{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:23:06Z","timestamp":1787016186812,"version":"build-2736575974"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Autonomic dysregulation, including sympathetic hyperactivity, is a common feature of hypertension (HT) and other cardiovascular diseases. The CNS plays a role in driving chronic sympathetic activation in disease, but several lines of evidence suggest that neuroplasticity in the periphery may also contribute. The potential contribution of postganglionic sympathetic neurons to sustained sympathetic hyperactivity is not well understood. We recently discovered that noradrenergic sympathetic neurons in the stellate ganglion (SG) have excitatory cholinergic collateral connections to other neurons within the ganglion. We hypothesize that remodelling of these neurons and increased cholinergic collateral transmission contributes to sustained sympathetic hyperactivity in cardiovascular diseases, including HT. To test that hypothesis, we examined the activity of sympathetic neurons in isolated SG under control conditions and after 1\u00a0week of HT induced by peripheral angiotensin II infusion, using whole\u2010cell patch clamp recordings. Despite the absence of central inputs, we observed elevated spontaneous activity and synaptic transmission in sympathetic SG neurons from hypertensive mice that required generation of action potentials. Genetically disrupting cholinergic transmission in noradrenergic neurons decreased basal neuronal activity and prevented angiotensin II\u2010mediated enhancement of activity. Similar changes in activity, driven by increased collateral transmission, were identified in cardiac projecting neurons and neurons projecting to brown adipose tissue. These changes were not driven by altered A\u2010type K\n                      <jats:sup>+<\/jats:sup>\n                      currents. This suggests that HT stimulates increased activity throughout the intraganglionic network of collateral connections, contributing to the sustained sympathetic hyperactivity characteristic in cardiovascular disease.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16174-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Sympathetic neurons in ganglia isolated from angiotensin II\u2010treated hypertensive mice are more active than neurons from control mice despite the absence of central activation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The enhanced activity is the result of a ganglionic network of cholinergic collaterals, rather than altered intrinsic excitability.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Increased neuronal activity was observed in both cardiac neurons and brown adipose tissue\u2010projecting neurons, which are not involved in cardiovascular homeostasis.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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