| 2019 | Somatostatin 2 Receptors in the Spinal Cord Tonically Restrain Thermogenic, Cardiac and Other Sympathetic Outflows. | Front Neurosci | The anatomical and functional characterization of somatostatin (SST) and somatostatin receptors (SSTRs) within the spinal cord have been focused in the dorsal horn, specifically in relation to sensory afferent processing. However, SST is also present within the intermediolateral cell column (IML), which contains sympathetic preganglionic neurons (SPN). We investigated the distribution of SSTR2 within the thoracic spinal cord and show that SSTR2A and SSTR2B are expressed in the dorsal horn and on SPN and non-SPN in or near the IML. The effects of activating spinal SSTR and SSTR2 were sympathoinhibition, hypotension, bradycardia, as well as decreases in interscapular brown adipose tissue temperature and expired CO, in keeping with the well-described inhibitory effects of activating SSTR receptors. These data indicate that spinal SST can decrease sympathetic, cardiovascular and thermogenic activities. Unexpectedly blockade of SSTR2 revealed that SST tonically mantains sympathetic, cardiovascular and thermogenic functions, as activity in all measured parameters increased. In addition, high doses of two antagonists evoked biphasic responses in sympathetic and cardiovascular outflows where the initial excitatory effects were followed by profound but transient falls in sympathetic nerve activity, heart rate and blood pressure. These latter effects, together with our findings that SSTR2A are expressed on GABAergic, presumed interneurons, are consistent with the idea that SST2R tonically influence a diffuse spinal GABAergic network that regulates the sympathetic cardiovascular outflow. As described here and elsewhere the source of tonically released spinal SST may be of intra- and/or supra-spinal origin. |
| 2015 | Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function. | Brain Res | Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate. |
| 2006 | Immunoreactivity for cocaine- and amphetamine-regulated transcript in rat sympathetic preganglionic neurons projecting to sympathetic ganglia and the adrenal medulla. | J Comp Neurol | Many sympathetic preganglionic neurons (SPN) in the intermediolateral cell column (IML) contain cocaine- and amphetamine-regulated transcript (CART), but the function of these CART-immunoreactive (IR) neurons is unknown. To test the possibility that CART might mark SPN involved in cardiovascular regulation, we first established whether all CART neurons in the spinal cord were SPN by double-immunofluorescent labelling for CART and choline acetyltransferase (ChAT). All autonomic subnuclei contained SPN immunoreactive for ChAT plus CART. Occasional ChAT-negative, CART-positive neurons occurred adjacent to the IML, indicating the existence of CART-IR interneurons. We then retrogradely labelled SPN with cholera toxin subunit B (CTB) from a variety of targets and used double immunofluorescence to detect CTB and CART. Among SPN in the IML, 43% projecting to the coeliac ganglion, 34% projecting to the major pelvic ganglion, and about 15% projecting to the superior cervical ganglion or adrenal medulla contained CART. CART also occurred in most SPN projecting to the major pelvic ganglion from either the central autonomic area (63%) or the intercalated nucleus (58%). Finally, we used drug-induced hypotension in conscious rats to evoke Fos immunoreactivity in barosensitive SPN and immunostained to reveal Fos and CART. CART immunoreactivity was present in 41% of the Fos-IR barosensitive neurons, which were concentrated in the IML of segments T5-T13. CART-positive, Fos-negative neurons also occurred in the same segments. These results indicate that CART occurs in barosensitive SPN, nonbarosensitive SPN, and interneurons. Thus, CART is not an exclusive marker for cardiovascular SPN but is likely to influence many autonomic activities. |
