Largely shared neural codes for biological and nonbiological observed movements but not for executed actions in monkey premotor areas

The neural processing of others' observed actions recruits a large network of brain regions (the action observation network; AON) in which frontal motor areas are thought to play a crucial role. As the discovery of mirror neurons (MNs) in the ventral premotor cortex, it has been assumed that their activation was conditional upon the presentation of biological rather than nonbiological motion stimuli, supporting a form of direct visuomotor matching. Nonetheless, nonbiological observed movements have rarely been used as control stimuli to evaluate visual specificity, thereby leaving the issue of similarity among neural codes for executed actions and biological or nonbiological observed movements unresolved. Here, we addressed this issue by recording from two nodes of the AON that are attracting increasing interest, namely, the ventrorostral part of the dorsal premotor area F2 and the mesial presupplementary motor area F6 of macaques while they 1) executed a reaching-grasping task, 2) observed an experimenter performing the task, and 3) observed a nonbiological effector moving in the same context. Our findings revealed stronger neuronal responses to the observation of biological than nonbiological movement, but biological and nonbiological visual stimuli produced highly similar neural dynamics and relied on largely shared neural codes, which in turn remarkably differed from those associated with executed actions. These results indicate that, in highly familiar contexts, visuomotor remapping processes in premotor areas hosting MNs are more complex and flexible than predicted by a direct visuomotor matching hypothesis

The physiological dilemma of the high progesterone syndrome in rabbit does

This work focused on the mechanisms that may cause multiple asynchronous ovulations and alter normal ovarian function in order to characterize the high progesterone (P+) syndrome in rabbit does, that, having abnormally high plasma progesterone concentration at the time of insemination, fail to become pregnant. At different luteal stages, at either days 4, 9, or 13 of pseudopregnancy, induced by GnRH injection (d-0), two groups of rabbits (n=5/group) were treated with saline or 0.8 \ub5g GnRH. Blood samples were collected from d-0 to d-26 of pseudopregnancy. At d-4, GnRH injection prolonged (P<0.05) the functional CL life span by 3 to 4 d over that of controls. At d-9, GnRH caused a transient decline (P<0.01) of progesterone for the following 3 d but, thereafter, increased again and remained higher (P<0.01) than controls up to d-26. At d-13, progesterone fell to 1 ng/ml within one day following GnRH, but then gradually increased. Based of these progesterone profiles, it can be argued that, at both mid- and late-luteal phase, GnRH triggered luteolysis and induced ovulation followed by the formation of a new generation of CL. For the in vitro study, CL, collected at days 4, 9, and 13 of pseudopregnancy, were incubated with GnRH, GnRH-antagonist, PLA2 inhibitor, and PLC inhibitor. GnRH decreased (P<0.01) progesterone secretion by d-9 and d-13 CL cultured in vitro; by converse, GnRH antagonist, increased (P<0.01) progesterone release from d-4 CL. Co-incubation of GnRH with GnRH antagonist increased (P<0.01) progesterone release in d-4 CL, but had an opposite effect (P<0.01) on d-9 and d-13 CL. PLC inhibitor reversed the GnRH effects in both d-9 and d-13 CL, while PLA2 inhibitor did not change progesterone release. These data suggest that rabbit CL express a functional receptor for GnRH, likely of type II, that utilizes the PLC post transductional cascade. Luteal FSH-R and LH-R mRNA relative abundances did not differ between d-4 and d-9 CL, but were two- to three-fold (P 640.01) higher, respectively, at d-13. StAR mRNA was highly expressed at d-4 of pseudopregnancy, but then markedly declined (P 640.01) at d-9 and d-13. Taken together, our results show that GnRH triggers i) functional regression when CL acquire luteolytic capacity from d 9 of pseudopregnancy onward, and ii) multiple asynchronous ovulations, thus partly explaining the P+ syndrome associated with the simultaneous coexistence of two population of \u201cfresh\u201d and \u201cold\u201d CL, although not yet the underlying causes

