<b>Noradrenergic effects in rat sacral autonomic nucleus using in vitro slice patch-clamp r</b><b>ecordings </b>

Abstract

Noradrenergic modulation has been frequently discussed in the context of neural activities that are related to pelvic organs. The sacral preganglionic nucleus (SPN) is a spinal nucleus containing parasympathetic preganglionic neurons that send fibers to pelvic nerves. In spite of the abundant presence of noradrenergic fibers around the SPN, the effects of noradrenaline (NA) remain obscure. To explore this issue, NA (50 μM) was applied to parasympathetic preganglionic neurons in the SPN during whole-cell patch clamp recording. The SPN was labeled with the retrograde tracer, DiI. These neurons demonstrated two classes of firing patterns (delayed and regular) in terms of initiation of firing. Independent of these firing patterns, NA induced inward (56%) or outward (32%) currents in labeled SPN neurons. Phenylephrine, an α1 receptor agonist, induced an inward current, and clonidine, an α2 receptor agonist, induced an outward current, indicating the existence of both α1 and α2 adrenoreceptors in DiI-labeled SPN neurons. NA also modulated synaptic currents according to the firing patterns. In delayed firing neurons, NA inhibited both spontaneous excitatory post-synaptic currents (sEPSCs) and spontaneous inhibitory post-synaptic currents (sIPSCs). Hence, NA facilitated sEPSCs and sIPSCs in about a half of regular firing neurons. Bath application of phenylephrine facilitated sEPSCs and sIPSCs, and clonidine inhibited them. These results support the hypothesis of multiple effects of NA in the SPN, and may suggest functional differences among SPN neurons.The sacral parasympathetic nerve controls the functions of pelvic organs such as the urinary bladder, distal end of the colon, and penis. Preganglionic neurons in the sacral parasympathetic nucleus (SPN), which constitutes the pelvic nerve, are located in the lateral edge and/or medial part of laminae V-VII of L6-S1 in the spinal cord of the rat. These neurons receive input from several brainstem nuclei and spinal interneurons. Retrograde tracers such as fast blue and fast DiI are frequently used to distinguish parasympathetic preganglionic neurons (PGNs) within the SPN, because the SPN also contains interneurons, which show similar membrane properties to the PGNs (6). Induced firing of retrogradely labeled SPN neurons in the rat shows several distinct properties (4,19). One type of neurons show delayed firing in response to injected current pulse, and the other type of neurons show regular firing as a response. Various neurotransmitters and chemicals modulate SPN neuronal activities. However, differences in neurochemical modulation of these two types of neurons have not been fully studied. Noradrenaline (NA) is a well-known neurotransmitter in the central nervous system (CNS) and is present in descending pathways from brainstem nuclei A5 and A6 (locus coeruleus) to the spinal cord (27). NAergic modulation of spinal regions has been extensively studied. NA directly depolarizes motor

Activation of alpha‐1 adrenergic receptors increases cytosolic calcium in neurones of the paraventricular nucleus of the hypothalamus

“…In the nTS, an important cardiorespiratory nucleus that contains PVN projecting adrenergic neurones, α 1 ‐AR activation stimulates [Ca 2+ ] i influx, although as oscillations and not the consistent increase we see in PVN neurones . In other central neurones, α 1 ‐AR activation increases action potential discharge and depolarises membranes in the rat medial pontine reticular formation, excites mouse purkinje neurones, induces Ca 2+ oscillations in the anterior pituitary, and increases EPSP frequency and induces membrane depolarisation in the rat sacral autonomic nucleus . The α 1 ‐AR mediated [Ca 2+ ] i increase that we observe fits closely with these other studies.…”

“…In addition, Ca 2+ permeable transient receptor potential cation (TRP) channels 55 and NMDA receptors 56 39 In other central neurones, α 1 -AR activation increases action potential discharge and depolarises membranes in the rat medial pontine reticular formation, 66 excites mouse purkinje neurones, 67 induces Ca 2+ oscillations in the anterior pituitary, 52 and increases EPSP frequency and induces membrane depolarisation in the rat sacral autonomic nucleus. 68 (Figure 6; cAMP to PKA 37 ; and even cPLA 2 activation. 70 We inhibited several parts of the classical α 1 second mes- The effects of NE were not confined to the α 1 -AR mediated increase in baseline [Ca 2+ ] i , we also observed a decrease in voltage-activated (high K + ) Ca 2+ influx that was mimicked by α 2 -AR activation ( Figure 6).…”

“…In mouse PVN neurones, α 2 ‐AR activation inhibited 59% of treated cells, whereas α 1 and β‐ARs excited 35% of treated cells . In several other regions that express inhibitory α 2 ‐ARs, such as Purkinje neurones in the cerebellum and in the sacral autonomic nucleus, α 2 activation leads to an increase in outward current and decrease in EPSP frequency. NE has also been shown to decrease excitability in the SON, a related hypothalamic nucleus .…”