Reconsolidation of sucrose instrumental memory in rats: The role of retrieval context
BRAIN RESEARCH
Authors: Piva, Alessandro; Gerace, Elisabetta; Di Chio, Marzia; Padovani, Laura; Paolone, Giovanna; Pellegrini-Giampietro, Domenico E.; Chiamulera, Cristiano
Abstract
Memory reconsolidation enables the update of a previously consolidated memory trace after its reactivation. Although Pavlovian memory reconsolidation has been widely demonstrated, instrumental memory re consolidation is still debated. The most critical issue on instrumental memory reconsolidation findings have mainly been linked to the presence of specific boundary conditions for reactivation, for instance contextual parameters. In this study, we investigated the role of the spatial context on molecular markers of sucrose instrumental memory reactivation. Following withdrawal, rats previously conditioned to sucrose self-administration underwent either instrumental memory retrieval or no-retrieval in the conditioned context (Context A, AA condition) or in a modified version of the conditioned context (Context B, AB condition). Two hours later, the level of GluA1 and GluN2B receptors, Zif268 and phosphorylated-rpS6 (rpS6P) was measured in key brain areas for memory reactivation. Retrieval in Context A significantly increased GluA1Rs and GluN2BRs in amygdala compared to no-retrieval, indicating that memory successfully reactivated and destabilized. Moreover, Zif268 level was significantly increased after retrieval in Context A in the nucleus accumbens shell, central and basolateral amygdala but not in the hippocampus, while retrieval in Context B significantly increased Zif268 level in all brain areas. On the other hand, rpS6P level was increased in the nucleus accumbens shell and central amygdala, but decreased in the hippocampus, after retrieval in Context A, while retrieval in Context B did not change rpS6P level in brain areas, except for a small but significant decrease in hippocampus. While the increase of Zif268 level indicated that memory reactivation has been triggered in both the conditions, the lack of change in rpS6P levels after retrieval in Context B - in particular in the central amygdala - suggests that the reconsolidation process could not occur after memory reactivation in a context different from the conditioned one.
Muscle protein synthesis, mTORC1/MAPK/Hippo signaling, and capillary density are altered by blocking of myostatin and activins
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Authors: Hulmi, Juha J.; Oliveira, Bernardo M.; Silvennoinen, Mika; Hoogaars, Willem M. H.; Ma, Hongqiang; Pierre, Philippe; Pasternack, Arja; Kainulainen, Heikki; Ritvos, Olli
Abstract
Hulmi JJ, Oliveira BM, Silvennoinen M, Hoogaars WM, Ma H, Pierre P, Pasternack A, Kainulainen H, Ritvos O. Muscle protein synthesis, mTORC1/MAPK/Hippo signaling, and capillary density are altered by blocking of myostatin and activins. Am J Physiol Endocrinol Metab 304:E41-E50, 2013. First published October 31, 2012; doi:10.1152/ajpendo.00389.2012.-Loss of muscle mass and function occurs in various diseases. Myostatin blocking can attenuate muscle loss, but downstream signaling is not well known. Therefore, to elucidate associated signaling pathways, we used the soluble activin receptor IIb (sActRIIB-Fc) to block myostatin and activins in mice. Within 2 wk, the treatment rapidly increased muscle size as expected but decreased capillary density per area. sActRIIB-Fc increased muscle protein synthesis 1-2 days after the treatment correlating with enhanced mTORC1 signaling (phosphorylated rpS6 and S6K1, r = 0.8). Concurrently, increased REDD1 and eIF2Be protein contents and phosphorylation of 4E-BP1 and AMPK was observed. In contrast, proangiogenic MAPK signaling and VEGF-A protein decreased. Hippo signaling has been characterized recently as a regulator of organ size and an important regulator of myogenesis in vitro. The phosphorylation of YAP (Yes-associated protein), a readout of activated Hippo signaling, increased after short-and longer-term myostatin and activin blocking and in exercised muscle. Moreover, dystrophic mdx mice had elevated phosphorylated and especially total YAP protein content. These results show that the blocking of myostatin and activins induce rapid skeletal muscle growth. This is associated with increased protein synthesis and mTORC1 signaling but decreased capillary density and proangiogenic signaling. It is also shown for the first time that Hippo signaling is activated in skeletal muscle after myostatin blocking and exercise and also in dystrophic muscle. This suggests that Hippo signaling may have a role in skeletal muscle in various circumstances.