Repository for Publications and Research Data
News from the ETH Library
Recently Added
How Local Excitation-Inhibition Ratio Impacts the Whole Brain Dynamics
Item type: Journal Article
Deco, Gustavo; Ponce-Alvarez, Adrián; Hagmann, Patric; et al. (2014)
The spontaneous activity of the brain shows different features at different scales. On one hand, neuroimaging studies show that long-range correlations are highly structured in spatiotemporal patterns, known as resting-state networks, on the other hand, neurophysiological reports show that short-range correlations between neighboring neurons are low, despite a large amount of shared presynaptic inputs. Different dynamical mechanisms of local decorrelation have been proposed, among which is feedback inhibition. Here, we investigated the effect of locally regulating the feedback inhibition on the global dynamics of a large-scale brain model, in which the long-range connections are given by diffusion imaging data of human subjects. We used simulations and analytical methods to show that locally constraining the feedback inhibition to compensate for the excess of long-range excitatory connectivity, to preserve the asynchronous state, crucially changes the characteristics of the emergent resting and evoked activity. First, it significantly improves the model's prediction of the empirical human functional connectivity. Second, relaxing this constraint leads to an unrealistic network evoked activity, with systematic coactivation of cortical areas which are components of the default-mode network, whereas regulation of feedback inhibition prevents this. Finally, information theoretic analysis shows that regulation of the local feedback inhibition increases both the entropy and the Fisher information of the network evoked responses. Hence, it enhances the information capacity and the discrimination accuracy of the global network. In conclusion, the local excitation-inhibition ratio impacts the structure of the spontaneous activity and the information transmission at the large-scale brain level. © 2014 the authors.
Neutralization of Nogo-A Enhances Synaptic Plasticity in the Rodent Motor Cortex and Improves Motor Learning in Vivo
Item type: Journal Article
Zemmar, Ajmal; Weinmann, Oliver; Kellner, Yves; et al. (2014)
The membrane protein Nogo-A is known as an inhibitor of axonal outgrowth and regeneration in the CNS. However, its physiological functions in the normal adult CNS remain incompletely understood. Here, we investigated the role of Nogo-A in cortical synaptic plasticity and motor learning in the uninjured adult rodent motor cortex. Nogo-A and its receptor NgR1 are present at cortical synapses. Acute treatment of slices with function-blocking antibodies (Abs) against Nogo-A or against NgR1 increased long-term potentiation (LTP) induced by stimulation of layer 2/3 horizontal fibers. Furthermore, anti-Nogo-A Ab treatment increased LTP saturation levels, whereas long-term depression remained unchanged, thus leading to an enlarged synaptic modification range. In vivo, intrathecal application of Nogo-A-blocking Abs resulted in a higher dendritic spine density at cortical pyramidal neurons due to an increase in spine formation as revealed by in vivo two-photon microscopy. To investigate whether these changes in synaptic plasticity correlate with motor learning, we trained rats to learn a skilled forelimb-reaching task while receiving anti-Nogo-A Abs. Learning of this cortically controlled precision movement was improved upon anti-Nogo-A Ab treatment. Our results identify Nogo-A as an influential molecular modulator of synaptic plasticity and as a regulator for learning of skilled movements in the motor cortex. © 2014 the authors.
Event-History Analysis for Psychological Time-to-Event Data: A Tutorial in R With Examples in Bayesian and Frequentist Workflows
Item type: Journal Article
Panis, Sven; Ramsey, Richard (2026)
Time-to-event data, such as response times and saccade latencies, form a cornerstone of experimental psychology and have had a widespread impact on the understanding of human cognition. However, the orthodox method for analyzing such data-comparing means between conditions-is known to conceal valuable information about the timeline of psychological effects, such as their onset time and how they evolve over time. The ability to reveal finer-grained "temporal states" of cognitive processes can have important consequences for theory development by qualitatively changing the key inferences that are drawn from psychological data. Well-established analytical approaches, such as event-history analysis (EHA), can evaluate the detailed shape of time-to-event distributions and thus characterize the time course of psychological states. One barrier to wider use of EHA, however, is that the analytical workflow is typically more time-consuming and complex than orthodox approaches. To help achieve broader uptake of EHA, in this article, we outline a set of tutorials that detail one distributional method, known as discrete-time EHA. We touch on several key aspects of the workflow, such as how to process raw data and specify regression models, and we also consider the implications for experimental design. We finish the article by considering the benefits of the approach for understanding psychological states and its limitations. Finally, the project is written in R and freely available, which means the approach can easily be adapted to other data sets.
