles qu un patron de décharge de potentiels d action immature, une fréquence élevée de courants miniatures postsynaptiques de grande amplitude et la présence de filopodessomatiques, qui les distinguent des interneurones impliqués dans les GDPs.Ces résultats apportent des preuves directes de l existence d une corrélation entre la maturation du réseau et celle des neurones individuels qui le constituent et montrent en particulier comment de profonds changements développementaux concernant les propriétés morpho-physiologiques des interneurones GABAergiques annoncent l émergence des GDPs.1Developing cerebral structures generate spontaneous synchronous neuronal activity patterns which are sequencially express during the first postnatal week in rodent. Does this sequence of activity pattens participate in process of neuronal network maturation ? We follow the dynamic of network activity using biphoton calcium imaging and electrophysiological recordings of targeted neurons. We describe the sequence of activity pattern in developing neocortex the we show that the first activity pattern of this sequence, the SPA, common to hippocampus and neocortex, has specific morpho-physiological properties, different from the ones of the next activity pattern : the GDPs. Moreover, the majority of SPA cells integrate the synaptic network of GDPs in few days. These results bring direct evidences that sequential activity patterns during development participate in the neuronal network maturationAIX-MARSEILLE2-Bib.electronique (130559901) / SudocSudocFranceF