Local and system mechanisms for action execution and observation in parietal and premotor cortices

The action observation network (AON) includes a system of brain areas largely shared with action execution in both human and nonhuman primates. Yet temporal and tuning specificities of distinct areas and of physiologically identified neuronal classes in the encoding of self and others’ action remain unknown. We recorded the activity of 355 single units from three crucial nodes of the AON, the anterior intraparietal area (AIP), and premotor areas F5 and F6, while monkeys performed a Go/No-Go grasping task and observed an experimenter performing it. At the system level, during task execution, F6 displays a prevalence of suppressed neurons and signals whether an action has to be performed, whereas AIP and F5 share a prevalence of facilitated neurons and remarkable target selectivity; during task observation, F5 stands out for its unique prevalence of facilitated neurons and its stronger and earlier modulation than AIP and F6. By applying unsupervised clustering of spike waveforms, we found distinct cell classes unevenly distributed across areas, with different firing properties and carrying specific visuomotor signals. Broadly spiking neurons exhibited a balanced amount of facilitated and suppressed activity during action execution and observation, whereas narrower spiking neurons showed more mutually facilitated responses during the execution of one's own and others’ action, particularly in areas AIP and F5. Our findings elucidate the time course of activity and firing properties of neurons in the AON during one's own and others’ action, from the system level of anatomically distinct areas to the local level of physiologically distinct cell classes

Crosslinked SPEEK membranes: Mechanical, thermal, and hydrothermal properties

The thermal and mechanical behavior, the water uptake (WU), and water diffusion coefficient of sulfonated poly(ether ether ketone) (SPEEK)membranes annealed at 180 degrees C for different times were explored by high-resolution thermogravimetric analysis, mechanical tensile tests, dynamic mechanical analysis, and WU measurements. The mechanical and thermal stability increased with the thermal treatment time, i.e., with the degree of crosslinking. The effect of residual casting solvent, dimethyl sulfoxide (DMSO), on the WU within SPEEK was probed. In presence of residual DMSO, crosslinked SPEEK exhibited higher water sorption at low and medium relative humidity (RH), and lower water sorption at high RH. These membranes have properties well adapted to fuel cell applications

Vasoactive peptides in the luteolytic process activated by PGF2alpha in pseudopregnant rabbits at different luteal stages

To study the role of endothelial factors in luteal function, the dynamic profiles of genes for endothelin 1 (EDN1), its receptor subtypes, EDNRA and EDNRB, and angiotensin converting enzyme (ACE) were examined in corpora lutea (CL) obtained from rabbits on Days 4 and 9 of pseudopregnancy after prostaglandin (PG) 172a analogue (alfaprostol) treatment. The cell type distribution of EDN1 in the ovaries and its mechanisms of actions in vitro and in vivo were also studied. Positive immunostaining for EDN1 was localized in the luteal and endothelial cells, in granulosa cells of the follicles, and in the ovarian epithelium. The basal mRNA levels for EDNRA, EDNRB, and ACE were lower (P <= 0.01) in Day-4 CL than in Day-9 CL, whereas those for EDNi did not differ between these two time-points. On Day 4, the luteal EDN1, EDNRA, EDNRB, and ACE mRNA levels were similarly increased two-fold (P <= 0.01) 1.5 h after alfaprostol injection, and did not show further changes in the subsequent 24 h. On Day 9, alfaprostol challenge transiently up-regulated (P < 0.01) the luteal ACE transcripts at 1.5 h, and those of EDN1 at 1.5 h and 3 h, whereas the EDNRA and EDNR8 transcript levels remained unchanged during the course of luteal regression. EDN1 decreased (P < 0.01) progesterone release and increased (P <= 0.01) PGF2 alpha secretion and NOS activity via the PLC/PKC pathway in Day-9 CL, but not in Day-4 CL, cultured in vitro. EDN1-induced, but not alfaprostol-induced luteolysis, was blocked by cotreatment in vivo with the ACE antagonist captopril. These findings support the hypothesis that PGF2 alpha regulates luteolysis through intraluteal activation of the reninangiotensin/EDN1 systems in CL that have acquired luteolytic competence

