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

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

Functional ultrasound (fUS) using a 1-D-array transducer normally is insufficient to capture volumetric functional activity due to being restricted to imaging a single brain slice at a time. Typically, for volumetric fUS, functional recordings are repeated many times as the transducer is moved to a new location after each recording, resulting in a nonunique average mapping of the brain response and long scan times. Our objective was to perform volumetric 3-D fUS in an efficient and cost-effective manner. This was achieved 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. We show how the speed at which the 1-D-array is translated over the brain affects the sampling of the hemodynamic response (HR) during visual stimulation as well as the quality of the resulting power Doppler image (PDI). Functional activation maps were compared between stationary recordings, where only one functional slice is obtained for every recording, and our swept-3-D method, where volumetric fUS was achieved in a single functional recording. The results show that the activation maps obtained with our method closely resemble those obtained during a stationary recording for that same location, while our method is not restricted to functional imaging of a single slice. Lastly, a mouse brain subvolume of 6 mm is scanned at a volume rate of 1.5 s per volume, with a functional PDI reconstructed every 200\mu \text{m} , highlighting swept-3-D's potential for volumetric fUS. Our method provides an affordable alternative to volumetric fUS using 2-D-matrix transducers, with a high SNR due to using a fully sampled 1-D-array transducer, and without the need to repeat functional measurements for every 2-D slice, as is most often the case when using a 1-D-array. This places our swept-3-D method as a potentially valuable addition to conventional 2-D fUS, especially when investigating whole-brain functional connectivity, or when shorter recording durations are desired.</p

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

Functional ultrasound (fUS) using a 1-D-array transducer normally is insufficient to capture volumetric functional activity due to being restricted to imaging a single brain slice at a time. Typically, for volumetric fUS, functional recordings are repeated many times as the transducer is moved to a new location after each recording, resulting in a nonunique average mapping of the brain response and long scan times. Our objective was to perform volumetric 3-D fUS in an efficient and cost-effective manner. This was achieved 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. We show how the speed at which the 1-D-array is translated over the brain affects the sampling of the hemodynamic response (HR) during visual stimulation as well as the quality of the resulting power Doppler image (PDI). Functional activation maps were compared between stationary recordings, where only one functional slice is obtained for every recording, and our swept-3-D method, where volumetric fUS was achieved in a single functional recording. The results show that the activation maps obtained with our method closely resemble those obtained during a stationary recording for that same location, while our method is not restricted to functional imaging of a single slice. Lastly, a mouse brain subvolume of 6 mm is scanned at a volume rate of 1.5 s per volume, with a functional PDI reconstructed every 200\mu \text{m} , highlighting swept-3-D's potential for volumetric fUS. Our method provides an affordable alternative to volumetric fUS using 2-D-matrix transducers, with a high SNR due to using a fully sampled 1-D-array transducer, and without the need to repeat functional measurements for every 2-D slice, as is most often the case when using a 1-D-array. This places our swept-3-D method as a potentially valuable addition to conventional 2-D fUS, especially when investigating whole-brain functional connectivity, or when shorter recording durations are desired.</p

Neonatal development of the rat visual cortex: Synaptic function of GABAA receptor α subunits

Each GABAA receptor consists of two α and three other subunits. The spatial and temporal distribution of different α subunit isomeres expressed by the CNS is highly regulated. Here we study changes in functional contribution of different α subunits during neonatal development in rat visual cortex. First, we characterized postsynaptic α subunit expression in layer II-III neurons, using subunit-specific pharmacology combined with electrophysiological recordings in acutely prepared brain slices. This showed clear developmental downregulation of the effects of bretazenil (1 μm) and marked upregulation of the effect of 100 nM of zolpidem on the decay of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the concentrations used we interpret this as downregulation of the synaptic α3 and upregulation of α subunit. Furthermore, the effect of furosemide, being indicative of the functional contribution of α4, was increased between postnatal days 6 and 21. Our second aim was to study the effects of plasticity in α subunit expression on decay properties of GABAergic IPSCs. We found that bretazenil-sensitive IPSCs have the longest decay time constant in juvenile neurons. In mature neurons, zolpidem- and furosemide-sensitive IPSCs have relatively fast decay kinetics, whereas bretazenil-sensitive IPSCs decay relatively slowly. Analysis of α1 deficient mice and α1 antisense oligonucleotide deletion in rat explants showed similar results to those obtained by zolpidem application. Thus, distinct α subunit contributions create heterogeneity in developmental acceleration of IPSC decay in neocortex

Mice lacking the major adult GABAA receptor subtype have normal number of synapses, but retain juvenile IPSC kinetics until adulthood

There is a large variation in structurally and functionally different GABAA receptor subtypes. The expression pattern of GABAA receptor subunits is highly regulated, both temporarily and spatially. Especially during development, profound changes in subunit expression have been described. In most brain areas, the GABAA receptor α1 subunit replaces the α2 and/or α3 subunit as major α1 subunit. This is accompanied by a marked decrease in the open time of GABAA receptors and hence in the duration of postsynaptic responses. We describe here the development of GABAergic, synaptic transmission in mice lacking the α1 subunit. We show that α1 is to a large extent-but not entirely-responsible for the relatively short duration of postsynaptic responses in the developing and the mature brain. However, α1 already affects GABAergic transmission in the neonatal cerebral cortex when it is only sparsely expressed. It appears that the α1 -/- mice do not show a large reduction in GABAergic synapses but do retain long-lasting postsynaptic currents into adulthood. Hence, they form a good model to study the functional role of developmental GABAA receptor subunit switching

