Leptin influences the excitability of area postrema neurons.

The area postrema (AP) is a circumventricular organ with important roles in central autonomic regulation. This medullary structure has been shown to express the leptin receptor and has been suggested to have a role in modulating peripheral signals, indicating energy status. Using RT-PCR, we have confirmed the presence of mRNA for the leptin receptor, ObRb, in AP, and whole cell current-clamp recordings from dissociated AP neurons demonstrated that leptin influenced the excitability of 51% (42/82) of AP neurons.

Glycemic state regulates melanocortin, but not nesfatin-1, responsiveness of glucose-sensing neurons in the nucleus of the solitary tract.

The nucleus of the solitary tract (NTS) is a medullary integrative center with critical roles in the coordinated control of energy homeostasis. Here, we used whole cell current-clamp recordings on rat NTS neurons in slice preparation to identify the presence of physiologically relevant glucose-sensing neurons. The majority of NTS neurons (n = 81) were found to be glucose-responsive, with 35% exhibiting a glucose-excited (GE) phenotype (mean absolute change in membrane potential: 9.

Cellular actions of nesfatin-1 on hypothalamic and medullary neurons.

The present review summarizes the current understanding of the neuronal activation patterns induced by nesfatin-1 in both the hypothalamus and the brainstem, as well as the physiological outcomes caused by the activation of these neuronal populations. Studies using cFos measurements, Ca(2+) imaging techniques, electrophysiological recordings, and microinjections have led to the identification of the paraventricular nucleus, arcuate nucleus, lateral and ventromedial hypothalamic areas, as well as medullary centers such as the nucleus of the solitary tract and dorsal motor nucleus of the vagus as targets of central nesfatin-1 actions on food intake, cardiovascular function, stress responses, and glucose homeostasis.

Circumventricular organs: targets for integration of circulating fluid and energy balance signals?

The subfornical organ (SFO), as one of the sensory circumventricular organs (CVOs), is among the only central nervous system structures which interfaces directly with circulating substances that do not cross the blood brain barrier. Here we describe a growing literature showing that circulating indicators of cardiovascular (angiotensin II, osmolarity, calcium, sodium) and metabolic (adiponectin, amylin, glucose, ghrelin, leptin) statuses influence the excitability of single SFO neurons. Single cell electrophysiological studies from our laboratory have demonstrated excitatory effects of angiotensin II on individual SFO neurons, and changes in angiotensin II receptor expression in this CVO in hypertensive states emphasize the dynamic contribution of SFO neurons to the regulation of fluid balance.

Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function.

Nesfatin-1 has been identified as one of the most potent centrally acting anorexigenic peptides, and it has also been shown to play important roles in the control of cardiovascular function. In situ hybridization and immunohistochemical studies have revealed the expression of nesfatin-1 throughout the brain and, in particular, in the medullary autonomic gateway known as the nucleus of the solitary tract (NTS). The present study was thus undertaken to explore the cellular correlates and functional roles of nesfatin-1 actions in the medial NTS (mNTS).

The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry.

Netrins are guidance cues involved in neural connectivity. We have shown that the netrin-1 receptor DCC (deleted in colorectal cancer) is involved in the functional organization of the mesocorticolimbic dopamine (DA) system. Adult mice with a heterozygous loss-of-function mutation in dcc exhibit changes in indexes of DA function, including DA-related behaviors.

Peri-pubertal emergence of UNC-5 homologue expression by dopamine neurons in rodents.

Puberty is a critical period in mesocorticolimbic dopamine (DA) system development, particularly for the medial prefrontal cortex (mPFC) projection which achieves maturity in early adulthood. The guidance cue netrin-1 organizes neuronal networks by attracting or repelling cellular processes through DCC (deleted in colorectal cancer) and UNC-5 homologue (UNC5H) receptors, respectively. We have shown that variations in netrin-1 receptor levels lead to selective reorganization of mPFC DA circuitry, and changes in DA-related behaviors, in transgenic mice and in rats.

Dexamethasone treatment of post-MI rats attenuates sympathetic innervation of the infarct region.

Sympathetic fiber innervation of the damaged region following injury represents a conserved event of wound healing. The present study tested the hypothesis that impaired scar healing in post-myocardial infarction (post-MI) rats was associated with a reduction of sympathetic fibers innervating the infarct region. In 1-wk post-MI rats, neurofilament-M-immunoreactive fibers (1,116 +/- 250 microm(2)/mm(2)) were detected innervating the infarct region and observed in close proximity to a modest number of endothelial nitric oxide synthase-immunoreactive scar-residing vessels.