Biomedical subjects

Nathalie Picard

Publications and source records attributed to Nathalie Picard.

4 recordsLinked to original sources

PubMed2006

Skill representation in the primary motor cortex after long-term practice.

The acquisition of motor skills can lead to profound changes in the functional organization of the primary motor cortex (M1). For example, performance of movement sequences after prolonged practice is associated with an expansion of the effector representation in M1. Paradoxically, there is little evidence that the activity of M1 neurons reflects acquired skills, especially sequences of movements. We examined the activity of M1 neurons during skilled movement sequences in macaques trained to successively hit targets on a monitor. The targets appeared either pseudorandomly (Random mode) or in one of two repeating sequences (Repeating mode). With practice, response times for repeating sequences substantially declined and the monkeys performed the task predictively. Highly trained animals retained the acquired skill after long gaps in practice. After >2 yr of training, 40% of M1 neurons were differentially active during the two task modes. Variations in movement kinematics did not fully explain the task-dependent modulation of neuron activity. Differentially active neurons were more strongly influenced by task mode than by kinematics. Our results suggest that practice sculpts the response properties of M1 neurons. M1 may be a site of storage for the internal representation of skilled sequential movements.

Animals↗

PubMed2006

The hormonal response of estrogen receptor beta is decreased by the phosphatidylinositol 3-kinase/Akt pathway via a phosphorylation-dependent release of CREB-binding protein.

The hormonal response of estrogen receptors (ER) alpha and ERbeta is controlled by a number of cofactors, including the general transcriptional coactivator CREB-binding protein (CBP). Growing evidence suggests that specific kinase signaling events also modulate the formation and activity of the ER coactivation complex. Here we show that ERbeta activity and target gene expression are decreased upon activation of ErbB2/ErbB3 receptors despite the presence of CBP. This inhibition of ERbeta involved activation of the phosphatidylinositol 3-kinase/Akt pathway, abrogating the potential of CBP to facilitate ERbeta response to estrogen. Such reduced activity was associated with an impaired ability of ERbeta to recruit CBP upon activation of Akt. Mutation of serine 255, an Akt consensus site contained in the hinge region of ERbeta, prevented the release of CBP and rendered ERbeta transcriptionally more responsive to CBP coactivation, suggesting that Ser-255 may serve as a regulatory site to restrain ERbeta activity in Akt-activated cells. In contrast, we found that CBP intrinsic activity was increased by Akt through threonine 1872, a consensus site for Akt in the cysteine- and histidine-rich 3 domain of CBP, indicating that such enhanced transcriptional potential of CBP did not serve to activate ERbeta. Interestingly, nuclear receptors sharing a conserved Akt consensus site with ERbeta also exhibit a reduced ability to be coactivated by CBP, whereas others missing that site were able to benefit from the activation of CBP by Akt. These results therefore outline a regulatory mechanism by which the phosphatidylinositol 3-kinase/Akt pathway may discriminate nuclear receptor response through coactivator transcriptional competence.

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PubMed2006

The circadian regulation of Presenilin-2 gene expression.

Circadian rhythms are generated by a molecular clock composed of clock genes and their protein products. Other genes are regulated in a rhythmic way by this molecular clockwork, but are not themselves constituents of the clock. This study shows that one of these clock-controlled genes encodes the signalling protein Presenilin-2. Indeed, evidence is presented that the promoter of the mouse Presenilin-2 gene is bound and activated by CLOCK and BMAL1, transcription factors of the mammalian circadian clock. Quantification of Presenilin-2 RNA shows that its expression is non-rhythmic in many peripheral tissues (heart, muscle, kidney, spleen, and thymus). Note, though, that careful analysis of the liver data shows that Presenilin-2 RNA exists in distinct isoforms in this tissue, and that rhythmicity is restricted to only a subset of these RNA isoforms. These data indicate a unique mode of regulation of Presenilin-2 transcripts, the circadian control of which appears to happen at the transcriptional and post-transcriptional levels.

ARNTL Transcription Factors↗

PubMed2003

Activation of the supplementary motor area (SMA) during performance of visually guided movements.

The supplementary motor area (SMA) has long been thought to have a special role in the internal generation of complex movements. Yet, a number of recent functional imaging studies indicate that the SMA is activated during the execution of simple movements guided by sensory cues. The extent of participation of the cingulate motor areas in visually guided movements also is unclear. To explore these issues we used the 2-deoxyglucose (2DG) technique to measure functional activation in the motor areas on the medial wall of the hemisphere in monkeys trained to perform visually guided reaching movements to randomly presented targets. This approach enabled us to make precise comparisons between sites of activation and the location of specific premotor areas on the medial wall of the hemisphere. We found that the SMA was strongly activated during reaching to different visual targets. Indeed, its activation was comparable to that of the primary motor cortex (M1). In contrast, none of the cingulate motor areas displayed significantly increased activation specifically related to arm movements. Our results provide further support for the involvement of the SMA in visually guided movements. Furthermore, our observations suggest that during externally guided reaching, SMA activation is tightly coupled to that of M1, but dissociated from that of the cingulate motor areas.

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