Reduced sensory-evoked plasticity in the aging barrel cortex
To learn and form memories, synapses must maintain both the flexibility to adapt in new scenarios and the stability to preserve integrity of the neural circuits associated with those memories. Impairments in synaptic connectivity have been linked to cognitive deficits in both a variety of disorders and in healthy aging. However, the anatomical and structural bases of this impairment 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 baseline. Using two-photon excitation (2PE) microscopy, we explored if this elevated turnover alters the aged brain’s response to a sensory plasticity-inducing scenario by examining dendritic spine behavior in the tuft of layer V pyramidal neurons of primary somatosensory cortex. Following a sensory-evoked plasticity protocol involving whisker stimulation, aged mice displayed a reduction in spine dynamics (gain, loss, and turnover), decreased spine clustering, lower spine stability, and a spine morphological phenotype of synaptic weakening 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. This thesis contributes to an understanding of information processing deficits in the aged brain with a focus on aberrant plasticity of synapses in the distal apical tuft and ways distal tuft plasticity may be modified.