Absence of Large-Scale Dendritic Plasticity of Layer 5 Pyramidal Neurons in Peri-Infarct Cortex

Abstract

When stroke or traumatic brain injury lead to cortical damage, how do surviving neurons rewire the brain to restore lost functionalities? Several Golgi studies have argued for de novo growth and branching of dendrites of pyramidal neurons in the spared hemisphere, but the results could not always be replicated. Functional brain imaging studies in humans and rodents suggest that significant neuronal plasticity occurs in areas surrounding the cortical lesion, but whether dendritic rearrangements occur there has been less well studied, especially after stroke. We used in vivo two-photon microscopy in adult mice expressing green fluorescent protein to monitor longitudinally the length and branch complexity of entire apical dendritic arbors from layer 5 pyramidal neurons distributed over a large peri-infarct cortex region after middle cerebral artery occlusion. We find no evidence of growth of dendrites or addition of new branches to their arbors over a period of 3 months after stroke. Instead, we observed a two-step pruning process: an initial decrease in dendritic length, followed by a loss of dendritic branches. Importantly, the shortening of branch tips reflected a general shrinkage in the dendritic apical tree, suggesting that mechanical forces attributable to the involution of the infarct contributed to the changes in dendritic length. These results help resolve a long-standing debate regarding the role of large-scale dendritic plasticity of pyramidal neurons in functional recovery after cortical injury.

Optical imaging of disrupted functional connectivity following ischemic stroke in mice

“…10, S5 ) with the infarct tissue having the highest positive correlation with surrounding brain regions. Apparent increased contralesional intrahemispheric connectivity would be inconsistent with prior animal studies showing no change in dendritic morphology in the intact hemisphere following unilateral stroke [13, 14]. And, while significant increased anatomical connectivity has been observed in the intact hemisphere using manganese-enhanced MRI [62–64], unlike the present acute study, those studies were performed up to 10 weeks after tMCAO; time points when remodeling and cortical remapping would have either been initialized or more fully matured.…”

Recent advances in fibre lasers for nonlinear microscopy

“…Applications that require imaging deep in scattering tissues [5], particularly in vivo , showcase the unique advantages of MPM. 2PM has been successfully applied to a variety of deep tissue imaging applications, such as direct visualization of neuronal activity [51] and anatomy [52], developing embryos [53], and tissue morphology and pathology [54,55]. 2PM offers 2 to 3 times greater penetration depth than linear confocal microscopy [56].…”

Selective estrogen receptor modulators (SERMs) enhance neurogenesis and spine density following focal cerebral ischemia

“…It is well known that many neurons in the penumbra lose their dendritic spines in an attempt to survive after cerebral ischemia [45, 46]. Along these lines, dendritic arbor shortening has been reported in the ischemic penumbra in the first weeks following MCAO with further loss of dendritic branches after the first month in cortical pyramidal cells [47]. Another study showed that synaptic density steadily decreased up to one week following global cerebral ischemia [48].…”