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Central micturition control and urine storage involve a multisynaptic neuronal circuit for the efferent control of the urinary bladder. Electrical stimulation of the lateral preoptic area (LPA) at the level of the decussation of the anterior commissure in cats evokes relaxation of the bladder, whereas ventral stimulation of LPA evokes vigorous contraction. Endogenous Angiotensin-(1-7) [(Ang-(1-7)] synthesis depends on ACE-2, and its actions on binding to Mas receptors, which were found in LPA neurons. We aimed to investigate the Ang-(1-7) actions into the LPA on intravesical pressure (IP) and cardiovascular parameters. The gene and protein expressions of Mas receptors and ACE-2 were also evaluated in the LPA. Angiotensin-(1-7) (5 nmol/μL) or A-779 (Mas receptor antagonist, 50 nmol/μL) was injected into the LPA in anesthetized female Wistar rats; and the IP, mean arterial pressure (MAP), heart rate (HR), and renal conductance (RC) were recorded for 30 min. Unilateral injection of Ang-(1-7) into the LPA increased IP (187.46 ± 37.23%) with peak response at ∼23-25-min post-injection and yielded no changes in MAP, HR, and RC. Unilateral or bilateral injections of A-779 into the LPA decreased IP (-15.88 ± 2.76 and -27.30 ± 3.40%, respectively) and elicited no changes in MAP, HR, and RC. The genes and the protein expression of Mas receptors and ACE-2 were found in the LPA. Therefore, the LPA is an important part of the circuit involved in the urinary bladder control, in which the Ang-(1-7) synthetized into the LPA activates Mas receptors for increasing the IP independent on changes in RC and cardiovascular parameters., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lamy, Cafarchio, do Vale, Antonio, Venancio, de Souza, Maciel, Giannocco, Aronsson and Sato.)

The ventral tegmental area (VTA) underlies motivation and reinforcement of natural rewards. The lateral preoptic area (LPO) is an anterior hypothalamic brain region that sends direct projections to the VTA and to other brain structures known to regulate VTA activity. Here, we investigated the functional connection between the LPO and subpopulations of VTA neurons and explored the reinforcing and valence qualities of the LPO in rats. We found that the LPO and the LPO→VTA pathway inhibit the activity of VTA GABA neurons and have mixed effects on VTA dopamine neurons. Furthermore, we found that the LPO supports operant responding but drives avoidance, and we explored the apparent discrepancy between these two results. Finally, using fiber photometry, we show that the LPO signals aversive events but not rewarding events. Together, our findings demonstrate that the LPO modulates the activity of the VTA and drives motivated behavior and represents an overlooked modulator of reinforcement., (Copyright © 2020 Gordon-Fennell, Gordon-Fennell, Desaivre and Marinelli.)

DiI (1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate) is a lipophilic dye used to research the intracerebral connections of neonatal animals. This dye is most frequently used in the form of dry crystals, but injections of the marker in this state into the mouse brain nuclei, such as MHb (2 cases), LHbM (2 cases), LPA (3 cases) and TS (1 case), clearly revealed excessive lateral diffusion marker into the tissue. Eventually, all the investigated cases except the LPA gave a false positive result. To find the optimal method of marker injection,DiI-kerosene liquid films (3 cases in the MHb); DiI-kerosene gelatinous paste (3 cases in the MHb); injections of insoluble DiI crystals from a solution of 99% dmso (3 cases in the MHb) and 70% ethanol (3 cases in the MHb, 2 cases in the LHbM, 4 cases in the TS) were tested. Injections of DiI in the form of undissolved crystals from a 70% ethanol solution gave a minimal level of side diffusion in all the studied cases. This method of injection is optimal and recommended for use., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The cytology and connections of the lateral habenula (LHb) are reviewed. The habenula is first introduced, after which the cytology of the LHb is discussed mainly with reference to cell types, general topography and descriptions of subnuclei. An overview of LHb afferent connections is given followed by some details about the projections to LHb from a number of structures. An overview of lateral habenula efferent connections is given followed by some details about the projections from LHb to a number of structures. In considering the afferent and efferent connections of the LHb some attention is given to the relative validity of regarding it as a bi-partite structure featuring 'limbic' and 'pallidal' parts. The paper ends with some concluding remarks about the relative place of the LHb in adaptive behaving., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Prolyl carboxypeptidase (PRCP), a serine protease, is widely expressed in the body including liver, lung, kidney and brain, with a variety of known substrates such as plasma prekallikrein, bradykinin, angiotensins II and III, and α-MSH, suggesting its role in the processing of tissue-specific substrates. In the brain, PRCP has been shown to inactivate hypothalamic α-MSH, thus modulating melanocortin signaling in the control of energy metabolism. While its expression pattern has been reported in the hypothalamus, little is known on the distribution of PRCP throughout the mouse brain. This study was undertaken to determine PRCP expression in the mouse brain. Radioactive in situ hybridization was performed to determine endogenous PRCP mRNA expression. In addition, using a gene-trap mouse model for PRCP deletion, X-gal staining was performed to further determine PRCP distribution. Results from both approaches showed that PRCP gene is broadly expressed in the brain., (© 2013 Published by Elsevier B.V.)

