Vesicular Glutamate Transporter 2 Is Required for Central Respiratory Rhythm Generation But Not for Locomotor Central Pattern Generation

A. Wallen-Mackenzie, H. Gezelius, M. Thoby-Brisson, A. Nygard, A. Enjin, F. Fujiyama, G. Fortin, K. Kullander
Journal of Neuroscience. 2006-11-22; 26(47): 12294-12307
DOI: 10.1523/jneurosci.3855-06.2006

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1. J Neurosci. 2006 Nov 22;26(47):12294-307.

Vesicular glutamate transporter 2 is required for central respiratory rhythm
generation but not for locomotor central pattern generation.

Wallén-Mackenzie A(1), Gezelius H, Thoby-Brisson M, Nygård A, Enjin A, Fujiyama
F, Fortin G, Kullander K.

Author information:
(1)Department of Neuroscience, Unit of Developmental Genetics, Uppsala
University, 751 23 Uppsala, Sweden.

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.

DOI: 10.1523/JNEUROSCI.3855-06.2006
PMCID: PMC6675433
PMID: 17122055 [Indexed for MEDLINE]

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