Fos‐CreER‐based genetic mapping of forebrain regions activated by acupuncture. Issue 6 (12th November 2019)

• Record Type: Journal Article
• Authors: Guo, Zhiling; Lin, Xiaoxiao; Samaniego, Tracy; Isreb, Alexander; Cao, Stacey; Malik, Shaista; Holmes, Todd C.; Xu, Xiangmin
• Is Part Of: Journal of comparative neurology. Volume 528:Issue 6(2020)
• Page Start: 953
• Page End: 971
• Publication Date: 2019-11-12
• Subjects: acupuncture -- brain -- Fos -- RRID: MGI:5488917 -- sensory nerves -- mouse genetics; Comparative neurobiology -- Periodicals; Neurology -- Periodicals; 616
• DOI: 10.1002/cne.24789
• Languages: English
• ISSNs: 0021-9967

Abstract

Abstract: Acupuncture increasingly is accepted as a potential therapy for many diseases in the Western world. However, the mechanism of acupuncture is not well understood mechanistically. We have established that manual acupuncture (MA) at the Neiguan (P6) acupoint inhibits excitatory cardiovascular reflex responses through modulation of the autonomic nervous system in the brainstem. It is unclear whether P6 MA activates neurons in the brain regions beyond the brainstem. Thus, we mapped P6 specific neural activation by MA in the forebrain using the Fos‐CreER; Ai9 mice model, which allows for enhanced sensitivity and efficiency compared to conventional immunohistochemical staining. Compared to sham‐MA control without manual stimulation, we find that MA at P6 markedly increases c‐Fos positive neurons in a number of the forebrain regions ( n = 5 in each group). These activated regions include accumbens nucleus, caudate putamen, claustrum, bed nucleus of the stria terminalis, amygdaloid nucleus, ventral posterior division of the thalamic nucleus, paraventricular hypothalamic nucleus, arcuate hypothalamic nucleus, primary and secondary somatosensory cortex, ectorhinal cortex, and dorsolateral entorhinal cortex. As MA at P6 activates neurons in relatively broad brain networks beyond the brainstem, our data suggest that acupuncture at this acupoint has the potential to influence physiological functions associated with autonomic and non‐autonomic nervous systems through its effects on multiple brain regions. Abstract : We have established that manual acupuncture (MA) at the Neiguan (P6) acupoint modulates cardiovascular responses through influence on the autonomic nervous system in the brainstem. It is unclear about neuronal activation by P6 MA in the brain regions beyond the brainstem. In the present study, we find that in the Fos‐CreER; Ai9 mice model, MA at P6 markedly increases c‐Fos positive neurons in a number of forebrain regions, including somatosensory cortex (S), ectorhinal cortex (Ect), and dorsolateral entorhinal cortex (DLEnt), claustrum (CI), accumbens nucleus (Acb), caudate putamen (CPu), basolateral (BL) and central (Ce) divisions of amygdaloid nucleus, bed nucleus of the stria terminalis (STLD), ventral posterior division of the thalamic nucleus (VP), paraventricular hypothalamic nucleus (PVN), and arcuate hypothalamic nucleus (Arc). These activated regions likely form potential networks (indicated by dash lines) to influence physiological functions. A microscopic image shows an example of c‐Fos expression (indicated by an arrow) in the Arc of a representative mouse following P6 acupuncture treatment.