Abstract: Olfactory bulb (OB) granule cells (GCs) represent a useful model to study synaptogenesis in adult brain, because they constantly arise from neuronal progenitors and integrate into pre-existing neuronal circuits. Once mature, newborn GCs provide most GABAergic inputs onto mitral/tufted cells, forming reciprocal, dendrodendritic synapses containing the GABAA receptor alpha1/alpha3 subunit in the external plexiform layer (EPL). In turn, GCs receive inhibitory synaptic inputs from local GABAergic interneurons, mediated by alpha2-GABAA receptors, and glutamatergic synaptic inputs from mitral/tufted cells and centrifugal afferents. The aim of this study was to investigate the spatial and temporal pattern of newborn GC synaptogenesis in the adult mouse OB. Using immunoelectron microscopy, we first established that GCs receive axo-dendritic GABAergic synapses stained with gephyrin. Next, we characterized morphologically and electrophysiologically the development of GABAergic and glutamatergic synapses in eGFP-positive newborn GCs labeled by transduction with a lentiviral vector. Already when reaching the GC layer (GCL), at 3 days post-virus injection (dpi), new GCs exhibited tiny voltage-dependent sodium currents and expressed functional GABAergic and glutamatergic synapses located on the soma and dendrites, and recognized immunohistochemically by apposition of specific pre- and postsynaptic markers. Between 3 and 7 dpi, the number of functional synaptic contacts in the GCL increased dramatically and at 7 dpi, PSD95 clusters were predominant over gephyrin clusters. Thus, maturation of glutamatergic synapses was lagging behind GABAergic inputs. eGFP-positive dendrites reached the EPL at 4 dpi, where they formed presumptive reciprocal synapses, which were confirmed ultrastructurally at 7dpi. These synapses were initially formed on the shaft of developing GCs, suggesting that they might induce spine formation. These findings unravel a rapid synaptic integration of newborn GCs in adult mouse OB, with GABAergic and glutamatergic influences being present prior to formation of output synapses onto mitral/tufted cells.
Rapid synaptic integration of newborn granule cells in the adult mouse olfactory bulb
PANZANELLI, Patrizia;PALLOTTO, MARTA;SASSOE' POGNETTO, Marco;
2009-01-01
Abstract
Abstract: Olfactory bulb (OB) granule cells (GCs) represent a useful model to study synaptogenesis in adult brain, because they constantly arise from neuronal progenitors and integrate into pre-existing neuronal circuits. Once mature, newborn GCs provide most GABAergic inputs onto mitral/tufted cells, forming reciprocal, dendrodendritic synapses containing the GABAA receptor alpha1/alpha3 subunit in the external plexiform layer (EPL). In turn, GCs receive inhibitory synaptic inputs from local GABAergic interneurons, mediated by alpha2-GABAA receptors, and glutamatergic synaptic inputs from mitral/tufted cells and centrifugal afferents. The aim of this study was to investigate the spatial and temporal pattern of newborn GC synaptogenesis in the adult mouse OB. Using immunoelectron microscopy, we first established that GCs receive axo-dendritic GABAergic synapses stained with gephyrin. Next, we characterized morphologically and electrophysiologically the development of GABAergic and glutamatergic synapses in eGFP-positive newborn GCs labeled by transduction with a lentiviral vector. Already when reaching the GC layer (GCL), at 3 days post-virus injection (dpi), new GCs exhibited tiny voltage-dependent sodium currents and expressed functional GABAergic and glutamatergic synapses located on the soma and dendrites, and recognized immunohistochemically by apposition of specific pre- and postsynaptic markers. Between 3 and 7 dpi, the number of functional synaptic contacts in the GCL increased dramatically and at 7 dpi, PSD95 clusters were predominant over gephyrin clusters. Thus, maturation of glutamatergic synapses was lagging behind GABAergic inputs. eGFP-positive dendrites reached the EPL at 4 dpi, where they formed presumptive reciprocal synapses, which were confirmed ultrastructurally at 7dpi. These synapses were initially formed on the shaft of developing GCs, suggesting that they might induce spine formation. These findings unravel a rapid synaptic integration of newborn GCs in adult mouse OB, with GABAergic and glutamatergic influences being present prior to formation of output synapses onto mitral/tufted cells.
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