Visual experience sculpts whole-cortex spontaneous infraslow activity patterns through an Arc-dependent mechanism

Abstract

Decades of work in experimental animals has established the importance of visual experience during critical periods for the development of normal sensory-evoked responses in the visual cortex. However, much less is known concerning the impact of early visual experience on the systems-level organization of spontaneous activity. Human resting-state fMRI has revealed that infraslow fluctuations in spontaneous activity are organized into stereotyped spatiotemporal patterns across the entire brain. Furthermore, the organization of spontaneous infraslow activity (ISA) is plastic in that it can be modulated by learning and experience, suggesting heightened sensitivity to change during critical periods. Here we used wide-field optical intrinsic signal imaging in mice to examine whole-cortex spontaneous ISA patterns. Using monocular or binocular visual deprivation, we examined the effects of critical period visual experience on the development of ISA correlation and latency patterns within and across cortical resting-state networks. Visual modification with monocular lid suturing reduced correlation between left and right cortices (homotopic correlation) within the visual network, but had little effect on internetwork correlation. In contrast, visual deprivation with binocular lid suturing resulted in increased visual homotopic correlation and increased anti-correlation between the visual network and several extravisual networks, suggesting cross-modal plasticity. These network-level changes were markedly attenuated in mice with genetic deletion of Arc, a gene known to be critical for activity-dependent synaptic plasticity. Taken together, our results suggest that critical period visual experience induces global changes in spontaneous ISA relationships, both within the visual network and across networks, through an Arc-dependent mechanism.infraslow activity | functional connectivity | visual critical period | activity-regulated cytoskeleton-associated protein

The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer

“…Since Arc has previously been implicated in AMPAR trafficking at synapses and spine elimination (Chowdhury et al, 2006; Mikuni et al, 2013) at weak synapses (Okuno et al, 2012), a potential role for ACBARs may be to eliminate synaptic material. Arc also regulates homeostatic forms of plasticity such as AMPAR scaling (Shepherd et al, 2006) and cross-modal plasticity across different brain regions (Kraft et al, 2017), which could be regulated at the circuit level in a non-cell autonomous manner. We favor the idea that released Arc functions to carry intercellular cargo that alters the state of neighboring cells required for cellular consolidation of information.…”

Experience-dependent development and maintenance of binocular neurons in the mouse visual cortex

“…It is possible that the phenotypes observed in Arc KO mice are due to a lack of ipsilateral pruning/depression and/or potentiation/strengthening of contralateral inputs. Arc may also have a systems-wide role in regulating experience-dependent correlated activity in different brain regions during development 38 , which may occur through non cell-autonomous regulation of synaptic plasticity through intercellular spread of Arc protein capsids 39 . Further studies will be required to determine precisely how Arc regulates cellular changes in V1 during development.…”

Distinct structure of cortical population activity on fast and infraslow timescales

“…Furthermore, both fMRI and other approaches to study mesoscale infraslow cortical dynamics -such as electro-and magneto-encephalography (EEG, ECoG, LFP, MEG, e.g. see Popa et al, 2009;Palva and Palva, 2012;Mitra et al, 2018), and intrinsic and voltage-sensitive fluorescent-protein or dye imaging in experimental animals (White et al, 2011;Chan et al, 2015;Kraft et al, 2017) -cannot characterise individual neurons' relationships to infraslow activity.…”