GABAergic Synapses in the Cerebellum
This group studies various aspects of gabaergic synaptic transmission in cerebellar slices.
The cerebellar interneuron network
Interneurons (stellate and basket cells) of the molecular layer are interconnected by chemical (gabaergic) synapses, as well as by electrical synapses. This network is functionally isolated in slice preparations because excitatory inputs are inactive. In the past we have been studying this network in detail, notably focusing on interactions of chemical synapses with the excitability of interneurons (Chavas and Marty, 2003). Current work focuses on the role of electrical synapses as well as the effects exerted by interneurons on Purkinje cells (Oldfield et al., 2010).
Autoreceptors and presynaptic receptors
We have shown that, following the release of GABA from interneuron terminals, GABA binds to axonal receptors located on the releasing cell and elicits GABAA (bicuculline-sensitive) currents (Pouzat and Marty, 1999). These autoreceptor currents enhance the excitability of the axon and give rise to burst discharges (Mejia-Gervacio and Marty, 2006). They are also responsible for a tonic increase of the release probability under resting conditions (Trigo et al., 2007). Presynaptic GABAA receptors are present not only on gabaergic axons of interneurons, but also on parallel fibers (Stell et al., 2007). On parallel fibers, they are not active under resting conditions, and their activation by spillover GABA facilitates glutamatergic release (Stell 2011).
Using paired recordings we have shown that somatic depolarization results in an increase of asynchronous presynaptic GABA release (Glitsch and Marty, 1999). This effect is presumably due to passive transmission of the somatic potential to the presynaptic terminal through the axon cable (Mejia-Gervacio et al., 2007). Passive electrical coupling through the axon cable is also responsible for a novel synaptic signal : presynaptic miniature currents, or preminis (Trigo et al., 2010). One vesicular release event actually gives rise to two simultaneous signals : a (postsynaptic) miniature current, and a presynaptic signal generated by axonal autoreceptors and transmitted to the soma by passive cable properties. Preminis are seen only during development of the molecular layer and are presumably involved in synapse formation and stabilisation.
Collaborative project funded by European Research Council : Single synaptic sites
In collaboration with the teams led by David Ogden and by Isabel Llano/Thibault Collin, we have launched a new project aiming at the study of single synaptic sites at MLI-MLI synapses. Procedures are developed to elicit GABA release at one synaptic site only, and to collect the corresponding presynaptic and postsynaptic signals (see Figure). In this way an array of basic questions concerning synaptic physiology are examined, including the degree of receptor occupancy following one exocytotic event, the existence and number of vesicle docking sites, and the size of the readily releasable pool of vesicles.
Having established a paired recording between synaptically connected neurons, potential synaptic contacts are illuminated with a small laser spot. Laser illumination elicits calcium release from DM-nitrophen, which is included in the presynaptic recording pipette, and elicits quantal repsonses in the postsynaptic cell.
- Alain MARTY, CNRS researcher, DR-CNRS, GABAergic Synapses in the Cerebellum
- alain.marty@-Code a retirer pour éviter le SPAM-parisdescartes.fr, +33 1 42 86 38 36, room E358
- Brandon STELL, CNRS researcher, CR-CNRS, GABAergic Synapses in the Cerebellum
- brandon.stell@-Code a retirer pour éviter le SPAM-parisdescartes.fr
- Kris Elliot BLANCHARD TAPIA, PhD student, GABAergic Synapses in the Cerebellum
- keblanch@-Code a retirer pour éviter le SPAM-gmail.com, +33 1 42 86 38 31, room H347
- Gerardo MALAGON, PhD student, GABAergic Synapses in the Cerebellum
- gerardo.malagon@-Code a retirer pour éviter le SPAM-parisdescartes.fr, +33 1 42 86 38 29, room H356
- Jorge RAMIREZ, PhD student, GABAergic Synapses in the Cerebellum
- jerburi@-Code a retirer pour éviter le SPAM-gmail.com, +33 1 42 86 38 29, room H356
- Federico TRIGO, Assistant professor, Paris Descartes, GABAergic Synapses in the Cerebellum
- federico.trigo@-Code a retirer pour éviter le SPAM-parisdescartes.fr, +33 1 42 86 38 28, room H346
- Axonal GABAA receptors depolarize presynaptic terminals and facilitate transmitter release in cerebellar Purkinje cells.
Zorrilla de San Martin J, Trigo FF, Kawaguchi SY : J Physiol, 2017
- Calcium imaging reveals coordinated simple spike pauses in populations of Cerebellar Purkinje cells
Ramirez JE, Stell BM : BioRxiv, 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
- Impact of single-site axonal GABAergic synaptic events on cerebellar interneuron activity.
Zorrilla de San Martín J, Jalil A, Trigo FF : J Gen Physiol, 2015
- 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
- Synthesis and biological evaluation of bis-CNB-GABA, a photoactivatable neurotransmitter with low receptor interference and chemical two-photon uncaging properties.
Shi DD, Trigo FF, Semmelhack MF, Wang SS : J Am Chem Soc, 2014
- Activation of presynaptic GABA(B(1a,2)) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses.
Wedemeyer C, Zorrilla de San Martín J, Ballestero J, Gómez-Casati ME, Torbidoni AV, Fuchs PA, Bettler B, Elgoyhen AB, Katz E : J Neurosci, 2013
- Functional patterned multiphoton excitation deep inside scattering tissue
Papagiakoumou E, Bègue A, Leshem B, Schwartz O, Stell BM, Bradley J, Oron D, Emiliani V : Nature Photonics, 2013
- Estimating functional connectivity in an electrically coupled interneuron network.
Alcami P, Marty A : Proc Natl Acad Sci U S A, 2013
- Readily releasable pool of synaptic vesicles measured at single synaptic contacts.
Trigo FF, Sakaba T, Ogden D, Marty A : Proc Natl Acad Sci U S A, 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