Activity dependent feedback inhibition may maintain head direction signals in mouse presubiculum

Orientation in space is represented in specialized brain circuits. Persistent head direction signals are transmitted from anterior thalamus to the presubiculum, but the identity of the presubicular target neurons, their connectivity and function in local microcircuits are unknown. Here, we examine how thalamic afferents recruit presubicular principal neurons and Martinotti interneurons, and the ensuing synaptic interactions between these cells. Pyramidal neuron activation of Martinotti cells in superficial layers is strongly facilitating such that high-frequency head directional stimulation efficiently unmutes synaptic excitation. Martinotti-cell feedback plays a dual role: precisely timed spikes may not inhibit the firing of in-tune head direction cells, while exerting lateral inhibition. Autonomous attractor dynamics emerge from a modelled network implementing wiring motifs and timing sensitive synaptic interactions in the pyramidal - Martinotti-cell feedback loop. This inhibitory microcircuit is therefore tuned to refine and maintain head direction information in the presubiculum

Multisensory gaze stabilization in response to subchronic alteration of vestibular type I hair cells

The functional complementarity of the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) allows for optimal combined gaze stabilization responses (CGR) in light. While sensory substitution has been reported following complete vestibular loss, the capacity of the central vestibular system to compensate for partial peripheral vestibular loss remains to be determined. Here, we first demonstrate the efficacy of a 6-week subchronic ototoxic protocol in inducing transient and partial vestibular loss which equally affects the canal- and otolith-dependent VORs. Immunostaining of hair cells in the vestibular sensory epithelia revealed that organ-specific alteration of type I, but not type II, hair cells correlates with functional impairments. The decrease in VOR performance is paralleled with an increase in the gain of the OKR occurring in a specific range of frequencies where VOR normally dominates gaze stabilization, compatible with a sensory substitution process. Comparison of unimodal OKR or VOR versus bimodal CGR revealed that visuo-vestibular interactions remain reduced despite a significant recovery in the VOR. Modeling and sweep-based analysis revealed that the differential capacity to optimally combine OKR and VOR correlates with the reproducibility of the VOR responses. Overall, these results shed light on the multisensory reweighting occurring in pathologies with fluctuating peripheral vestibular malfunction

Increasing the effectiveness of intracerebral injections in adult and neonatal mice: a neurosurgical point of view

International audienceIntracerebral injections of tracers or viral constructs in rodents are now commonly used in the neurosciences and must be executed perfectly. The purpose of this article is to update existing protocols for intracerebral injections in adult and neonatal mice. Our procedure for stereotaxic injections in adult mice allows the investigator to improve the effectiveness and safety, and save time. Furthermore, for the first time, we describe a two-handed procedure for intracerebral injections in neonatal mice that can be performed by a single operator in a very short time. Our technique using the stereotaxic arm allows a higher precision than freehand techniques previously described. Stereotaxic injections in adult mice can be performed in 20 min and have >90% efficacy in targeting the injection site. Injections in neonatal mice can be performed in 5 min. Efficacy depends on the difficulty of precisely localizing the injection sites, due to the small size of the animal. We describe an innovative, effortless, and reproducible surgical protocol for intracerebral injections in adult and neonatal mice

FACTEURS CONTROLANT L'EXCITABILITE DANS LES NEURONES DE L'HIPPOCAMPE

LA TRANSMISSION DE L'ACTIVITE NERVEUSE AU LONG DE CHAINES DE PLUSIEURS NEURONES DEPEND DE LA FACILITE AVEC LAQUELLE UN POTENTIEL POST-SYNAPTIQUE EXCITATEUR PEUT FAIRE DECHARGER UN NEURONE POST-SYNAPTIQUE. LA DIFFERENCE ENTRE LE POTENTIEL DE REPOS ET LE SEUIL DE DECHARGE EST DONC UN DETERMINANT CRUCIAL DU FONCTIONNEMENT DU RESEAU HIPPOCAMPIQUE. DANS CETTE THESE, J'AI EMPLOYE UNE TECHNIQUE INGENIEUSE DE MESURER LE POTENTIEL TRANSMEMBRANAIRE EN MODE CELLULE-ATTACHEE, EN UTILISANT DES COURANTS POTASSIQUES VOLTAGE-DEPENDANTS A TRAVERS LE PATCH. J'AI AINSI DETERMINE LE POTENTIEL DE REPOS DES INTERNEURONES ET DES CELLULES PYRAMIDALES DE LA REGION CA1, SUR DES TRANCHES D'HIPPOCAMPE DE RAT. LE CARACTERE NON-INVASIVE DE CETTE TECHNIQUE CONVIENT PARTICULIEREMENT A L'ETUDE DE L'EFFET DE GABA, ET UNE ACTION DIFFERENTIELLE SELON LE TYPE DE RECEPTEUR ACTIVE ET SELON L'AGE DES ANIMAUX A ETE MIS EN EVIDENCE. LE SEUIL DE DECHARGE ETAIT DETERMINE EN SUIVANT LE POTENTIEL MEMBRANAIRE EN MODE CELLULE-ATTACHEE, PENDANT QU'UNE AUGMENTATION DE K + E X T DEPOLARISE PROGRESSIVEMENT LE NEURONE. J'AI COMPARE CES RESULTATS AVEC LE SEUIL QU'ON MESURE DANS DES EXPERIENCES CONDUITES EN CELLULE-ENTIERE. L'INTENSITE DU COURANT INJECTE NECESSAIRE POUR FAIRE DECHARGER UN NEURONE DECROIT DE FACON EXPONENTIELLE AVEC LA DUREE D'UNE STIMULATION, PENDANT QUE LE SEUIL EN TERME DE VOLTAGE VARIE PEU AVEC LA VITESSE DE POLARISATION DE LA MEMBRANE. J'AI DEMONTRE QU'IL Y A UNE FORTE INACTIVATION DES CANAUX SODIQUES ET POTASSIQUES PRES DU SEUIL, ET QUE LE PASSAGE A L'ETAT INACTIVE SE FAIT RAPIDEMENT. ENSUITE J'AI ETUDIE LE COUPLAGE ENTRE UN PPSE ET LE POTENTIEL D'ACTION QU'IL INITIE. DANS LES CELLULES PYRAMIDALES, LES POTENTIELS D'ACTION SONT GENERES AVEC DES LATENCES VARIABLES DEPUIS DES PPSE AMPLIFIES ET PROLONGES PAR DES COURANTS SODIQUES. DANS LES INTERNEURONES, LA FENETRE TEMPORELLE POUR L'INITIATION DES POTENTIELS D'ACTIONS EST ETROITE, DU A UNE ACTIVATION IMPORTANTE DES COURANTS POTASSIQUES.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Neuron–Oligodendrocyte Communication in Myelination of Cortical GABAergic Cells

