Cervical Epidural Electrical Stimulation Increases Respiratory Activity through Somatostatin-Expressing Neurons in the Dorsal Cervical Spinal Cord in Rats

• DOI: 10.1523/jneurosci.1958-21.2022
• Publication Date: 2022-12-07T18:50:11Z
• Authors: Erika L. Galer; Ruyi Huang; Meghna Madhavan; Emily Wang; Yan Zhou; James C. Leiter; Daniel C. Lu
• Keywords: Male; Clinical Sciences; Neurodegenerative; somatostatin; epidural stimulation; Medical and Health Sciences; cervical spinal cord; 03 medical and health sciences; 0302 clinical medicine; Respiratory Rate; 616; Animals; Lung; Research Articles; Neurons; Neurology & Neurosurgery; Biomedical and Clinical Sciences; Psychology and Cognitive Sciences; Neurosciences; Cervical Cord; Electric Stimulation; 3. Good health; Rats; Spinal Cord; Neurological; Female; Somatostatin; Proto-Oncogene Proteins c-fos

We tested the hypothesis that dorsal cervical epidural electrical stimulation (CEES) increases respiratory activity in male and female anesthetized rats. Respiratory frequency minute ventilation were significantly increased when CEES was applied dorsally to C2–C6 region of spinal cord. By injecting pseudorabies virus into diaphragm using c-Fos identify neurons activated during CEES, we found horn cord which co-localized, these expressed somatostatin (SST). Using dual viral infection express inhibitory Designer Receptors Exclusively Activated by Drugs (DREADD), hM4D(Gi), selectively SST-positive cells, inhibited SST-expressing administering Clozapine N-oxide (CNO). During CNO-mediated inhibition neurons, excitation elicited diminished. Thus, cord, likely interneurons, communicated with pattern generating network effect changes ventilation. SIGNIFICANCE STATEMENT A pontomedullary within brainstem generates behaviors are susceptible modulation a variety inputs; sensory motor circuits modulate adapt this output meet demands placed on system. explored increase identified (SST)-expressing (c-Fos-positive) CEES. no longer stimulated neuronal activity, thereby demonstrating SST participate activation affected This work establishes mechanistic foundation repurpose clinically accessible neuromodulatory therapy activate stimulate