Chemogenetic Activation Of Cholinergic Neurons In The Mouse Nucleus Basalis During Stroke Recovery

The cholinergic projection neurons of the nucleus basalis (NB) mediate learning and cortical plasticity. Artificial activation of NB during tone presentation has been shown to increase the representation of paired frequencies in the auditory cortex, and when NB is stimulated during motor behavior it increases task-relevant representations of the cortical motor map. NB activation during successful movements also increases performance after training. We tested the hypothesis that increased activity of NB neurons during rehabilitative motions can improve the extent of stroke recovery. We injected a cre-dependent Gq DREADD (Designer Receptors Activated by Designer Drugs) or control GFP virus bilaterally into the nucleus basalis of transgenic C57/BL6 mice expressing cre in cholinergic neurons. Photothrombotic stroke was then targeted to sensorimotor representations of the forelimb, and performance in the automated reach task used to assess functional deficits and recovery. From weeks 2-6 after stroke, mice received and injection of the DREADD-activating drug clozapine-N-oxide before rehabilitative sessions, and final drug-free performance was assessed at week 7. We see a biologically significant trend toward greater improvement at week 7 after stroke in the average performance of DREADD-injected mice compared to the control group. Methods for improved replication and increasing effect size will be discussed.