Optical probing of the Cerebellar Circuit
Our work in the last decade has aimed at unraveling molecular and cellular aspects of synaptic transmission and intracellular calcium homeostasis in the mammalian cerebellar cortex using electrophysiology and optical techniques approaches. One aspect of this work is the study of the molecular profile and spatial localization of ion channels and transmitter-gated receptors in GABA-releasing neurons in cerebellar slices with focus on molecules governing responses to the excitatory neurotransmitter glutamate.
A second axis of the work is the analysis of calcium signaling in the various compartments of cerebellar neurons, with particular emphasis on activity-dependent calcium signals generated in the axon. Using digital fluorescence imaging and 2 photon laser scanning microscopy, we study the temporal and spatial properties of calcium signals in axonal varicosities of both, interneurons and Purkinje cells. We are interested in how voltage-gated calcium channels, calcium binding proteins and intracellular calcium stores shape calcium signals and subsequent neurotransmitter release. Interactions between metabotropic glutamate receptors (mGluRs) and calcium signaling have also been a recent theme of our studies.
In the past few years, our team has expanded activities from the in vitro slice preparation and we are now also working with an in vivo system. Using 2 photon laser scanning microscopy in anesthetized mice, we first characterized the properties of somatic calcium transients linked with action potentials in molecular layer interneurons loaded with organic calcium indicators. More recently, we are performing in vivo imaging in interneurons from mice expressing various varieties of the genetically-encoded calcium proteins GCaMP3 and GCaMP5.
This recent push to work in vivo gives us the possibility of studying various molecular elements of the cerebellar neurons in the intact animal. For instance, because of our previous work in vitro, showing that mGluRs have a powerful influence on the spiking pattern and intracellular calcium signaling of molecular layer interneurons, we are interested in dissecting the contribution of mGluRs to calcium signals in vivo. We are also interested in probing for the presence of functional presynaptic receptors in the intact animaI and in assessing their role in neuronal integration.
An important goal for the future years will be to link the optical monitoring of neuronal activity with specific sensorimotor tasks in the awake animal. Establishing new procedures to study cerebellar circuits in vivo by the incorporation of new techniques such as local photostimulation or development of novel genetic tools to apply viral mediated expression strategies with appropriate viral vectors is a central goal of our work.
- Thibault COLLIN, Professor, Paris Descartes, Optical probing of the Cerebellar Circuit
- thibault.collin@-Code a retirer pour éviter le SPAM-parisdescartes.fr, +33 1 42 86 38 28, room H346
- Isabel LLANO, Director, DR-CNRS, Optical probing of the Cerebellar Circuit
- isabel.llano@-Code a retirer pour éviter le SPAM-parisdescartes.fr, +33 1 42 86 38 26, room E364
- Michael GRAUPNER, CNRS researcher, CR-CNRS, Optical probing of the Cerebellar Circuit
- michael.graupner@-Code a retirer pour éviter le SPAM-parisdescartes.fr, +33 1 42 86 38 33, room H353
- Merouann KASSA, PhD student, Optical probing of the Cerebellar Circuit
- merouann.kassa@-Code a retirer pour éviter le SPAM-parisdescartes.fr, +33 1 42 86 38 33, room H353
- Concerted Interneuron Activity in the Cerebellar Molecular Layer During Rhythmic Oromotor Behaviors.
Astorga G, Li D, Therreau L, Kassa M, Marty A, Llano I : J Neurosci, 2017
- Updating temporal expectancy of an aversive event engages striatal plasticity under amygdala control.
Dallérac G, Graupner M, Knippenberg J, Martinez RC, Tavares TF, Tallot L, El Massioui N, Verschueren A, Höhn S, Bertolus JB, Reyes A, LeDoux JE, Schafe GE, Diaz-Mataix L, Doyère V : Nat Commun, 2017
- Natural Firing Patterns Imply Low Sensitivity of Synaptic Plasticity to Spike Timing Compared with Firing Rate.
Graupner M, Wallisch P, Ostojic S : J Neurosci, 2016
- Actin- and Myosin-Dependent Vesicle Loading of Presynaptic Docking Sites Prior to Exocytosis.
Miki T, Malagon G, Pulido C, Llano I, Neher E, Marty A : Neuron, 2016
- Counting Vesicular Release Events Reveals Binomial Release Statistics at Single Glutamatergic Synapses.
Malagon G, Miki T, Llano I, Neher E, Marty A : J Neurosci, 2016
- An excitatory GABA loop operating in vivo.
Astorga G, Bao J, Marty A, Augustine GJ, Franconville R, Jalil A, Bradley J, Llano I : Front Cell Neurosci, 2015
- Vesicular release statistics and unitary postsynaptic current at single GABAergic synapses
Pulido C, Trigo FF, Llano I, Marty A : Neuron, 2015
- Memory maintenance in synapses with calcium-based plasticity in the presence of background activity.
Higgins D, Graupner M, Brunel N : PLoS Comput Biol, 2014
- Shift from extracellular signal-regulated kinase to AKT/cAMP response element-binding protein pathway increases survival-motor-neuron expression in spinal-muscular-atrophy-like mice and patient cells.
Branchu J, Biondi O, Chali F, Collin T, Leroy F, Mamchaoui K, Makoukji J, Pariset C, Lopes P, Massaad C, Chanoine C, Charbonnier F : J Neurosci, 2013
- Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine.
Graupner M, Maex R, Gutkin B : PLoS Comput Biol, 2013
- Synaptic input correlations leading to membrane potential decorrelation of spontaneous activity in cortex.
Graupner M, Reyes AD : J Neurosci, 2013
- Calcium-based plasticity model explains sensitivity of synaptic changes to spike pattern, rate, and dendritic location.
Graupner M, Brunel N : Proc Natl Acad Sci U S A, 2012
- Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement.
Tolu S, Eddine R, Marti F, David V, Graupner M, Pons S, Baudonnat M, Husson M, Besson M, Reperant C, Zemdegs J, Pagès C, Hay YA, Lambolez B, Caboche J, Gutkin B, Gardier AM, Changeux JP, Faure P, Maskos U : Mol Psychiatry, 2012
- Current and calcium responses to local activation of axonal NMDA receptors in developing cerebellar molecular layer interneurons.
Rossi B, Ogden D, Llano I, Tan YP, Marty A, Collin T : PLoS One, 2012
- Measuring the firing rate of high-resistance neurons with cell-attached recording.
Alcami P, Franconville R, Llano I, Marty A : J Neurosci, 2012
- Somatic calcium level reports integrated spiking activity of cerebellar interneurons in vitro and in vivo
Franconville R, Revet G, Astorga G, Schwaller B, Llano I : J Neurophysiol, 2011