The Generation of Complex Reaches

The study of motor cortex (dorsal premotor cortex and primary motor cortex) has been greatly aided by the development of a conceptual paradigm that has emerged over the past decade. In contrast to established frameworks, which view neural activity within motor cortex as a representation of particular movement parameters, the ‘dynamical systems paradigm’ posits that motor cortex is best understood via the low-dimensional neural processes that allow the generation of motor commands. This framework largely evolved from, and has been most successfully applied to, simple reaching tasks, where the sequential stages of movement generation are largely separated in time – motor cortex absorbs an input that specifies the identity of the upcoming reach, a second input initiates the movement, and strong, autonomous dynamics generate time-varying motor commands. However, while the dynamical systems paradigm has provided a useful scaffolding for interrogating motor cortex, our understanding of the mechanisms that generate movement is still evolving, and many questions remain unanswered. Prior work has established that the neural processes within motor cortex that generate descending commands are initiated by a large, condition-invariant input. But are movements made under different behavioral contexts initiated via the same mechanisms? Lesion studies suggest that the generation of so-called ‘self-initiated movements’ is uniquely dependent on the supplementary motor area (SMA), a premotor region immediately upstream of motor cortex. In contrast, SMA is thought to be less critical for generating externally-cued movements. To characterize the degree to which SMA is able to impact movement initiation across behavioral contexts, we trained two monkeys to make reaches that were either internally or externally cued. On a subset of trials, we disrupted activity within SMA via microstimulation and asked how this perturbation impacted the monkeys’ behavior. Surprisingly, we found that the effect of stimulation was largely preserved across contexts; the behavioral effects of stimulation could be explained by a simple model in which a context-invariant, time-varying kernel multiplicatively altered the odds of movement initiation. These results suggest that SMA is able to impact movement initiation across behavioral contexts. The question of how sequences of discrete actions are generated has been investigated for over one hundred years. It is commonly thought that once a given sequence (particularly a rapid sequence) becomes well-learned, individual actions that were once produced separately become ‘merged’, such that multiple actions are generated as a single, holistic unit. But what does it mean to generate multiple actions as a single unit? The dynamical systems paradigm offers the ability to translate this notion into specific predictions about the timing and structure of neural activity within motor cortex during sequence production. Importantly, it also offers predictions for the alternative hypothesis – that motor cortex generates the component actions of a sequence independently. To determine whether the production of rapid sequences requires motor cortex to merge multiple actions into a single ‘movement’, we trained monkeys to make sequences of two reaches. Surprisingly, we found that the same set of neural events are used to produce rapid sequences and isolated reaches. Rather than merging individual actions into a single unit, motor cortex generated rapid sequences by overlapping the neural activity related to reach preparation and execution. These results demonstrate that the performance of extremely fast, well-learned movement sequences does not require motor cortex to implement a sequence-specific strategy; the same neural motif that produces a simple reach can also generate movement sequences

Neutron imaging with fission and thermal neutrons at NECTAR at MLZ

The instrument NECTAR is located at beam port SR10 of the neutron source FRM II at the Heinz Maier-Leibnitz Zentrum (MLZ). With a pair of moveable uranium plates placed in front of the entrance window of the beam tube, a fission neutron spectrum with a mean energy of 1.9 MeV can be used for neutron imaging applications. Via remote control these plates can be removed and a thermal neutron spectrum (mean energy at 28 meV) gets available for experiments. While the fission neutron spectrum is regularly used, some upgrades of the instrument are necessary to make the thermal neutron spectrum routinely available for user experiments. This includes additional equipment like a new sample stage and a second detector system foreseen to extend the capabilities of NECTAR. The current state of the instrumentation and necessary changes for the future thermal beam option and its usage for standard user experiments will be presented. First measurements were carried out with a temporary flight tube installed and a compact detector (510 mm × 180 mm x 180 mm) for thermal neutrons with a spatial resolution in the range of 100 μm. The feasibility of the thermal beam option could already be verified at an L/D ratio of 240 and a thermal neutron flux of 7.92·106 cm−2 s−1. The thermal neutron beam option adds a pure thermal neutron spectrum – Maxwell spectrum originating from the moderator without alteration by a secondary source or converter – to the energy ranges available for neutron imaging at MLZ instruments. It also offers a unique possibility to combine two quite different neutron energy ranges at a single instrument including their respective advantages. The thermal neutron beam option is funded by BMBF in the frame of research project 05K16VK3

