Cerebellar and Extracerebellar Involvement in Mouse Eyeblink Conditioning: the ACDC Model

Over the past decade the advent of mouse transgenics has generated new perspectives on the study of cerebellar molecular mechanisms that are essential for eyeblink conditioning. However, it also appears that results from eyeblink conditioning experiments done in mice differ in some aspects from results previously obtained in other mammals. In this review article we will, based on studies using (cell-specific) mouse mutants and region-specific lesions, re-examine the general eyeblink behavior in mice and the neuro-anatomical circuits that might contribute to the different peaks in the conditioned eyeblink trace. We conclude that the learning process in mice has at least two stages: An early stage, which includes short-latency responses that are at least partly controlled by extracerebellar structures such as the amygdala, and a later stage, which is represented by well-timed conditioned responses that are mainly controlled by the pontocerebellar and olivocerebellar systems. We refer to this overall concept as the Amygdala-Cerebellum-Dynamic-Conditioning Model (ACDC model)

High frequency burst firing of granule cells ensures transmission at the parallel fiber to purkinje cell synapse at the cost of temporal coding.

Cerebellar granule cells (GrCs) convey information from mossy fibers (MFs) to Purkinje cells (PCs) via their parallel fibers (PFs). MF to GrC signaling allows transmission of frequencies up to 1 kHz and GrCs themselves can also fire bursts of action potentials with instantaneous frequencies up to 1 kHz. So far, in the scientific literature no evidence has been shown that these high-frequency bursts also exist in awake, behaving animals. More so, it remains to be shown whether such high-frequency bursts can transmit temporally coded information from MFs to PCs and/or whether these patterns of activity contribute to the spatiotemporal filtering properties of the GrC layer. Here, we show that, upon sensory stimulation in both un-anesthetized rabbits and mice, GrCs can show bursts that consist of tens of spikes at instantaneous frequencies over 800 Hz. In vitro recordings from individual GrC-PC pairs following high-frequency stimulation revealed an overall low initial release probability of ~0.17. Nevertheless, high-frequency burst activity induced a short-lived facilitation to ensure signaling within the first few spikes, which was rapidly followed by a reduction in transmitter release. The facilitation rate among individual GrC-PC pairs was heterogeneously distributed and could be classified as either "reluctant" or "responsive" according to their release characteristics. Despite the variety of efficacy at individual connections, grouped activity in GrCs resulted in a linear relationship between PC response and PF burst duration at frequencies up to 300 Hz allowing rate coding to persist at the network level. Together, these findings support the hypothesis that the cerebellar granular layer acts as a spatiotemporal filter between MF input and PC output (D'Angelo and De Zeeuw, 2009)

A potential role for the cerebellar nuclei in absence seizures

© 2013 Alva et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Poster presented ar CNS 2013Non peer reviewe

Music Affects Rodents: A Systematic Review of Experimental Research

Background: There is rapidly emerging interest in music interventions in healthcare. Music interventions are widely applicable, inexpensive, without side effects, and easy to use. It is not precisely known how they exert positive effects on health outcomes. Experimental studies in animal models might reveal more about the pathophysiological mechanisms of music interventions.Methods: We performed a systematic review of experimental research in rodents. The electronic databases EMBASE, Medline(ovidSP), Web-Of-Science, PsycINFO, Cinahl, PubMed publisher, Cochrane, and Google scholar were searched for publications between January 1st 1960 and April 22nd 2017. Eligible were English–written, full-text publications on experimental research in rodents comparing music vs. a control situation. Outcomes were categorized in four domains: brain structure and neuro-chemistry; behavior; immunology; and physiology. Additionally, an overview was generated representing the effects of various types of music on outcomes. Bias in studies was assessed with the SYRCLE Risk of Bias tool. A meta-analysis was not feasible due to heterogeneous outcomes and lack of original outcome data.Results: Forty-two studies were included. Music-exposed rodents showed statistically significant increases in neuro-chemistry, such as higher BDNF levels, as well as an enhanced propensity for neurogenesis and neuroplasticity. Furthermore, music exposure was linked with statistically significantly improved spatial and auditory learning, reduced anxiety-related behavior, and increased immune responses. Various statistically significant changes occurred in physiological parameters such as blood pressure and (para)sympathetic nerve activity following music interventions. The majority of studies investigated classical music interventions, but other types of music exerted positive effects on outcomes as well. The SYRCLE risk of bias assessment revealed unclear risk of bias in all studies.Conclusions: Music interventions seem to improve brain structure and neuro-chemistry; behavior; immunology; and physiology in rodents. Further research is necessary to explore and optimize the effect of music interventions, and to evaluate its effects in humans

Synchronicity and rhythmicity of purkinje cell firing during generalized spike-and-wave discharges in a natural mouse model of absence epilepsy

