reconstructing the three-dimensional gabaergic microcircuit of the striatum纹状体的重建三维gaba ergic微电路.pdfVIP

Reconstructing the Three-Dimensional GABAergic Microcircuit of the Striatum 1,2 1 1 Mark D. Humphries *, Ric Wood , Kevin Gurney 1 Adaptive Behaviour Research Group, Department of Psychology, University of Sheffield, Sheffield, United Kingdom, 2 Group for Neural Theory, Department d’Etudes Cognitives, Ecole Normale Superieure, Paris, France Abstract A system’s wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100mm of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas a