Mechanisms of memory formation and consolidation in hippocampal and cortical pyramidal mouse neurons

The roles of hippocampus and cortex in recent and remote memory processing is well assessed and the association of experience-dependent behavioural modifications with hippocampal and anterior cingulate cortical (ACC) neuron morphological changes at different time points after contextual fear conditioning has been characterised. Although the association between such morphological modifications and biochemical changes related deserves further characterisation. Here, we have previously observed that during the formation of recent contextual fear memory, hippocampal CA1 neurons display morphological changes in parallel with rapid accumulation of EphrinB2, a cell adhesion factor known, in association with its receptor(s), to influence synaptic plasticity and the dynamics of dendritic spines. To investigate whether this process may represent a general marker of induced neuronal plasticity, we studied the conversion of recent -to-remote memory, which ultimately depends on an increase in dendritic spine number of pyramidal neurons of the anterior cingulate cortex (ACC), by analysing the effect of contextual fear conditioning on EphrinB2 levels in these neurons. To this end, we determined dendritic complexity and EphrinB2 levels 24 hours (recent), 7 days (imtermediate) and 36 days (remote) after conditioning in C57BL/6N mice. We observed that EphrinB2 accumulation parallels the increase in spine density of CA1 neurons of conditioned mice, at the recent and intermediate time point, subsequently decreasing at the remote time point. In addition, a similar parallel pattern was observed for neuronal EphrinB2 levels and dendritic complexity in the ACC, which were both increased at the remote time point. The increase in EphrinB2 levels observed in the hipppocampus 24 hr post conditioning and in the ACC 36 days after was prevented by post-training anisomycin treatment. On the contrary, late anisomycin treatmen (24 days post conditioning) didn't prevent EphrinB2 increase in the cortex. These results suggest that accumulation of EphrinB2 is involved in memory-associated cellular modifications detected in both the hippocampus and ACC, and may therefore represent a more general biochemical marker of conditioning-induced neuronal rearrangements

Mechanisms of memory formation and consolidation in hippocampal and cortical pyramidal mouse neurons

The roles of hippocampus and cortex in recent and remote memory processing is well assessed and the association of experience-dependent behavioural modifications with hippocampal and anterior cingulate cortical (ACC) neuron morphological changes at different time points after contextual fear conditioning has been characterised. Although the association between such morphological modifications and biochemical changes related deserves further characterisation. Here, we have previously observed that during the formation of recent contextual fear memory, hippocampal CA1 neurons display morphological changes in parallel with rapid accumulation of EphrinB2, a cell adhesion factor known, in association with its receptor(s), to influence synaptic plasticity and the dynamics of dendritic spines. To investigate whether this process may represent a general marker of induced neuronal plasticity, we studied the conversion of recent -to-remote memory, which ultimately depends on an increase in dendritic spine number of pyramidal neurons of the anterior cingulate cortex (ACC), by analysing the effect of contextual fear conditioning on EphrinB2 levels in these neurons. To this end, we determined dendritic complexity and EphrinB2 levels 24 hours (recent), 7 days (imtermediate) and 36 days (remote) after conditioning in C57BL/6N mice. We observed that EphrinB2 accumulation parallels the increase in spine density of CA1 neurons of conditioned mice, at the recent and intermediate time point, subsequently decreasing at the remote time point. In addition, a similar parallel pattern was observed for neuronal EphrinB2 levels and dendritic complexity in the ACC, which were both increased at the remote time point. The increase in EphrinB2 levels observed in the hipppocampus 24 hr post conditioning and in the ACC 36 days after was prevented by post-training anisomycin treatment. On the contrary, late anisomycin treatmen (24 days post conditioning) didn't prevent EphrinB2 increase in the cortex. These results suggest that accumulation of EphrinB2 is involved in memory-associated cellular modifications detected in both the hippocampus and ACC, and may therefore represent a more general biochemical marker of conditioning-induced neuronal rearrangements

The combined therapy myo-inositol plus d-chiro-inositol, rather than d-chiro-inositol, is able to improve IVF outcomes: results from a randomized controlled trial

The present study aims to investigate the effects of the combined therapy myo-inositol (MI) plus d-chiro-inositol (DCI) or d-chiro-inositol treatment in oocyte quality. Polycystic ovary syndrome (PCOS) women undergoing IVF-ET were treated with myo-inositol combined with d-chiro-inositol in the physiological ratio (1.1 g myo-inositol plus 27.6 mg of d-chiro-inositol; INOFOLICA (R) combi Lo.Li.pharma) or d-chiro-inositol alone (500 mg; Interquim, s.a., Barcelona, Spain) to evaluate the umber of morphological mature oocytes, total International Units (IU) of recombinant FSH administered and the number of grade 1 embryos. The data clearly showed that only the combined therapy was able to improve oocyte and embryo quality, as well as pregnancy rates, in PCOS women undergoing IVF-ET. The present paper further supports the hypothesis that MI plays a crucial role in the ovary in PCOS women. In particular, due to the physiological role played by MI and DCI, the combined therapy should represent a better choice

Contextual learning increases dendrite complexity and EphrinB2 levels in hippocampal mouse neurons

