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International audience; Endogenous cannabinoid receptors are widely distributed throughout the CNS, including the brainstem, and modulate a variety of functions, including breathing. In adult rats, activation of cannabinoid 1 receptors has been shown to depress breathing. Here in neonatal mice, we used in vitro electrophysiology, pharmacology, and immunohistochemistry to analyse the central effects of the endocannabinoid anandamide (AEA) on the activity of the medullary respiratory rhythm generator (RRG). First of all, in vitro electrophysiology on medullary preparations has revealed that bath application of AEA (30 μM, 15 min) significantly depressed respiratory activity. Secondly, applying pre-treatments with alpha-1 (Prazosin, 5 μM, 10 min) and alpha-2 (Yohimbine, 5 μM, 10 min) adrenoceptor antagonists prior to AEA application abolished the AEA-induced depression of the RRG. Finally, immunostaining revealed a dense network of fibres positive for the cannabinoid 1 receptor in the ventrolateral medulla (VLM), a region known to contain both the RRG and the modulatory A1/C1 catecholaminergic group. Moreover, cannabinoid 1 receptor positive fibres were found in close apposition with A1/C1 catecholaminergic cells, identified by the presence of tyrosine hydroxylase. In regard of our electrophysiological, pharmacological and immunostaining results, we conclude that AEA has a central depressive effect on the neonatal RRG, probably via the medullary A1/C1 catecholaminergic neurons which are already known to modulate the respiratory rhythm generator.

The prostate gland is a rich source of alpha1-adrenergic receptors (alpha1-ARs). alpha1-AR antagonists are commonly used in the treatment of benign prostatic hyperplasia symptoms, due to their action on smooth muscle cells. However, virtually nothing is known about the role of alpha1-ARs in epithelial cells. Here, by using two human prostate cancer epithelial (hPCE) cell models - primary cells from resection specimens (primary hPCE cells) and an LNCaP (lymph node carcinoma of the prostate) cell line - we identify an alpha1A subtype of adrenergic receptor (alpha1A-AR) and show its functional coupling to plasmalemmal cationic channels via direct diacylglycerol (DAG) gating. In both cell types, agonist-mediated stimulation of alpha1A-ARs and DAG analogues activated similar cationic membrane currents and Ca(2+) influx. These currents were sensitive to the alpha1A-AR antagonists, prazosin and WB4101, and to transient receptor potential (TRP) channel blockers, 2-aminophenyl borate and SK&F 96365. Chronic activation of alpha1A-ARs enhanced LNCaP cell proliferation, which could be antagonized by alpha1A-AR and TRP inhibitors. Collectively, our results suggest that alpha1-ARs play a role in promoting hPCE cell proliferation via TRP channels.

International audience; The piriform cortex (PCx) has a potential role in storage and recall of olfactory information. This study is a first extensive investigation of the spatiotemporal distribution of activity in the PCx induced by learned sensory inputs following conditioning. In a conditioned group, rats chronically implanted with four electrodes in the olfactory bulb were trained to associate the electrical stimulation of a given bulbar electrode with a positive reinforcement, while stimulation of a different electrode predicted a negative reinforcement. In a familiarized group, rats received the same protocol of daily electrical stimulation with no associated reinforcement. At the end of the conditioning or familiarization episode, activity evoked in the PCx was optically mapped using a 144 photodiode array. In the anaesthetized rats, PCx maps were recorded in response to stimulation of each of the four bulbar electrodes using either high (0.5-1 mA) or low (0.1 mA) test current intensities. Low intensity stimulation revealed that conditioning selectively enhanced the probability of occurrence of a signal composed of a single late (56-73 ms) component which occurred almost simultaneously on a large PCx area. In the conditioned group, high intensity stimulation through either of the four electrodes revealed a potentiation of the early (17-30 ms) disynaptic component of the PCx response in the most posterior part of the PCx as well as a homogeneous increase of the late (39-52 ms) component spread over the PCx areas. These data suggest that learning induces synaptic changes at different nodes of the PCx circuitry.

International audience; The selectivity of rat auditory cortex neurons for pure tone frequency was studied during and after ionophoretic application (5-40 nA) of noradrenaline in urethane-anaesthetized rats. The dominant effect induced by noradrenaline was a significant decrease in spontaneous (93/268 cells) and evoked activity (133/268 cells) which outlasted the application. In the whole population of cells (n = 268) the signal-to-noise ratio, computed using as the signal either the mean evoked response or the response at the best frequency, was unchanged during noradrenaline application. It was significantly increased only for cells showing significantly decreased spontaneous activity, and was significantly decreased for cells showing increased spontaneous activity. Frequency selectivity was significantly increased for the whole population during and after noradrenaline application. It was also significantly increased for cells showing significantly decreased evoked activity, and was significantly decreased for cells showing increased evoked activity. The noradrenaline-induced inhibition was not blocked by propranolol (beta antagonist); it was blocked by prazosin (alpha1 antagonist) and partly mimicked by phenylephrine (alpha1 agonist). GABA, which also inhibited spontaneous and evoked activity, slightly increased the signal-to-noise ratio and significant increased frequency selectivity. However, when noradrenaline was ejected in the presence of bicuculline at doses that were able to block GABAergic inhibition, the inhibitory effects of noradrenaline on spontaneous and evoked activity were still observed. The possible function of noradrenaline-induced inhibitions in sensory cortices is briefly discussed.

International audience; Previous studies have suggested that central administration of neuropeptide FF-related peptides may modulate cardiovascular parameters in the rat. In the present study, we investigated the role of dorsal vagal complex neuropeptide FF receptors in the central regulation of cardiovascular parameters. The fate of neuropeptide FF receptors in normal and nodose ganglionectomized rats was investigated using an autoradiographic approach with 125I-[DTyr1, (NMe)Phe3]NPFF as ligand for these receptors. We showed that neuropeptide FF binding sites are preferentially located postsynaptically with respect to the vagal afferent fibers in the nucleus tractus solitarius. Thus, ganglionectomy reduced by only 30% and 17% the density of peptide binding sites in the rostral and caudal regions of this nucleus, respectively. Bilateral microinjection of neuropeptide FF (1 nmol) into the commissural nucleus tractus solitarius produced an increase in blood pressure (+13.8 +/- 0.8 mmHg, n = 6), bradycardia (-29.0 +/- 3.2 bpm) and a significant inhibition (-47.6 +/- 3.1%) of the cardiac component of the baroreceptor reflex. Further studies with doses below 1 nmol indicate that NTS microinjections of the neuropeptide produced a dose-dependent decrease in heart rate. Similar cardiovascular effects were observed after bilateral NTS microinjections of one analog neuropeptide FF receptor agonist, [DTyr1, (NMe)Phe3]NPFF (1 nmol). Pretreatment with prazosin (100 micrograms/kg), an alpha 1-adrenoreceptor antagonist, inhibited the neuropeptide FF-evoked blood pressure effect. In addition, the neuropeptide FF-induced heart rate decrease was abolished by pretreatment with atropine (30 micrograms/kg), a muscarinic receptor antagonist. Taken together, these anatomical and pharmacological data suggest that neuropeptide FF receptors within the nucleus tractus solitarius, preferentially located on the postsynaptic component, are involved in the central reflex regulation of cardiovascular parameters.