Adeno-associated viral (AAV) vectors are effective gene therapy delivery candidates, and the AAV-PhP.eB capsid is effective at transducing the CNS in mice when delivered intravenously (IV). Introduction of promoter sequences to the AAV-PhP.eB genome can restrict gene expression to specific cell types. More research is needed to identify cell-specific promoter sequences that restrict gene expression to specific CNS targets. Thus, the Ple394 and Ple394-HBB sequences were examined to see if they can restrict gene expression to cortical neurons. The HB9 sequence was examined to see it could restrict gene expression to spinal motor neurons. The Ple394 promoter resulted in strong cortical neuron gene expression and comparatively less gene expression in off-target brain and spinal cord regions. The Ple394 vector did not result in significantly different gene expression in the liver compared to mice that received saline. The Ple394-HBB promoter failed to cause cortical neuron-specific gene expression. The HB9 promoter resulted in spinal motor neuron-specific gene expression with relatively little expression in the brain. The HB9 vector didn’t result in significantly different gene expression in the liver compared to mice that received saline. In conclusion, introduction of the Ple394 and HB9 promoter sequences into the AAV-PhP.eB genome were able to restrict gene expression to cortical neurons and spinal motor neurons, respectively. Identification of promoters that can drive selective gene expression in the cerebral cortex or spinal motor neurons will allow for the IV delivery of AAV gene therapies to treat diseases such as Alzheimer’s disease or amyotrophic lateral sclerosis, respectively.