Although the role of hippocampus in memory processing is well assessed, an association of experience-dependent behavioural modifications with hippocampal neuron morphological and biochemical changes deserves further characterisation. Here, we present evidence of dendritic alterations together with rapid accumulation of EphrinB2, a factor known to influence cell plasticity, in pyramidal neurons of the CA1 area of mouse hippocampus, during the formation of recent contextual fear memory. Male C57BL/6N mice exhibited a robust fear response 24 h after contextual and cued fear conditioning. At this time and in the absence of the memory test, conditioned mice showed morphological alterations in hippocampal and lateral amygdala neurons. Western blot analysis of extracts from conditioned but not pseudoconditioned or naive mice showed a specific increase in the amount of EphrinB2 in the hippocampus but not the cortex. However, levels of EphA4 receptor, known to interact trans-synaptically with EphrinB2, did not change upon conditioning in extracts from the same structures. Finally, immunohistochemical analysis of the hippocampus and amygdala of conditioned mice showed increased levels of EphrinB2 in pyramidal neurons of the CM area, when compared to pseudoconditioned and control mice. Such increase was not observed in other hippocampal areas or the amygdala. These results suggest that rapid accumulation of EphrinB2 in hippocampal CA1 neurons is involved in the behavioural and cellular modifications induced by contextual fear conditioning. A similar mechanism does not appear to occur in lateral amygdala neurons, in spite of the robust behavioural and cellular modifications induced in such structure by cued fear conditioning. (C) 2011 Elsevier B.V. All rights reserved

Dendritic spine density and EphrinB2 levels of hippocampal and anterior cingulate cortex neurons increase sequentially during formation of recent and remote fear memory in the mouse

Memory consolidation is a dynamic process that involves a sequential remodeling of hippocampal–cortical circuits. Although synaptic events underlying memory consolidation are well assessed, fine molecular events controlling this process deserve further characterization. To this aim, we challenged male C57BL/6N mice in a contextual fear conditioning (CFC) paradigm and tested their memory 24 h, 7 days or 36 days later. Mice displayed a strong fear response at all time points with an increase in dendritic spine density and protein levels of the cell adhesion factor EphrinB2 in CA1 hippocampal neurons 24 h and 7 days post conditioning (p.c.), and in anterior cingulate cortex (ACC) neurons 36 days p.c. We then investigated whether the formation of remote memory and neuronal modifications in the ACC would de- pend on p.c. protein synthesis in hippocampal neurons. Bilateral intrahippocampal infusions with the protein synthesis inhibitor anisomycin administered immediately p.c. decreased fear response, neuronal spine growth and EphrinB2 protein levels of hippocampal and ACC neurons 24 h and 36 days p.c., respectively. Anisomycin infusion 24 h p.c. had no effects on fear response, increase in spine density and in EphrinB2 protein levels in ACC neurons 36 days p.c. Our results thus confirm that early but not late p.c. hippocampal protein synthesis is necessary for the formation of remote memory and provide the first evidence of a possible involvement of EphrinB2 in neuronal plasticity in the AC

Improvement of mouse embryo quality by myo-inositol supplementation of IVF media

Myo-inositol (myoIns) has a positive role in mammalian development and human reproduction. Since experiments on farming species suggest a similar role in preimplantation development, we evaluated the hypothesis that the inclusion of myoIns in human embryo culture media would produce an increase in embryo quality in IVF cycles, using the mouse embryo assay. To determine the effect of myoIns on completion of preimplantation development in vitro, one-cell embryos of the inbred C57BL/6N mouse strain were produced by ICSI, cultured in human fertilization media in the presence of myoIns (myoIns+) or in its absence (myoIns-) and evaluated morphologically. Daily progression through cleavage stages, blastocyst production and expansion and blastomere number at 96 hours post fertilization were assessed. Compared to myoIns- embryos, myoIns+ embryos displayed a faster cleavage rate and by the end of preimplantation development, the majority of myoIns+ blastocysts was expanded and formed by a higher number of blastomeres. The presence of myoIns resulted in both an increase in proliferation activity and developmental rate of in vitro cultured early mouse embryos, representing a substantial improvement of culture conditions. These data may identify myoIns as an important supplement for human embryo preimplantation culture

Association of TPH2 and dopamine receptor gene polymorphisms with obsessive-compulsive symptoms and perfectionism in healthy subjects

Obsessive–compulsive disorder (OCD) has a multifactorial genetic basis, resulting from the action of several genes and environmental factors. To extend information on the genetics of this disorder, we examined an Italian population sample composed of 72 healthy graduate or undergraduate students of Sapienza University of Rome for association of OC symptoms, perfectionism, and personality traits, with known polymorphisms of tryptophan hydroxylase 2 (TPH2), serotonin transporter (5-HTT) and receptor 5-HT2A, dopamine receptors DRD2, DRD3 and DRD4. Results obtained may contribute to pinpoint TPH2, DRD2 and DRD3 as vulnerability factors in specific behavioral/psychopathological dimensions and represent a further step in the definition of phenotypic OC/perfectionistic behaviors of genetic relevance, ready to be further investigated in other populations