A dynamic zone defines interneuron remodeling in the adult neocortex

Abstract

The contribution of structural remodeling to long-term adult brain plasticity is unclear. Here, we investigate features of GABAergic interneuron dendrite dynamics and extract clues regarding its potential role in cortical function and circuit plasticity. We show that remodeling interneurons are contained within a "dynamic zone" corresponding to a superficial strip of layers 2/3, and remodeling dendrites respect the lower border of this zone. Remodeling occurs primarily at the periphery of dendritic fields with addition and retraction of new branch tips. We further show that dendrite remodeling is not intrinsic to a specific interneuron class. These data suggest that interneuron remodeling is not a feature predetermined by genetic lineage, but rather, it is imposed by cortical laminar circuitry. Our findings are consistent with dynamic GABAergic modulation of feedforward and recurrent connections in response to top-down feedback and suggest a structural component to functional plasticity of supragranular neocortical laminae.dendrite ͉ inhibitory ͉ plasticity ͉ two-photon microscopy ͉ visual cortex D espite decades of evidence for functional plasticity of the adult brain, manifested in our ability to learn and the continual adaptation of primary sensory maps (1, 2), the existence and role of structural remodeling (3, 4) in circuit plasticity remains controversial. Structural plasticity of excitatory projection neurons that enables circuit remodeling during development wanes as "critical periods" close and circuits mature, suggesting that in the adult, other mechanisms are likely recruited for functional remodeling.To investigate the extent of structural plasticity in the mammalian brain, we previously used a multiphoton microscope system for chronic in vivo imaging of neuronal morphology in the intact rodent cerebral cortex (5). Using this system, we imaged and reconstructed the dendritic trees of neurons in visual cortex of thy1-GFP-S transgenic mice (6). These mice express GFP in a random subset of neurons sparsely distributed within the superficial cortical layers that are optically accessible through surgically implanted cranial windows. This enables examination of dendritic branch dynamics in individual neurons over several months. Our results confirmed recent in vivo imaging studies showing that excitatory projection neurons show little, if any, change in branch tip length over time (7,8). Surprisingly, we found that GABAergic interneurons in layer (L) 2/3 of visual cortex undergo arbor remodeling occurring over days to weeks (5). Although most work related to circuit plasticity in the adult brain has focused on excitatory connectivity, inhibition is clearly critical for mature circuit function. The superficial neocortical layers contain a remarkably heterogeneous population of nonpyramidal interneurons that differ in their cellular targeting and hence function within the cortical circuit (9-11) and may not be uniform in their propensity for structural change. Stratification of the mammalian neocortex into c...

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