Numerous functions have been attributed to the Edinger-Westphal nucleus (EW), including those related to feeding behavior, pain control, alcohol consumption and the stress response. The EW is thought to consist of two parts: one controls accommodation, choroidal blood flow and pupillary constriction, primarily comprising cholinergic cells and projecting to the ciliary ganglion; and the other would be involved in the non-ocular functions mentioned above, comprising peptide-producing neurons and projecting to the brainstem, spinal cord and prosencephalic regions. Despite the fact that the EW is well known, its connections have yet to be described in detail. The aim of this work was to produce a map of the hypothalamic sources of afferents to the EW in the rat. We injected the retrograde tracer Fluoro-Gold into the EW, and using biotinylated dextran amine, injected into afferent sources as the anterograde control. We found retrogradely labeled cells in the following regions: subfornical organ, paraventricular hypothalamic nucleus, arcuate nucleus, lateral hypothalamic area, zona incerta, posterior hypothalamic nucleus, medial vestibular nucleus and cerebellar interpositus nucleus. After injecting BDA into the paraventricular hypothalamic nucleus, lateral hypothalamic area and posterior hypothalamic nucleus, we found anterogradely labeled fibers in close apposition to and potential synaptic contact with urocortin 1-immunoreactive cells in the EW. On the basis of our findings, we can suggest that the connections between the EW and the hypothalamic nuclei are involved in controlling stress responses and feeding behavior., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Forebrain neuronal circuits containing hypocretin-1 (hcrt-1) and norepinephrine (NE) are important components of central arousal-related processes. Recently, these two systems have been shown to have an overlapping distribution within the bed nucleus of the stria terminalis (BST), a limbic structure activated by stressful challenges, and which functions to adjust arterial pressure (AP) and heart rate (HR) to the stressor. However, whether hcrt-1 and NE interact in BST to alter cardiovascular function is unknown. Experiments were done in urethane-α-chloralose anesthetized, paralyzed, and artificially ventilated male Wistar rats to investigate the effect of hcrt-1 and NE on the cardiovascular responses elicited by l-glutamate (Glu) stimulation of BST neurons. Microinjections of hcrt-1, NE or tyramine into BST attenuated the decrease in AP and HR to Glu stimulation of BST. Additionally, combined injections of hcrt-1 with NE or tyramine did not elicit a greater attenuation than either compound alone. Furthermore, injections into BST of the α2-adrenergic receptor (α2-AR) antagonist yohimbine, but not the α1-AR antagonist 2-{[β-(4-hydroxyphenyl)ethyl]aminomethyl}-1-tetralone hydrochloride, blocked both the hcrt-1 and NE-induced inhibition of the BST cardiovascular depressors responses. Finally, injections into BST of the GABAA receptor antagonist bicuculline, but not the GABAB receptor antagonist phaclofen, blocked the hcrt-1 and NE attenuation of the BST Glu-induced depressor and bradycardia responses. These data suggest that hcrt-1 effects in BST are mediated by NE neurons, and hcrt-1 likely acts to facilitate the synaptic release of NE. NE neurons, acting through α2-AR may activate Gabaergic neurons in BST, which in turn through the activation of GABAA receptors inhibit a BST sympathoinhibitory pathway. Taken together, these data suggest that hcrt-1 pathways to BST through their interaction with NE and Gabaergic neurons may function in the coordination of cardiovascular responses associated with different behavioral states., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)