title: Differential Inputs to the Perisomatic and Distal-Dendritic Compartments of VIP-Positive Neurons in Layer 2/3 of the Mouse Barrel Cortex.
abstract: The recurrent network composed of excitatory and inhibitory neurons is fundamental to neocortical function. Inhibitory neurons in the mammalian neocortex are molecularly diverse, and individual cell types play unique functional roles in the neocortical microcircuit. Recently, vasoactive intestinal polypeptide-positive (VIP+) neurons, comprising a subclass of inhibitory neurons, have attracted particular attention because they can disinhibit pyramidal cells through inhibition of other types of inhibitory neurons, such as parvalbumin- (PV+) and somatostatin-positive (SOM+) inhibitory neurons, promoting sensory information processing. Although VIP+ neurons have been reported to receive synaptic inputs from PV+ and SOM+ inhibitory neurons as well as from cortical and thalamic excitatory neurons, the somatodendritic localization of these synaptic inputs has yet to be elucidated at subcellular spatial resolution. In the present study, we visualized the somatodendritic membranes of layer (L) 2/3 VIP+ neurons by injecting a newly developed adeno-associated virus (AAV) vector into the barrel cortex of VIP-Cre knock-in mice, and we determined the extensive ramification of VIP+ neuron dendrites in the vertical orientation. After immunohistochemical labeling of presynaptic boutons and postsynaptic structures, confocal laser scanning microscopy revealed that the synaptic contacts were unevenly distributed throughout the perisomatic (<100 μm from the somata) and distal-dendritic compartments (≥100 μm) of VIP+ neurons. Both corticocortical and thalamocortical excitatory neurons preferentially targeted the distal-dendritic compartment of VIP+ neurons. On the other hand, SOM+ and PV+ inhibitory neurons preferentially targeted the distal-dendritic and perisomatic compartments of VIP+ neurons, respectively. Notably, VIP+ neurons had few reciprocal connections. These observations suggest different inhibitory effects of SOM+ and PV+ neuronal inputs on VIP+ neuron activity; inhibitory inputs from SOM+ neurons likely modulate excitatory inputs locally in dendrites, while PV+ neurons could efficiently interfere with action potential generation through innervation of the perisomatic domain of VIP+ neurons. The present study, which shows a precise configuration of site-specific inputs, provides a structural basis for the integration mechanism of synaptic inputs to VIP+ neurons.
authors.affiliation: Department of Morphological Brain Science, Graduate School of Medicine, Kyoto UniversityKyoto, Japan; Division of Cerebral Circuitry, National Institute for Physiological SciencesOkazaki, Japan.
authors.forename: Jaerin
authors.initials: J
authors.lastname: Sohn
authors.affiliation: Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University Kyoto, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Department of Integrative Physiology, Nagoya University Graduate School of Medicine Nagoya, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kataoka
authors.affiliation: Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: Department of Integrative Physiology, Nagoya University Graduate School of MedicineNagoya, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST)Kawaguchi, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University Kyoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hioki
keywords: GABAergic neuron; barrel cortex; confocal laser scanning microscopy; somatodendritic compartment; vasoactive intestinal polypeptide