Dynamic Reorganization of Neuronal Activity Patterns in Parietal Cortex.

Neuronal representations change as associations are learned between sensory stimuli and behavioral actions. However, it is poorly understood whether representations for learned associations stabilize in cortical association areas or continue to change following learning. We tracked the activity of posterior parietal cortex neurons for a month as mice stably performed a virtual-navigation task. The relationship between cells' activity and task features was mostly stable on single days but underwent major reorganization over weeks. The neurons informative about task features (trial type and maze locations) changed across days. Despite changes in individual cells, the population activity had statistically similar properties each day and stable information for over a week. As mice learned additional associations, new activity patterns emerged in the neurons used for existing representations without greatly affecting the rate of change of these representations. We propose that dynamic neuronal activity patterns could balance plasticity for learning and stability for memory.

Aberrant cortical spine dynamics after concussive injury are reversed by integrated stress response inhibition.

Traumatic brain injury (TBI) is a leading cause of long-term neurological disability in the world and the strongest environmental risk factor for the development of dementia. Even mild TBI (resulting from concussive injuries) is associated with a greater than twofold increase in the risk of dementia onset. Little is known about the cellular mechanisms responsible for the progression of long-lasting cognitive deficits. The integrated stress response (ISR), a phylogenetically conserved pathway involved in the cellular response to stress, is activated after TBI, and inhibition of the ISR-even weeks after injury-can reverse behavioral and cognitive deficits. However, the cellular mechanisms by which ISR inhibition restores cognition are unknown. Here, we used longitudinal two-photon imaging in vivo after concussive injury in mice to study dendritic spine dynamics in the parietal cortex, a brain region involved in working memory. Concussive injury profoundly altered spine dynamics measured up to a month after injury. Strikingly, brief pharmacological treatment with the drug-like small-molecule ISR inhibitor ISRIB entirely reversed structural changes measured in the parietal cortex and the associated working memory deficits. Thus, both neural and cognitive consequences of concussive injury are mediated in part by activation of the ISR and can be corrected by its inhibition. These findings suggest that targeting ISR activation could serve as a promising approach to the clinical treatment of chronic cognitive deficits after TBI.