International audienceAxonal myelination by oligodendrocytes increases the speed and reliability of action potential propagation, and so plays a pivotal role in cortical information processing. The extent and profile of myelination vary between different cortical layers and groups of neurons. Two subtypes of cortical GABAergic neurons are myelinated: fast-spiking parvalbumin-expressing cells and somatostatin-containing cells. The expression of pre-nodes on the axon of these inhibitory cells before myelination illuminates communication between oligodendrocytes and neurons. We explore the consequences of myelination for action potential propagation, for patterns of neuronal connectivity and for the expression of behavioral plasticity

In Vivo Intracerebral Stereotaxic Injections for Optogenetic Stimulation of Long-Range Inputs in Mouse Brain Slices

International audienceKnowledge of cell type specific synaptic connectivity is a crucial prerequisite for understanding brain wide neuronal circuits. The functional investigation of long-range connections requires targeted recordings of single neurons combined with the specific stimulation of identified distant inputs. This is often difficult to achieve with conventional, electrical stimulation techniques, because axons from converging upstream brain areas may intermingle in the target region. The stereotaxic targeting of a specific brain region for virus-mediated expression of light sensitive ion channels allows to selectively stimulate axons coming from that region with light. Intracerebral stereotaxic injections can be used in well-delimited structures, such as the anterodorsal thalamic nuclei, and also in other subcortical or cortical areas throughout the brain. Here we describe a set of techniques for precise stereotaxic injection of viral vectors expressing channelrhodopsin in the anterodorsal thalamus, followed by photostimulation of their axon terminals in hippocampal slices. In combination with whole-cell patch clamp recording from a postsynaptically connected presubicular neuron, photostimulation of thalamic axons allows the detection of functional synaptic connections, their pharmacological characterization, and the evaluation of their strength in the brain slice preparation. We demonstrate that axons originating in the anterodorsal thalamus ramify densely in presubicular layers 1 and 3. The photostimulation of Chronos expressing thalamic axon terminals in presubiculum initiates short latency postsynaptic responses in a presubicular layer3 neuron, indicating a monosynaptic connection. In addition, biocytin filling of the recorded neuron and posthoc revelation confirms the layer localization and pyramidal morphology of the postsynaptic neuron. Taken together, the optogenetic stimulation of long-range inputs in ex vivo brain slices is a useful method to determine the cell-type specific functional connectivity from distant brain regions

Cellular neuroanatomy of rat presubiculum

International audienceThe presubiculum, at the transition from the hippocampus to the cortex, is a key area for spatial information coding but the anatomical and physiological basis of presubicular function remains unclear. Here we correlated the structural and physiological properties of single neurons of the presubiculum in vitro. Unsupervised cluster analysis based on dendritic length and form, soma location, firing pattern and action potential properties allowed us to classify principal neurons into three major cell types. Cluster 1 consisted of a population of small regular spiking principal cells in layers II/III. Cluster 2 contained intrinsically burst firing pyramidal cells of layer IV, with a resting potential close to threshold. Cluster 3 included regular spiking cells of layers V and VI, and could be divided into subgroups 3.1 and 3.2. Cells of cluster 3.1 included pyramidal, multiform and inverted pyramidal cells. Cells of cluster 3.2 contained high-resistance pyramidal neurons that fired readily in response to somatic current injection. These data show that presubicular principal cells generally conform to neurons of the periarchicortex. However, the presence of intrinsic bursting cells in layer IV distinguishes the presubicular cortex from the neighbouring entorhinal cortex. The firing frequency adaptation was very low for principal cells of clusters 1 and 3, a property that should assist the generation of maintained head direction signals in vivo