Abstract TP333: Motor Recovery After Transient Middle Cerebral Artery Occlusion May be Impacted by the Disruption of Nucleus Basalis-Cortical Cholinergic Pathways

Abstract

Stroke survivors often have chronic motor deficits that significantly impact their quality of life. The most common vessel affected by ischemic events is the middle cerebral artery. These strokes commonly affect the basal ganglia and internal capsule in humans and in rodent models of stroke. Our lab studies the neurotransmitter acetylcholine for its potential to drive cortical plasticity that may support recovery after cortical spinal tract damage. Cholinergic cells in the nucleus basalis (NB), a major cholinergic nucleus with axonal projections throughout the cortex, can drive the beneficial motor map reorganization induced by vagus nerve stimulation after stroke in rats (Kilgard et al., 2016). Our lab has previously shown that selective injury to NB cholinergic cells reduces motor recovery (Becker et al., Soc. for Neuroscience abstract. 800.09, 2014.). In the current experiments, we mapped NB projection pathways in transgenic mice expressing fluorescent proteins in cholinergic neurons. We crossed mice expressing Cre driven by the choline acetyltransferase (ChAT) promoter with mice expressing channelrhodopsin and EYFP with a floxed stop cassette driven by the CAG promoter, both obtained from Jackson Laboratories. Fixed brains were imaged with high-throughput fluorescence microscopy using either whole slide imaging of freezing microtome sections (Nanozoomer, Hamamatsu) or serial two-photon tomography of whole brains (TissueCyte 1000, TissueVision). Cholinergic cell bodies in the NB and their proximal processes were visually tracked from the basal forebrain to the cortex. We found that some NB cholinergic projections to motor cortex were immediately adjacent to the globus pallidus interna, which is typically injured by transient middle cerebral artery occlusion. If the axons of NB cholinergic cells that are projecting to the cortex are damaged by stroke, this pathway may impact the ability for stroke patients to recover motor functions by disrupting central motor learning pathways. Understanding neuromodulatory circuits involved in cortical plasticity and motor learning after stroke is essential for developing new therapeutic methods.