In Vivo Discharge Properties of Hypothalamic Paraventricular Nucleus Neurons With Axonal Projections to the Rostral Ventrolateral Medulla

Abstract

Chen Q-H, Toney GM. In vivo discharge properties of hypothalamic paraventricular nucleus neurons with axonal projections to the rostral ventrolateral medulla. J Neurophysiol 103: 4 -15, 2010. First published November 4, 2009 doi:10.1152/jn.00094.2009. The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) are key components of a neural network that generates and regulates sympathetic nerve activity (SNA). Although each region has been extensively studied, little is presently known about the in vivo discharge properties of individual PVN neurons that directly innervate the RVLM. Here extracellular recording was performed in anesthetized rats, and antidromic stimulation was used to identify single PVN neurons with axonal projections to the RVLM (n ϭ 94). Neurons were divided into two groups that had either unbranched axons terminating in the RVLM (i.e., PVN-RVLM neurons, n ϭ 65) or collateralized axons targeting both the RVLM and spinal cord [i.e., PVN-RVLM/ intermediolateral cell column (IML) neurons, n ϭ 29]. Many PVN-RVLM (32/65, 49%) and PVN-RVLM/IML (17/29, 59%) neurons were spontaneously active. The average firing frequency was not different across groups. Spike-triggered averaging revealed that spontaneous discharge of most neurons was temporally correlated with renal SNA (PVN-RVLM: 12/21, 57%; PVN-RVLM/IML: 6/9, 67%). Time histograms triggered by the electrocardiogram (ECG) R-wave indicated that discharge of most cells was also cardiac rhythmic (PVN-RVLM: 25/32, 78%; PVN-RVLM/IML: 10/17, 59%). Raising and lowering arterial blood pressure to increase and decrease arterial baroreceptor input caused a corresponding decrease and increase in firing frequency among cells of both groups (PVN-RVLM: 9/13, 69%; PVN-RVLM/IML: 4/4, 100%). These results indicate that PVN-RVLM and PVN-RVLM/IML neurons are both capable of contributing to basal sympathetic activity and its baroreflex modulation.

Role of small conductance calcium-activated potassium channels expressed in PVN in regulating sympathetic nerve activity and arterial blood pressure in rats

“…It is also noteworthy that SK channels are typically able to be activated in neurons through the mechanisms of accumulation of Ca 2ϩ during highfrequency bursts of action potentials (44). Previous in vivo single cell recording studies showed that the majority of presympathetic PVN neurons were silent or firing at low frequency (1-4 Hz) (2,11,12,52). It has been also demonstrated that activation of SK currents is independent on action potential firing frequency (50).…”

“…ACTIVITY of presympathetic hypothalamic paraventricular nucleus (PVN) neurons regulate the sympathetic nervous system (11,12,47,51) response to physiological challenges. These neurons also play a well-described role in activating the sympathetic nervous system in cardiovascular diseases (17,28,36,39,47,48,51,53).…”

Activation of the (pro)renin receptor in the paraventricular nucleus increases sympathetic outflow in anesthetized rats

“…Cultured brain neurons were incubated with 100 nmol/l of human prorenin or vehicle control for differing time periods (1,3,6,12, and 24 h). Cells were collected, and quantitative real-time PCR was performed to measure mRNA levels of genes of interest including inducible nitric oxide synthase (iNOS); FOS-like antigen 1 (fosl1), a neuronal activation marker; and the NAPDH oxidase 2 subunit cybb, using specific primers and probes (Applied Biosystems, Foster City, CA) in the Step One Plus Real Time PCR System (Applied Biosystems).…”

Mechanisms Underlying Hypertension and Obesity

“…Many PVN neurons that project to RVLM also display an intrinsic autorhythmicity, and the discharge frequency correlates closely with sympathetic discharge rate. 3 The relation of PVN neurons to sympathetic control suggests that the spontaneous discharge can be modified through either changes to the intrinsic rate of depolarization or alterations in the balance of excitatory and inhibitory afferent input.Given the role of the PVN in controlling sympathetic activity and its potential contribution to hypertension, research is exploring how PVN activity may be modified by extrinsic inputs. The PVN receives extensive neuronal input from a large number of regions in the brain, including those associated with osmotic control (the subfornical and median preoptic nuclei), appetite and energy metabolism (lateral hypothalamic), limbic nuclei, and other areas that exert effects on blood pressure (eg, lateral parabrachial nucleus, nucleus tractus solitarius, dorsal motor nucleus of the vagus).…”

“…Many PVN neurons that project to RVLM also display an intrinsic autorhythmicity, and the discharge frequency correlates closely with sympathetic discharge rate. 3 The relation of PVN neurons to sympathetic control suggests that the spontaneous discharge can be modified through either changes to the intrinsic rate of depolarization or alterations in the balance of excitatory and inhibitory afferent input.…”