RT Journal Article
SR Electronic
T1 Vesicular Glutamate Transporter 2 Is Required for Central Respiratory Rhythm Generation But Not for Locomotor Central Pattern Generation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 12294
OP 12307
DO 10.1523/JNEUROSCI.3855-06.2006
VO 26
IS 47
A1 Åsa Wallén-Mackenzie
A1 Henrik Gezelius
A1 Muriel Thoby-Brisson
A1 Anna Nygård
A1 Anders Enjin
A1 Fumino Fujiyama
A1 Gilles Fortin
A1 Klas Kullander
YR 2006
UL http://www.jneurosci.org/content/26/47/12294.abstract
AB Glutamatergic excitatory neurotransmission is dependent on glutamate release from presynaptic vesicles loaded by three members of the solute carrier family, Slc17a6–8, which function as vesicular glutamate transporters (VGLUTs). Here, we show that VGLUT2 (Slc17a6) is required for life ex utero. Vglut2 null mutant mice die immediately after birth because of the absence of respiratory behavior. Investigations at embryonic stages revealed that neural circuits in the location of the pre-Bötzinger (PBC) inspiratory rhythm generator failed to become active. However, neurons with bursting pacemaker properties and anatomical integrity of the PBC area were preserved. Vesicles at asymmetric synapses were fewer and malformed in the Vglut2 null mutant hindbrain, probably causing the complete disruption of AMPA/kainate receptor-mediated synaptic activity in mutant PBC cells. The functional deficit results from an inability of PBC neurons to achieve synchronous activation. In contrast to respiratory rhythm generation, the locomotor central pattern generator of Vglut2 null mutant mice displayed normal rhythmic and coordinated activity, suggesting differences in their operating principles. Hence, the present study identifies VGLUT2-mediated signaling as an obligatory component of the developing respiratory rhythm generator.