TY - JOUR
T1 - Recurrent network activity drives striatal synaptogenesis
AU - Kozorovitskiy, Yevgenia
AU - Saunders, Arpiar
AU - Johnson, Caroline A.
AU - Lowell, Bradford B.
AU - Sabatini, Bernardo L.
N1 - Funding Information:
Acknowledgements We thank Sabatini laboratory members for comments on the manuscript; B. Roth, K. Deisseroth and M. During for AAV backbones encoding hM4D, ChR2 and Cre, respectively; and C. Gerfen for the Rbp4-Cre mouse line. Confocal imaging was done through the Harvard NeuroDiscovery and Olympus Imaging Centers. This work was supported by grants from NINDS (NS046579, B.L.S); the W.F. Milton Fund Award and the Leonard and Isabelle Goldenson Research Fellowship (Y.K.); and NIH (F31 NS074842) and Shapiro predoctoral fellowship (A.S.).
PY - 2012
Y1 - 2012
N2 - Neural activity during development critically shapes postnatal wiring of the mammalian brain. This is best illustrated by the sensory systems, in which the patterned feed-forward excitation provided by sensory organs and experience drives the formation of mature topographic circuits capable of extracting specific features of sensory stimuli. In contrast, little is known about the role of early activity in the development of the basal ganglia, a phylogenetically ancient group of nuclei fundamentally important for complex motor action and reward-based learning. These nuclei lack direct sensory input and are only loosely topographically organized, forming interlocking feed-forward and feed-back inhibitory circuits without laminar structure. Here we use transgenic mice and viral gene transfer methods to modulate neurotransmitter release and neuronal activity in vivo in the developing striatum. We find that the balance of activity between the two inhibitory and antagonist pathways in the striatum regulates excitatory innervation of the basal ganglia during development. These effects indicate that the propagation of activity through a multi-stage network regulates the wiring of the basal ganglia, revealing an important role of positive feedback in driving network maturation.
AB - Neural activity during development critically shapes postnatal wiring of the mammalian brain. This is best illustrated by the sensory systems, in which the patterned feed-forward excitation provided by sensory organs and experience drives the formation of mature topographic circuits capable of extracting specific features of sensory stimuli. In contrast, little is known about the role of early activity in the development of the basal ganglia, a phylogenetically ancient group of nuclei fundamentally important for complex motor action and reward-based learning. These nuclei lack direct sensory input and are only loosely topographically organized, forming interlocking feed-forward and feed-back inhibitory circuits without laminar structure. Here we use transgenic mice and viral gene transfer methods to modulate neurotransmitter release and neuronal activity in vivo in the developing striatum. We find that the balance of activity between the two inhibitory and antagonist pathways in the striatum regulates excitatory innervation of the basal ganglia during development. These effects indicate that the propagation of activity through a multi-stage network regulates the wiring of the basal ganglia, revealing an important role of positive feedback in driving network maturation.
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U2 - 10.1038/nature11052
DO - 10.1038/nature11052
M3 - Article
C2 - 22660328
AN - SCOPUS:84863744270
SN - 0028-0836
VL - 485
SP - 646
EP - 650
JO - Nature
JF - Nature
IS - 7400
ER -