|PI of the laboratory: Andrea Volterra |
Tél: 021 692 52 71
Direct supervisor (assistant): Maria Amalia Di Castro
Department: Département de Biologie Cellulaire et de Morphologie (DBCM)
Address: Rue du Bugnon 9, 1005 Lausanne
Synaptic activity is controlled by astrocytes: modalities of activation of presynaptic NMDA receptors
Description of Project:
The strength of synaptic connections in the neuronal circuitry can be modulated in different ways for short or long periods, accounting for various forms of memory storage (Citri & Malenka; 2007). Until recently the plastic control of synaptic strength was thought to be an intrinsic property of the neuronal circuitry. Recent findings, however, show that astrocytes, the most abundant glial cells in the brain, participate to the control of synaptic strength. In particular, astrocytes release modulatory substances, called gliotransmitters, which act directly or indirectly on synapses (Volterra & Meldolesi; 2005). Our lab has contributed to these discoveries by showing that: (a) astrocytes release glutamate, the excitatory transmitter used by 50% of the synapses in the brain, via exocytosis of synaptic-like microvesicles (Bezzi et al.; 2004); (b) astrocytic glutamate activates stimulatory NMDA receptors in nerve terminals, thereby strengthening the connectivity in a memory circuit of the hippocampal formation (the one connecting perforant pathway afferents to granule cells of the dentate gyrus, PP-GC) (Jourdain et al.; 2007).
The project will focus on the clarification of important aspects of astrocyte-neuron communication. Using patch-clamp technique, the student will record synaptic activity in the granule cells in situ. Whole-cell voltage-clamp recordings will be used to monitor the variation of synaptic strength in response to astrocytic activation or direct stimulation of neuronal NMDA receptors. Change in frequency or amplitude of miniature excitatory post-synaptic currents will permit discriminating between pre and post-synaptic modification of synaptic activity. He/She will have the possibility to evaluate the difference between the effect of astrocytic glutamate on synaptic activity and direct activation of neuronal glutamate receptors. This will give an idea of the modalities of glutamate release form astrocytes and its implications in modifying neuronal activity.
The proposed project utilizes advanced electrophysiology methods and is aimed at recruiting a highly motivated student willing to specialize in this approach in a competitive research environment.
- Acute hemibrain horizontal slices (300-400 µm) containing intact perforant-path afferents form 18-24-d-old mice.
- In situ whole-cell patch clamp on hippocampal granule cells and on molecular layer astrocytes.
- Local drug application in the slices, close to neuronal dendrites and astrocytic processes, with picopump.
- Miniature excitatory postsynaptic currents (mEPSCs) recordings and data analysis using Mini-Analysis Program 5.1 (Synaptosoft).
- Evoked excitatory postsynaptic currents (eEPSCs) triggered by an extracellular electrode placed on perforant path afferents and simultaneous recoding on a granule cell neuron. Data analysis with program pClamp 10.1.
- Citri A, Malenka RC (2007). Synaptic Plasticity: Multiple Forms, Functions, and mechanisms. Neuropsychopharmacology. [Epub ahead of print]
- Volterra A, Meldolesi J. Astrocytes, from brain glue to communication elements: the revolution continues (2005). Nature Rev Neurosci.6: 626-40.
- Bezzi P, Gundersen V, Galbete JL, Seifert G, Steinhauser C, Pilati E & Volterra A (2004). Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nature Neurosci. 7: 613-20
- Jourdain P, Bergersen LH, Bhaukaurally K, Bezzi P, Santello M, Domercq M, Matute C, Tonello F, Gundersen V & Volterra A (2007). Glutamate exocytosis form astrocytes controls synaptic strength. Nature Neurosci. 10, 331–33
- Santello M and Volterra A (2009) Synaptic modulation by astrocytes via Ca2+-dependent glutamate release. Neuroscience 158: 253-9.
Link to the group web site