Absence epilepsy is characterized by the occurrence of generalized spike and wave discharges (GSWDs) in electrocorticographical (ECoG) recordings representing oscillatory activity in thalamocortical networks. The oscillatory nature of GSWDs has been shown to be reflected in the simple spike activity of cerebellar Purkinje cells and in the activity of their target neurons in the cerebellar nuclei, but it is unclear to what extent complex spike activity is implicated in generalized epilepsy. Purkinje cell complex spike firing is elicited by climbing fiber activation and reflects action potential firing in the inferior olive. Here, we investigated to what extent modulation of complex spike firing is reflected in the temporal patterns of seizures. Extracellular single-unit recordings in awake, headrestrained homozygous tottering mice, which suffer from a mutation in the voltage-gated CaV2.1 calcium channel, revealed that a substantial proportion of Purkinje cells (26%) showed increased complex spike activity and rhythmicity during GSWDs. Moreover, Purkinje cells, recorded either electrophysiologically or by using Ca2+-imaging, showed a significant increase in complex spike synchronicity for both adjacent and remote Purkinje cells during ictal events. These seizure-related changes in firing frequency, rhythmicity and synchronicity were most prominent in the lateral cerebellum, a region known to receive cerebral input via the inferior olive. These data indicate profound and widespread changes in olivary firing that are most likely induced by seizure-related activity changes in the thalamocortical network, thereby highlighting the possibility that olivary neurons can compensate for pathological brain-state changes by dampening oscillations

Swept-3-D Ultrasound Imaging of the Mouse Brain Using a Continuously Moving 1-D-Array-Part I:Doppler Imaging

Volumetric 3-D Doppler ultrasound imaging can be used to investigate large scale blood dynamics outside of the limited view that conventional 2-D power Doppler images (PDIs) provide. To create 3-D PDIs, 2-D-matrix array transducers can be used to insonify a large volume for every transmission; however, these matrices suffer from low sensitivity, high complexity, and high cost. More typically, a 1-D-Array transducer is used to scan a series of stationary 2-D PDIs, after which a 3-D volume is created by concatenating the 2-D PDIs in postprocessing, which results in long scan times due to repeated measurements. Our objective was to achieve volumetric 3-D Doppler ultrasound imaging with a high Doppler sensitivity, similar to that of a typical stationary recording using a 1-D-Array transducer, while being more affordable than using 2-D-matrix arrays. We achieved this by mounting a 1-D-Array transducer to a high-precision motorized linear stage and continuously translating over the mouse brain in a sweeping manner. For Part I of this article, we focused on creating the best vascular images by investigating how to best combine filtered beamformed ultrasound frames, which were not acquired at the same spatial locations, into PDIs. Part II focuses on the implications of sampling transient brain hemodynamics through functional ultrasound (fUS) while continuously translating over the mouse brain. In Part I, we show how the speed at which we sweep our 1-D-Array transducer affects the Doppler spectrum in a flow phantom. In vivo recordings were performed on the mouse brain while varying the sweeping speed, showing how higher sweeping speeds negatively affect the PDI quality. A weighting vector is found to combine frames while continuously moving over the mouse brain, allowing us to create swept PDIs of similar sensitivity when compared with those obtained using a stationary 1-D-Array while allowing a significantly higher 3-D Doppler volume rate and maintaining the benefits of having a low computational and monetary cost. We show that a vascular subvolume of 6 mm can be scanned in 2.5 s, with a PDI reconstructed every $200 \mu \text{m}$ , outperforming classical staged recording methods.</p

Regular Patterns in Cerebellar Purkinje Cell Simple Spike Trains

Background. Cerebellar Purkinje cells (PC) in vivo are commonly reported to generate irregular spike trains, documented by high coefficients of variation of interspike-intervals (ISI). In strong co

BrainFrame: A node-level heterogeneous accelerator platform for neuron simulations

Objective: The advent of High-Performance Computing (HPC) in recent years has led to its increasing use in brain study through computational models. The scale and complexity of such models are constantly increasing, leading to challenging computational requirements. Even though modern HPC platforms can often deal with such challenges, the vast diversity of the modeling field does not permit for a single acceleration (or homogeneous) platform to effectively address the complete array of modeling requirements. Approach: In this paper we propose and build BrainFrame, a heterogeneous acceleration platform, incorporating three distinct acceleration technologies, a Dataflow Engine, a Xeon Phi and a GP-GPU. The PyNN framework is also integrated into the platform. As a challenging proof of concept, we analyze the performance of BrainFrame on different instances of a state-of-the-art neuron model, modeling the Inferior- Olivary Nucleus using a biophysically-meaningful, extended Hodgkin-Huxley representation. The model instances take into account not only the neuronal- network dimensions but also different network-connectivity circumstances that can drastically change application workload characteristics. Main results: The synthetic approach of three HPC technologies demonstrated that BrainFrame is better able to cope with the modeling diversity encountered. Our performance analysis shows clearly that the model directly affect performance and all three technologies are required to cope with all the model use cases.Comment: 16 pages, 18 figures, 5 table

Anatomical Pathways Involved in Generating and Sensing Rhythmic Whisker Movements

The rodent whisker system is widely used as a model system for investigating sensorimotor integration, neural mechanisms of complex cognitive tasks, neural development, and robotics. The whisker pathways to the barrel cortex have received considerable attention. However, many subcortical structures are paramount to the whisker system. They contribute to important processes, like filtering out salient features, integration with other senses, and adaptation of the whisker system to the general behavioral state of the animal. We present here an overview of the brain regions and their connections involved in the whisker system. We do not only describe the anatomy and functional roles of the cerebral cortex, but also those of subcortical structures like the striatum, superior colliculus, cerebellum, pontomedullary reticular formation, zona incerta, and anterior pretectal nucleus as well as those of level setting systems like the cholinergic, histaminergic, serotonergic, and noradrenergic pathways. We conclude by discussing how these brain regions may affect each other and how they together may control the precise timing of whisker movements and coordinate whisker perception