Intrinsic direct role of dopamine in the regulation of rabbit (Oryctolagus cuniculus) corpora lutea: in vitro study

Dopamine (DA) is a catecholamine neurotransmitter that is distributed in the brain and also in different peripheral organs. In particular, DA receptors (DR) are expressed in luteal cells of various species, but the intrinsic role of the DA/DRs system on corpora lutea (CL) function is still unclear. The main objectives of the present study were to examine in rabbit CL the gene expression of DRs and DA and their immunolocalization, as well as the in vitro effects of DA on the production of progesterone, PGE2, and PGF2a during early, mid, and late luteal stages of pseudopregnancy. Immunoreactivity and gene expression for DR type 1 (D1R) decreased while that for D3R increased in luteal and blood vessel cells from early to late pseudopregnant stages. DA immunopositivity was evidenced only in luteal cells. DA and D1R agonist increased in vitro release of progesterone and prostaglandin E2 (PGE2) by early CL, whereas DA and D3R agonist decreased progesterone and increased PGF2a in vitro release by mid and late CL. These results provide evidence that the DA/DR system exerts a dual modulatory function in controlling the lifespan of CL: the DA/D1R is luteotrophic, while the DA/D3R is luteolytic. The present data shed new light on the physiological mechanisms regulating luteal activity that might improve our ability to optimize reproductive efficiency in mammal species, including humans

Aglepristone (RU534) administration to non-pregnant bitches in the mid-luteal phase induces early luteal regression

The effect of the antiprogestagen aglepristone (10 mg/kg bw), administered at days 29 and 30 following the estimated day of LH surge (day 0), on corpora lutea (CL) function was examined during the diestrus phase of non-pregnant bitches. Aglepristone shortened (P < 0.01) the luteal phase and complete luteolysis (progesterone <2 ng/mL) was observed at days 40.8 ± 3.5 and 71.5 ± 4.6 (means ± SD; n = 9/group) in treated and control bitches, respectively. Peripheral estradiol-17β concentrations declined from 91.5 ± 14.3 pg/mL at day 9 to 50 pg/mL at day 18, remaining at approximately the same levels thereafter in both treated and control bitches. Intraluteal in vitro synthesis of progesterone and estradiol-17β released by CL explanted at day 38 from control bitches (511.9 ± 285.6 and 40.7 ± 17.2 pg/mg protein, respectively) did not differ from that of treated. From day 38, intraovarian hemodynamic variables (arterial blood flow, systolic peak, and end-diastolic velocities), monitored by color-coded and pulsed Doppler, decreased more steeply (P < 0.01) in aglepristone-treated (n = 4) than in control (n = 4) bitches, whereas the resistance index increased (P < 0.01) in treated animals. All the blood flow parameters were undetectable at 60 ± 3.6 and 68 ± 2.0 days (medians ± SD) after LH peak in treated and control bitches, respectively. In conclusion, aglepristone administration to dogs during the mid-luteal phase markedly accelerates the luteolytic process which is accompanied by a parallel decline in ovarian blood flow supply with a shift from approximately 8 to 10 days

Expression of luteal estrogen receptor, interleukin-1, and apoptosis-associated genes after PGF2α administration in rabbits at different stages of pseudopregnancy

