Abstract
Astrocytes are key cellular elements in both the tripartite synapse and the neurovascular unit. To fulfill this dual role in synaptic activity and metabolism, they express a panel of receptors and transporters that sense glutamate. Among them, the GLT-1 and GLAST transporters are known to regulate extracellular glutamate concentrations at excitatory synapses and consequently modulate glutamate receptor signaling. These major uptake systems are also involved in energy supply to neurons. However, the functional role of GLAST in concurrent regulation of metabolic and neuronal activity is currently unknown. We took advantage of the attractive structural and functional features of the main olfactory bulb to explore the impact of GLAST on sensory information processing while probing both glutamate uptake and neuronal activity in glomeruli and deeper cellular layers, respectively. Using odor-evoked 2-deoxyglucose imaging and local field potential recordings in GLAST knockout mice, we show in vivo that deletion of GLAST alters both glucose uptake and neuronal oscillations in olfactory bulb networks.
Highlights
Astrocytes are structurally positioned to regulate synaptic transmission and neurovascular coupling: they extend perisynaptic processes that cover thousands of synapses and endfeet that are apposed to the blood vessel wall (Haydon and Carmignoto, 2006)
glutamate aspartate transporter (GLAST) EXPRESSION IN THE OLFACTORY BULB IN ADULT MICE Consistently with previous published data (Utsumi et al, 2001), GLAST immunofluorescence was observed throughout the olfactory bulb (OB), with relatively stronger expression in the glomerular layer (GL) followed by the mitral/tufted cells (M/TCs) layer and external plexiform layer (EPL) (Figure 1A)
NO OVEREXPRESSION OF glutamate transporter 1 (GLT-1) IN THE OLFACTORY BULB OF GLAST−/− ADULT MICE The relative level of expression of GLAST and GLT-1 was measured by immunoblotting of isolated OBs from paired GLAST+/+ and GLAST−/− mice (n = 5 for each; Figure 1B)
Summary
Astrocytes are structurally positioned to regulate synaptic transmission and neurovascular coupling: they extend perisynaptic processes that cover thousands of synapses and endfeet that are apposed to the blood vessel wall (Haydon and Carmignoto, 2006). An increasing number of studies have established their role in the regulation of energy metabolism (Pellerin, 2008), blood flow (Gordon et al, 2008), and synaptic activity (Fellin, 2009) To fulfill this triple role, astrocytes express a repertoire of transporters and receptors to mediate an active molecular crosstalk with neurons. Glutamate transporters (GluTs) GLAST (for GLutamate–ASpartate Transporter, EAAT-1) and GLT-1 (for GLutamate Transporter, EAAT-2) are exclusively expressed by astrocytes and are present at high densities near excitatory synapses (Danbolt, 2001) These transporters prevent excessive accumulation of glutamate and tightly regulate glutamate receptor occupancy and signaling (Huang and Bergles, 2004; Attwell and Gibb, 2005). GLT-1 accounts for the majority of glutamate uptake in the adult forebrain (Rothstein et al, 1994; Ullensvang et al, 1997), but GLAST might be an important contributor in specific pathways
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