Interhemispheric plasticity is mediated by maximal potentiation of callosal inputs

Abstract

Central or peripheral injury causes reorganization of the brain’s connections and functions. A striking change observed after unilateral stroke or amputation is a recruitment of bilateral cortical responses to sensation or movement of the unaffected peripheral area. The mechanisms underlying this phenomenon are described in a mouse model of unilateral whisker deprivation. Stimulation of intact whiskers yields a bilateral blood-oxygen-level−dependent fMRI response in somatosensory barrel cortex. Whole-cell electrophysiology demonstrated that the intact barrel cortex selectively strengthens callosal synapses to layer 5 neurons in the deprived cortex. These synapses have larger AMPA receptor- and NMDA receptor-mediated events. These factors contribute to a maximally potentiated callosal synapse. This potentiation occludes long-term potentiation, which could be rescued, to some extent, with prior long-term depression induction. Excitability and excitation/inhibition balance were altered in a manner consistent with cell-specific callosal changes and support a shift in the overall state of the cortex. This is a demonstration of a cell-specific, synaptic mechanism underlying interhemispheric cortical reorganization.

Mapping the brain-wide network effects by optogenetic activation of the corpus callosum

“…Certainly, the optogenetic callosal fiber activation also elicits the specific unidirectional callosal orthodromic activity as well, similar to earlier reports[43, 44, 46]. In addition, the optogenetic activation of the callosal projection terminals from brain slices leads to better characterization of the excitatory and inhibitory circuit regulation by callosal inputs [56, 58–60, 79]. Our observations further support the non-linear neurovascular coupling events with the optical intrinsic signal measurements and laser-doppler flowmetry upon the optogenetic or electrical CC stimulation [43, 55].…”

Circuit-Specific Plasticity of Callosal Inputs Underlies Cortical Takeover

“…Unilateral whisker denervation increased excitability in CC-targeted L5 neurons in deprived S1BC (Petrus et al, 2019). Our hypothesis was that this change may be restricted to neurons with specific output targets.…”

“…1A, left). Two weeks after ION-X was determined to be the maximal timepoint for plasticity along the intact pathway (Chung et al, 2017;Yu et al, 2012), and robust callosal alterations were also described at this timepoint (Petrus et al, 2019;Yu and Koretsky, 2014). Therefore, acute slices were made two weeks after ION-X and rAAV labeled cells were targeted for whole cell current clamp recordings.…”

“…Other studies indicate that remodeling may be related to phantom limb pain (Flor et al, 2006), however, this cortical remodeling is not consistently observed in phantom limb (Makin et al, 2013(Makin et al, , 2015. A rodent model of unilateral whisker denervation (infraorbital nerve transection: ION-X) mimics some of the changes detected in humans; for example there is potentiation of the pathway into intact primary somatosensory barrel cortex (S1BC) and task-evoked recruitment of deprived S1BC during intact whisker stimulation (Petrus et al, 2019;Yu et al, 2012). The recruitment of deprived S1BC is likely due to potentiation of the corpus callosum (CC) inputs from intact S1BC to deprived S1BC, which was so strong to L5 neurons that long term potentiation (LTP) was occluded (Petrus et al, 2019).…”

“…A rodent model of unilateral whisker denervation (infraorbital nerve transection: ION-X) mimics some of the changes detected in humans; for example there is potentiation of the pathway into intact primary somatosensory barrel cortex (S1BC) and task-evoked recruitment of deprived S1BC during intact whisker stimulation (Petrus et al, 2019;Yu et al, 2012). The recruitment of deprived S1BC is likely due to potentiation of the corpus callosum (CC) inputs from intact S1BC to deprived S1BC, which was so strong to L5 neurons that long term potentiation (LTP) was occluded (Petrus et al, 2019). Interestingly, this plasticity was not found in L2/3 neurons, demonstrating specificity to deep layer neurons.…”