Abstract 132: Chronic Optogenetic Stimulation of Thalamocortical Projections Promotes Axonal Rewiring and Accelerates Recovery of Function After Somatosensory Cortex Stroke

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Abstract

The majority of stroke survivors must cope with chronic disability of the limbs. Improved limb use is generally accompanied by neuroplasticity in surviving brain areas surrounding the stroke. Modulating this innate plasticity should promote further gains in recovery. One relatively unknown issue in stroke research concerns the role of the thalamus, the brain’s relay center for sensory information en route to the cortex. Unpublished data from our lab has shown that while peri-infarct thalamocortical axons are relatively resilient to the effects of ischemia, they are highly unstable and lose a significant number of synaptic boutons in the first few weeks after stroke. We now expand on this by hypothesizing that optogenetic stimulation of peri-infarct thalamocortical projections will promote axonal rewiring and improve recovery from somatosensory cortex stroke. Axons projecting from the VPL nucleus of the thalamus to primary forelimb somatosensory cortex were co-transfected with a fluorescently tagged adeno-associated virus that expressed channelrhodopsin-2 and mCherry. A chronic cranial window was then implanted to allow for longitudinal in vivo two-photon imaging of superficial thalamic axon terminals before and at various times after photothrombotic stroke. Optogenetic stimulation was driven by a blue LED (475 nm, 6-10mW/mm2) magnetically attached to the cranial window. Optical stimulation (5 ms pulses at 5 Hz every 5 seconds) or control procedures were initiated 3 days after stroke in freely moving mice for 1 hour/day, 5 days/week for 6 weeks after stroke. Behavioural performance on the Tape Removal Test and Ladder Walking Test were assessed once weekly throughout the entire recovery period. Preliminary data show that optogenetic stimulation of thalamocortical projections is associated with an attenuated period of thalamocortical bouton elimination, increased bouton formation and greater stability/persistence of newly formed boutons. Importantly, stimulated mice showed less severe forepaw deficits and faster recovery of sensorimotor function. These studies offer encouraging new insights into the application of optogenetic approaches for improving stroke recovery.

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