Neural activity during a simple reaching task in macaques is counter to gating and rebound in basal ganglia–thalamic communication

Task-related activity in the ventral thalamus, a major target of basal ganglia output, is often assumed to be permitted or triggered by changes in basal ganglia activity through gating- or rebound-like mechanisms. To test those hypotheses, we sampled single-unit activity from connected basal ganglia output and thalamic nuclei (globus pallidus-internus [GPi] and ventrolateral anterior nucleus [VLa]) in monkeys performing a reaching task. Rate increases were the most common peri-movement change in both nuclei. Moreover, peri-movement changes generally began earlier in VLa than in GPi. Simultaneously recorded GPi-VLa pairs rarely showed short-time-scale spike-to-spike correlations or slow across-trials covariations, and both were equally positive and negative. Finally, spontaneous GPi bursts and pauses were both followed by small, slow reductions in VLa rate. These results appear incompatible with standard gating and rebound models. Still, gating or rebound may be possible in other physiological situations: simulations show how GPi-VLa communication can scale with GPi synchrony and GPi-to-VLa convergence, illuminating how synchrony of basal ganglia output during motor learning or in pathological conditions may render this pathway effective. Thus, in the healthy state, basal ganglia-thalamic communication during learned movement is more subtle than expected, with changes in firing rates possibly being dominated by a common external source

Mutually exclusive STAT1 modifications identified by Ubc9/substrate dimerization-dependent SUMOylation

Post-translational modifications control the physiological activity of the signal transducer and activator of transcription STAT1. While phosphorylation at tyrosine Y701 is a prerequisite for STAT1 dimerization, its SUMOylation represses the transcriptional activity. Recently, we have demonstrated that SUMOylation at lysine K703 inhibits the phosphorylation of nearby localized Y701 of STAT1. Here, we analysed the influence of phosphorylation of Y701 on SUMOylation of K703 in vivo. For that reason, an Ubc9/substrate dimerization-dependent SUMOylation (USDDS) system was developed, which consists of fusions of the SUMOylation substrate and of the SUMO-conjugating enzyme Ubc9 to the chemically activatable heterodimerization domains FKBP and FRB, respectively. When FKBP fusion proteins of STAT1, p53, CRSP9, FOS, CSNK2B, HES1, TCF21 and MYF6 are coexpressed with Ubc9-FRB, treatment of HEK293 cells with the rapamycin-related dimerizer compound AP21967 induces SUMOylation of these proteins in vivo. For STAT1-FKBP and p53-FKBP we show that this SUMOylation takes place at their specific SUMOylation sites in vivo. Using USDDS, we then demonstrate that STAT1 phosphorylation at Y701 induced by interferon-β treatment inhibits SUMOylation of K703 in vivo. Thus, pY701 and SUMO-K703 of STAT1 represent mutually exclusive modifications, which prevent signal integration at this molecule and probably ensure the existence of differentially modified subpopulations of STAT1 necessary for its regulated nuclear cytoplasmic activation/inactivation cycle

Conservation of preparatory neural events in monkey motor cortex regardless of how movement is initiated

A time-consuming preparatory stage is hypothesized to precede voluntary movement. A putative neural substrate of motor preparation occurs when a delay separates instruction and execution cues. When readiness is sustained during the delay, sustained neural activity is observed in motor and premotor areas. Yet whether delay-period activity reflects an essential preparatory stage is controversial. In particular, it has remained ambiguous whether delay-period-like activity appears before non-delayed movements. To overcome that ambiguity, we leveraged a recently developed analysis method that parses population responses into putatively preparatory and movement-related components. We examined cortical responses when reaches were initiated after an imposed delay, at a self-chosen time, or reactively with low latency and no delay. Putatively preparatory events were conserved across all contexts. Our findings support the hypothesis that an appropriate preparatory state is consistently achieved before movement onset. However, our results reveal that this process can consume surprisingly little time

Thinking Television

Jacques Derrida _Echographies de la television. Entretiens filmes_ Paris: Editions Galilee / Institut national de l\'audiovisuel, 1996 ISBN: 2-7186-0480-8 187 pp