Reduced sensory-evoked structural plasticity in the aging barrel cortex.

Impairments in synaptic connectivity have been linked to cognitive deficits in age-related neurodegenerative disorders and healthy aging. However, the anatomical and structural bases of these impairments have not been identified yet. A hallmark of neural plasticity in young adults is short-term synaptic rearrangement, yet aged animals already display higher synaptic turnover rates at the baseline. Using two-photon excitation (2PE) microscopy, we explored if this elevated turnover alters the aged brain's response to plasticity. Following a sensory-evoked plasticity protocol involving whisker stimulation, aged mice display reduced spine dynamics (gain, loss, and turnover), decreased spine clustering, and lower spine stability when compared to young adult mice. These results suggest a deficiency of the cortical neurons of aged mice to structurally incorporate new sensory experiences, in the form of clustered, long-lasting synapses, into already existing cortical circuits. This research provides the first evidence linking experience-dependent plasticity with in vivo spine dynamics in the aged brain and supports a model of both reduced synaptic plasticity and reduced synaptic tenacity in the aged somatosensory system.

Functional Synaptic Architecture of Callosal Inputs in Mouse Primary Visual Cortex.

Callosal projections are thought to play a critical role in coordinating neural activity between the cerebral hemispheres in placental mammals, but the rules that govern the arrangement of callosal synapses on the dendrites of their target neurons remain poorly understood. Here we describe a high-throughput method to map the functional organization of callosal connectivity by combining in vivo 3D random-access two-photon calcium imaging of the dendritic spines of single V1 neurons with optogenetic stimulation of the presynaptic neural population in the contralateral hemisphere. We find that callosal-recipient spines are more likely to cluster with non-callosal-recipient spines with similar orientation preference. These observations, based on optogenetic stimulation, were confirmed by direct anatomical visualization of callosal synaptic connections using post hoc expansion microscopy. Our results demonstrate, for the first time, that functional synaptic clustering in a short dendritic segment could play a role in integrating distinct neuronal circuits.