Gabrielle Devienne

All Publications

• Synaptic cell adhesion moleculeCdh6identifies a class of sensory neurons with novel functions in colonic motility. bioRxiv : the preprint server for biology Gomez-Frittelli, J., Devienne, G., Travis, L., Kyloh, M. A., Duan, X., Hibberd, T. J., Spencer, N. J., Huguenard, J. R., Kaltschmidt, J. A. 2024

  Abstract

  Intrinsic sensory neurons are an essential part of the enteric nervous system (ENS) and play a crucial role in gastrointestinal tract motility and digestion. Neuronal subtypes in the ENS have been distinguished by their electrophysiological properties, morphology, and expression of characteristic markers, notably neurotransmitters and neuropeptides. Here we investigated synaptic cell adhesion molecules as novel cell type markers in the ENS. Our work identifies two Type II classic cadherins, Cdh6 and Cdh8, specific to sensory neurons in the mouse colon. We show that Cdh6+ neurons demonstrate all other distinguishing classifications of enteric sensory neurons including marker expression of Calcb and Nmu, Dogiel type II morphology and AH-type electrophysiology and I H current. Optogenetic activation of Cdh6+ sensory neurons in distal colon evokes retrograde colonic motor complexes (CMCs), while pharmacologic blockade of rhythmicity-associated current I H disrupts the spontaneous generation of CMCs. These findings provide the first demonstration of selective activation of a single neurochemical and functional class of enteric neurons, and demonstrate a functional and critical role for sensory neurons in the generation of CMCs.

  View details for DOI 10.1101/2024.08.06.606748

  View details for PubMedID 39149241

• Reuniens thalamus recruits recurrent excitation in medial prefrontal cortex. bioRxiv : the preprint server for biology Vantomme, G., Devienne, G., Hull, J. M., Huguenard, J. R. 2024

  Abstract

  Medial prefrontal cortex (mPFC) and hippocampus are critical for memory retrieval, decision making and emotional regulation. While ventral CA1 (vCA1) shows direct and reciprocal connections with mPFC, dorsal CA1 (dCA1) forms indirect pathways to mPFC, notably via the thalamic Reuniens nucleus (Re). Neuroanatomical tracing has documented structural connectivity of this indirect pathway through Re however, its functional operation is largely unexplored. Here we used in vivo and in vitro electrophysiology along with optogenetics to address this question. Whole-cell patch-clamp recordings in acute mouse brain slices revealed both monosynaptic excitatory responses and disynaptic feedforward inhibition for both Re-mPFC and Re-dCA1 pathways. However, we also identified a novel biphasic excitation of mPFC by Re, but not dCA1. These early monosynaptic and late recurrent components are in marked contrast to the primarily feedforward inhibition characteristic of thalamic inputs to neocortex. Local field potential recordings in mPFC brain slices revealed that this biphasic excitation propagates throughout all cortical lamina, with the late excitation specifically enhanced by GABAAR blockade. In vivo Neuropixels recordings in head-fixed awake mice revealed a similar biphasic excitation of mPFC units by Re activation. In summary, Re output produces recurrent feed-forward excitation within mPFC suggesting a potent amplification system in the Re-mPFC network. This may facilitate amplification of dCA1->mPFC signals for which Re acts as the primary conduit, as there is little direct connectivity. In addition, the capacity of mPFC neurons to fire bursts of action potentials in response to Re input suggests that these synapses have a high gain.The interactions between medial prefrontal cortex and hippocampus are crucial for memory formation and retrieval. Yet, it is still poorly understood how the functional connectivity of direct and indirect pathways underlies these functions. This research explores the synaptic connectivity of the indirect pathway through the Reuniens nucleus of the thalamus using electrophysiological recordings and optogenetic manipulations. The study found that Reuniens stimulation recruits recurrent and long-lasting activity in mPFC - a phenomenon not previously recorded. This recurrent activity might create a temporal window ideal for coincidence detection and be an underlying mechanism for memory formation and retrieval.

  View details for DOI 10.1101/2024.05.31.596906

  View details for PubMedID 38854099

  View details for PubMedCentralID PMC11160760

• Author Correction: Precise spatiotemporal control of voltage-gated sodium channels by photocaged saxitoxin. Nature communications Elleman, A. V., Devienne, G., Makinson, C. D., Haynes, A. L., Huguenard, J. R., Du Bois, J. 2022; 13 (1): 2277

  View details for DOI 10.1038/s41467-022-30054-8

  View details for PubMedID 35449160

• Precise spatiotemporal control of voltage-gated sodium channels by photocaged saxitoxin. Nature communications Elleman, A. V., Devienne, G., Makinson, C. D., Haynes, A. L., Huguenard, J. R., Du Bois, J. 2021; 12 (1): 4171

  Abstract

  Here we report the pharmacologic blockade of voltage-gated sodium ion channels (NaVs) by a synthetic saxitoxin derivative affixed to a photocleavable protecting group. We demonstrate that a functionalized saxitoxin (STX-eac) enables exquisite spatiotemporal control of NaVs to interrupt action potentials in dissociated neurons and nerve fiber bundles. The photo-uncaged inhibitor (STX-ea) is a nanomolar potent, reversible binder of NaVs. We use STX-eac to reveal differential susceptibility of myelinated and unmyelinated axons in the corpus callosum to NaV-dependent alterations in action potential propagation, with unmyelinated axons preferentially showing reduced action potential fidelity under conditions of partial NaV block. These results validate STX-eac as a high precision tool for robust photocontrol of neuronal excitability and action potential generation.