The dynamic expression for estrogen receptor subtype-1 (ESR1), interleukin-1beta (IL1B), and apoptosis-associated genes, as well as nitric oxide synthase activity, were examined in corpora lutea (CL) of rabbits after prostaglandin F(2alpha) (PGF(2alpha)) administration on either day 4 or day 9 of pseudopregnancy. By reverse transcriptase polymerase chain reaction, the steady-state level of ESR1 transcript was lower (P < 0.01) and that of anti-apoptotic B-cell CLL/lymphoma 2 (BCL2) -like 1 (BCL2L1) was greater in day 4 (P < 0.01) than in day 9 CL. Western blot analysis revealed that BCL2-associated X protein (BAX) abundance was greater in day 4 (P < 0.01) than in day 9 CL, whereas BCL2L1 protein was undetectable at both luteal stages. After PGF(2alpha), ESR1 transcript decreased (P < 0.01) in day 9 CL, whereas IL1B mRNA showed a transitory increase (P < 0.01) at both stages. The pro-apoptotic tumor protein p53 (TP53) gene had diminished (P < 0.01) on day 4 and on day 9 after a transitory increase (P < 0.01), whereas the BAX/BCL2L1 expression ratio increased (P < 0.01) in day 9 CL 24 h after treatment. Following PGF(2alpha), TP53 protein increased (P < 0.01) at both luteal stages, and BAX decreased (P < 0.01) in day 4 CL but increased (P < 0.01) 24 h later in day 9 CL; BCL2L1 became detectable 6 h later in day 4 CL. Nitric oxide synthase activity temporarily increased (P < 0.01) following PGF(2alpha). These findings suggest that PGF(2alpha) regulates luteolysis by ESR1 mRNA down-regulation and modulation of pro- and anti-apoptotic pathways in CL that have acquired a luteolytic capacity

Regolazione della funzione e regressione luteale nel coniglio

La funzione principale del corpo luteo (CL) \ue8 la produzione del progesterone determinante per conseguire e portare a termine la gravidanza. Nel coniglio, i meccanismi che controllano lo sviluppo dei CL, la funzione secretoria e la regressione coinvolgono diversi fattori intra- ed extra-ovarici con azione luteotropa e luteolitica tra cui gli estrogeni e la prostaglandina F2 (PGF2 ). La loro azione risultante \ue8 tuttavia mediata da una complessa serie di interazioni che coinvolgono meccanismi in cui un ruolo non trascurabile \ue8 svolto da fattori ad azione autocrina e/o paracrina, emersi nel corso degli anni, quali principali regolatori dell\u2019attivit\ue0 luteale, tra i quali: citochine (es. interleuchine, leptina), peptidi vasoattivi (es. ossido nitrico, endotelina) e fattori legati all\u2019apoptosi (es. membri della famiglia BCL2 e TP53). Il CL neoformato sembra essere resistente all\u2019azione della PGF2 . La competenza luteolitica all\u2019azione della PGF2 aumenta progressivamente con lo sviluppo del CL e viene pienamente acquisita dal 9\ub0 giorno di pseudogravidanza. I risultati riassunti in questo lavoro con differenti approcci metodologici, testimoniano che, anche nei CL apparentemente refrattari all\u2019azione della PGF2 , esiste una intensa attivit\ue0 molecolare determinata da questa luteolisina. I dati ottenuti approfondiscono meccanismi biologici che sono di estremo interesse nel campo della fisiologia ovarica ma che stanno alla base anche della patologia riproduttiva.The main function of corpus luteum (CL) is the production of progesterone which is necessary for achieving and maintaining a successful pregnancy. In rabbits, the mechanisms controlling luteal development and secretory function as well as luteal regression involve different intra- and extra-ovarian factors with luteotrophic and luteolytic actions, including estrogens and prostaglandin F2 (PGF2 ). These factors act by complex interactions involving autocrine and/or paracrine mechanisms. Over the past few years, they emerged as important regulators of luteal activity: cytokines (e.g. interleukins, leptin), vasoactive peptide (e.g. endothelin, nitric oxide) and apoptotic factors (e.g. BCL2 family members and TP53). The newly formed CL appear to resist the luteolytic action of PGF2 . The acquisition of luteal competency to PGF2 increases progressively with the CL development and, at day 9 of pseudopregnancy, they are fully responsive. The results here summarized show that in CL apparently resistant to the luteolytic action of PGF2 exists an intense molecular activity induced by this luteolysine. The data obtained with different methodological approaches provide further details on biological mechanisms that are relevant in the field of ovarian physiology, as well as in that of reproductive pathology