| 2002 | Neurochemistry of nerve fibers apposing sympathetic preganglionic neurons activated by sustained hypotension. | J Comp Neurol | Sympathetic preganglionic neurons (SPN) in rat spinal cord were activated by the reflex stimulation of bulbospinal sympathetic neuronal pathways after a nitroprusside-induced hypotension. Hypotension-sensitive SPN, identified by immunoreactivity (IR) to the product of the immediate early gene c-fos and to choline acetyltransferase, were localized in the intermediolateral cell column of thoracic and upper lumbar cord, particularly middle to lower thoracic cord. Putative neurotransmitters, or their markers, in varicose fiber networks around SPN were identified. Nearly all hypotension-sensitive (Fos-IR) SPN were apposed by varicose fibers immunoreactive for tyrosine hydroxylase, serotonin, substance P, or enkephalin. Neuropeptide Y (NPY)- or phenylethanolamine-N-methyl transferase (PNMT)-IR varicose fibers apposed Fos-IR SPN in the upper and middle thoracic spinal cord, but in lower thoracic segments some Fos-IR SPN lacked these appositions. In thoracic segment 12, 51% +/- 5% of Fos-IR SPN (n = 9 rats) lacked PNMT contacts and 25% +/- 3% of Fos-IR SPN (n = 8 rats) lacked NPY contacts. In contrast to other chemically defined afferents, galanin-IR varicose fibers apposed fewer than half of the Fos-IR SPN in the middle to lower thoracic cord. Neurotransmitters/neuromodulators that might influence the activity of SPN acting in the baroreflex-mediated control of blood pressure have been identified. Uniformity in the neurochemistry of some fibers making connections with Fos-IR SPN, regardless of their segmental origin, suggests that common sets of neurons provide convergent inputs to all hypotension-sensitive SPN. Other fibers show topographic differences in their contacts with Fos-IR SPN, suggesting that subgroups of hypotension-sensitive SPN are targeted by particular neuron groups. |
| 2001 | Neurokinin-1 receptor immunoreactivity in hypotension sensitive sympathetic preganglionic neurons. | Brain Res | Substance P activation of neurokinin-1 (NK1) receptors on spinal sympathetic preganglionic neurons (SPN) influences blood pressure. We identified SPN likely to subserve the baroreceptor reflex and established if these neurons showed NK1 receptor-immunoreactivity. Nitroprusside (NP) infusion or inferior vena cava (IVC) constriction activated similar numbers of SPN. Of these, about 40% were NK1 receptor-immunoreactive after NP infusion, but only about 20% were NK1 receptor-immunoreactive after IVC constriction. The distribution of Fos/NK1 receptor SPN suggested that substance P may preferentially target sympathoadrenal SPN. |
| 2001 | Changes in synaptic inputs to sympathetic preganglionic neurons after spinal cord injury. | J Comp Neurol | Spinal cord injury (SCI) leads to plastic changes in organization that impact significantly on central nervous control of arterial pressure. SCI causes hypotension and autonomic dysreflexia, an episodic hypertension induced by spinal reflexes. Sympathetic preganglionic neurons (SPNs) respond to SCI by retracting and then regrowing their dendrites within 2 weeks of injury. We examined changes in synaptic input to SPNs during this time by comparing the density and amino acid content of synaptic input to choline acetyltransferase (ChAT)-immunoreactive SPNs in the eighth thoracic spinal cord segment (T8) in unoperated rats and in rats at 3 days or at 14 days after spinal cord transection at T4. Postembedding immunogold labeling demonstrated immunoreactivity for glutamate or gamma-aminobutyric acid (GABA) within presynaptic profiles. We counted the number of presynaptic inputs to measured lengths of SPN somatic and dendritic membrane and identified the amino acid in each input. We also assessed gross changes in the morphology of SPNs using retrograde labeling with cholera toxin B and light microscopy to determine the structural changes that were present at the time of evaluation of synaptic density and amino acid content. At 3 days after SCI, we found that retrogradely labeled SPNs had shrunken somata and greatly shortened dendrites. Synaptic density (inputs per 10-microm membrane) decreased on ChAT-immunoreactive somata by 34% but increased on dendrites by 66%. Almost half of the inputs to SPNs lacked amino acids. By 14 days, the density of synaptic inputs to dendrites and somata decreased by 50% and 70%, respectively, concurrent with dendrite regrowth. The proportion of glutamatergic inputs to SPNs in spinal cord-transected rats ( approximately 40%) was less than that in unoperated rats, whereas the GABAergic proportion (60-68%) increased. In summary, SPNs participate in vasomotor control after SCI despite profound denervation. An altered balance of excitatory and inhibitory inputs may explain injury-induced hypotension. |