  View details for DOI 10.1038/s41467-021-24392-2

  View details for PubMedID 34234116

• Regulation of Perineuronal Nets in the Adult Cortex by the Activity of the Cortical Network JOURNAL OF NEUROSCIENCE Devienne, G., Picaud, S., Cohen, I., Piquet, J., Tricoire, L., Testa, D., Di Nardo, A. A., Rossier, J., Cauli, B., Lambolez, B. 2021; 41 (27): 5779-5790

  Abstract

  Perineuronal net (PNN) accumulation around parvalbumin-expressing (PV) inhibitory interneurons marks the closure of critical periods of high plasticity, whereas PNN removal reinstates juvenile plasticity in the adult cortex. Using targeted chemogenetic in vivo approaches in the adult mouse visual cortex, we found that transient inhibition of PV interneurons, through metabotropic or ionotropic chemogenetic tools, induced PNN regression. Electroencephalographic recordings indicated that inhibition of PV interneurons did not elicit unbalanced network excitation. Likewise, inhibition of local excitatory neurons also induced PNN regression, whereas chemogenetic excitation of either PV or excitatory neurons did not reduce the PNN. We also observed that chemogenetically inhibited PV interneurons exhibited reduced PNN compared to their untransduced neighbors, and confirmed that single PV interneurons express multiple genes enabling individual regulation of their own PNN density. Our results indicate that PNN density is regulated in the adult cortex by local changes of network activity that can be triggered by modulation of PV interneurons. PNN regulation may provide adult cortical circuits with an activity-dependent mechanism to control their local remodeling.SIGNIFICANCE STATEMENTThe perineuronal net is an extracellular matrix, which accumulates around individual parvalbumin-expressing inhibitory neurons during postnatal development, and is seen as a barrier that prevents plasticity of neuronal circuits in the adult cerebral cortex. We found that transiently inhibiting parvalbumin-expressing or excitatory cortical neurons triggers a local decrease of perineuronal net density. Our results indicate that perineuronal nets are regulated in the adult cortex depending on the activity of local microcircuits. These findings uncover an activity-dependent mechanism by which adult cortical circuits may locally control their plasticity.

  View details for DOI 10.1523/JNEUROSCI.0434-21.2021

  View details for Web of Science ID 000672106000002

  View details for PubMedID 34045309

  View details for PubMedCentralID PMC8265812

• Single Cell Multiplex Reverse Transcription Polymerase Chain Reaction After Patch-clamp JOVE-JOURNAL OF VISUALIZED EXPERIMENTS Devienne, G., Le Gac, B., Piquet, J., Cauli, B. 2018

  Abstract

  The cerebral cortex is composed of numerous cell types exhibiting various morphological, physiological, and molecular features. This diversity hampers easy identification and characterization of these cell types, prerequisites to study their specific functions. This article describes the multiplex single cell reverse transcription polymerase chain reaction (RT-PCR) protocol, which allows, after patch-clamp recording in slices, to detect simultaneously the expression of tens of genes in a single cell. This simple method can be implemented with morphological characterization and is widely applicable to determine the phenotypic traits of various cell types and their particular cellular environment, such as in the vicinity of blood vessels. The principle of this protocol is to record a cell with the patch-clamp technique, to harvest and reverse transcribe its cytoplasmic content, and to detect qualitatively the expression of a predefined set of genes by multiplex PCR. It requires a careful design of PCR primers and intracellular patch-clamp solution compatible with RT-PCR. To ensure a selective and reliable transcript detection, this technique also requires appropriate controls from cytoplasm harvesting to amplification steps. Although precautions discussed here must be strictly followed, virtually any electrophysiological laboratory can use the multiplex single cell RT-PCR technique.

  View details for DOI 10.3791/57627

  View details for Web of Science ID 000444752100075

  View details for PubMedID 29985318

  View details for PubMedCentralID PMC6101963

• Depdc5 knockdown causes mTOR-dependent motor hyperactivity in zebrafish ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY de Calbiac, H., Dabacan, A., Marsan, E., Tostivint, H., Devienne, G., Ishida, S., Leguern, E., Baulac, S., Muresan, R. C., Kabashi, E., Ciura, S. 2018; 5 (5): 510–23

  Abstract

  DEPDC5 was identified as a major genetic cause of focal epilepsy with deleterious mutations found in a wide range of inherited forms of focal epilepsy, associated with malformation of cortical development in certain cases. Identification of frameshift, truncation, and deletion mutations implicates haploinsufficiency of DEPDC5 in the etiology of focal epilepsy. DEPDC5 is a component of the GATOR1 complex, acting as a negative regulator of mTOR signaling.Zebrafish represents a vertebrate model suitable for genetic analysis and drug screening in epilepsy-related disorders. In this study, we defined the expression of depdc5 during development and established an epilepsy model with reduced Depdc5 expression.Here we report a zebrafish model of Depdc5 loss-of-function that displays a measurable behavioral phenotype, including hyperkinesia, circular swimming, and increased neuronal activity. These phenotypic features persisted throughout embryonic development and were significantly reduced upon treatment with the mTORC1 inhibitor, rapamycin, as well as overexpression of human WT DEPDC5 transcript. No phenotypic rescue was obtained upon expression of epilepsy-associated DEPDC5 mutations (p.Arg487* and p.Arg485Gln), indicating that these mutations cause a loss of function of the protein.This study demonstrates that Depdc5 knockdown leads to early-onset phenotypic features related to motor and neuronal hyperactivity. Restoration of phenotypic features by WT but not epilepsy-associated Depdc5 mutants, as well as by mTORC1 inhibition confirm the role of Depdc5 in the mTORC1-dependent molecular cascades, defining this pathway as a potential therapeutic target for DEPDC5-inherited forms of focal epilepsy.

  View details for DOI 10.1002/acn3.542

  View details for Web of Science ID 000431968300001

  View details for PubMedID 29761115

  View details for PubMedCentralID PMC5945968