Differential GABAergic and Glycinergic Inputs of Inhibitory Interneurons and Purkinje Cells to Principal Cells of the Cerebellar Nuclei
Item type: Journal Article
Husson, Zoe; Rousseau, Charly V.; Broll, Ilja; et al. (2014)
The principal neurons of the cerebellar nuclei (CN), the sole output of the olivo-cerebellar system, receive a massive inhibitory input from Purkinje cells (PCs) of the cerebellar cortex. Morphological evidence suggests that CN principal cells are also contacted by inhibitory interneurons, but the properties of this connection are unknown. Using transgenic, tracing, and immunohistochemical approaches in mice, we show that CNinterneurons form a large heterogeneous population with GABA/glycinergic phenotypes, distinct from GABAergic olive-projecting neurons.CNinterneurons are found to contact principal output neurons, via glycine receptor (GlyR)-enriched synapses, virtually devoid of the mainGABAreceptor (GABAR) subunitsα1 and γ2. Those clusters account for 5% of the total number of inhibitory receptor clusters on principal neurons. Brief optogenetic stimulations of CN interneurons, through selective expression of channelrhodopsin 2 after viral-mediated transfection of the flexed gene in GlyT2-Cre transgenic mice, evoked fast IPSCs in principal cells. GlyR activation accounted for 15% of interneuron IPSC amplitude, while the remaining current was mediated by activation of GABAR. Surprisingly, small GlyR clusters were also found at PC synapses onto principal CN neurons in addition to α1 and γ2 GABAR subunits. However, GlyR activation was found to account for <3% of the PC inhibitory synaptic currents evoked by electrical stimulation. This work establishes CN glycinergic neurons as a significant source of inhibition to CN principal cells, forming contacts molecularly distinct from, but functionally similar to, Purkinje cell synapses. Their impact on CN output, motor learning, and motor execution deserves further investigation. © 2014 the authors.
Dopaminergic Role in Regulating Neurophysiological Markers of Sleep Homeostasis in Humans
Item type: Journal Article
Holst, Sebastian C.; Bersagliere, Alessia; Bachmann, Valerie; et al. (2014)
While dopamine affects fundamental brain processes such as movement control, emotional responses, addiction, and pain, the roles for this neurotransmitter in regulating wakefulness and sleep are incompletely understood. Genetically modified animal models with reduced dopamine clearance exhibit hypersensitivity to caffeine, reduced-responsiveness to modafinil, and increased homeostatic response to prolonged wakefulness when compared with wild-type animals. Here we studied sleep–wake regulation in humans and combined pharmacogenetic and neurophysiologic methods to analyze the effects of the 3′-UTR variable-number-tandem-repeat polymorphism of the gene (DAT1, SLC6A3) encoding dopamine transporter (DAT). Previous research demonstrated that healthy homozygous 10-repeat (10R/10R) allele carriers of this genetic variant have reduced striatal DAT protein expression when compared with 9-repeat (9R) allele carriers. Objective and subjective estimates of caffeine sensitivity were higher in 10R allele homozygotes than in carriers of the 9R allele. Moreover, caffeine and modafinil affected wakefulness-induced changes in functional bands (delta, sigma, beta) of rhythmic brain activity in wakefulness and sleep in a DAT1 genotype-dependent manner. Finally, the sleep deprivation-induced increase in well established neurophysiologic markers of sleep homeostasis, including slow-wave sleep, electroencephalographic slow-wave activity (0.5–4.5 Hz), and number of low-frequency (0.5–2.0 Hz) oscillations in non-rapid-eye-movement sleep, was significantly larger in the 10R/10R genotype than in the 9R allele carriers of DAT1. Together, the data suggest that the dopamine transporter contributes to homeostatic sleep–wake regulation in humans.