A Systematic Review of Direct Outputs from the Cerebellum to the Brainstem and Diencephalon in Mammals

The cerebellum is involved in many motor, autonomic and cognitive functions, and new tasks that have a cerebellar contribution are discovered on a regular basis. Simultaneously, our insight into the functional compartmentalization of the cerebellum has markedly improved. Additionally, studies on cerebellar output pathways have seen a renaissance due to the development of viral tracing techniques. To create an overview of the current state of our understanding of cerebellar efferents, we undertook a systematic review of all studies on monosynaptic projections from the cerebellum to the brainstem and the diencephalon in mammals. This revealed that important projections from the cerebellum, to the motor nuclei, cerebral cortex, and basal ganglia, are predominantly di- or polysynaptic, rather than monosynaptic. Strikingly, most target areas receive cerebellar input from all three cerebellar nuclei, showing a convergence of cerebellar information at the output level. Overall, there appeared to be a large level of agreement between studies on different species as well as on the use of different types of neural tracers, making the emerging picture of the cerebellar output areas a solid one. Finally, we discuss how this cerebellar output network is affected by a range of diseases and syndromes, with also non-cerebellar diseases having impact on cerebellar output areas

Purkinje cells translate subjective salience into readiness to act and choice performance

The brain selectively allocates attention from a continuous stream of sensory input. This process is typically attributed to computations in distinct regions of the forebrain and midbrain. Here, we explore whether cerebellar Purkinje cells encode information about the selection of sensory inputs and could thereby contribute to non-motor forms of learning. We show that complex spikes of individual Purkinje cells change the sensory modality they encode to reflect changes in the perceived salience of sensory input. Comparisons with mouse models deficient in cerebellar plasticity suggest that changes in complex spike activity instruct potentiation of Purkinje cells simple spike firing, which is required for efficient learning. Our findings suggest that during learning, climbing fibers do not directly guide motor output, but rather contribute to a general readiness to act via changes in simple spike activity, thereby bridging the sequence from non-motor to motor functions

WhiskEras 2.0:Fast and Accurate Whisker Tracking in Rodents

Mice and rats can rapidly move their whiskers when exploring the environment. Accurate description of these movements is important for behavioral studies in neuroscience. Whisker tracking is, however, a notoriously difficult task due to the fast movements and frequent crossings and juxtapositionings among whiskers. We have recently developed WhiskEras, a computer-vision-based algorithm for whisker tracking in untrimmed, head-restrained mice. Although WhiskEras excels in tracking the movements of individual unmarked whiskers over time based on high-speed videos, the initial version of WhiskEras still had two issues preventing its widespread use: it involved tuning a great number of parameters manually to adjust for different experimental setups, and it was slow, processing less than 1 frame per second. To overcome these problems, we present here WhiskEras 2.0, in which the unwieldy stages of the initial algorithm were improved. The enhanced algorithm is more robust, not requiring intense parameter tuning. Furthermore, it was accelerated by first porting the code from MATLAB to C++ and then using advanced parallelization techniques with CUDA and OpenMP to achieve a speedup of at least 75x when processing a challenging whisker video. The improved WhiskEras 2.0 is made publicly available and is ready for processing high-speed videos, thus propelling behavioral research in neuroscience, in particular on sensorimotor integration.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Quantum & Computer EngineeringComputer Engineerin

Requirement of TrkB for synapse elimination in developing cerebellar Purkinje cells

The receptor tyrosine kinase TrkB and its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5), are critically important for growth, survival and activity-dependent synaptic strengthening in the central nervous system. These TrkB-mediated actions occur in a highly cell-type specific manner. Here we report that cerebellar Purkinje cells, which are richly endowed with TrkB receptors, develop a normal morphology in trkB-deficient mice. Thus, in contrast to other types of neurons, Purkinje cells do not need TrkB for dendritic growth and spine formation. Instead, we find a moderate delay in the maturation of GABAergic synapses and, more importantly, an abnormal multiple climbing fiber innervation in Purkinje cells in trkB-deficient mice. Thus, our results demonstrate an involvement of TrkB receptors in synapse elimination and reveal a new role for receptor tyrosine kinases in the brain

The integrated brain network that controls respiration

Respiration is a brain function on which our lives essentially depend. Control of respiration ensures that the frequency and depth of breathing adapt continuously to metabolic needs. In addition, the respiratory control network of the brain has to organize muscular synergies that integrate ventilation with posture and body movement. Finally, respiration is coupled to cardiovascular function and emotion. Here, we argue that the brain can handle this all by integrating a brainstem central pattern generator circuit in a larger network that also comprises the cerebellum. Although currently not generally recognized as a respiratory control center, the cerebellum is well known for its coordinating and modulating role in motor behavior, as well as for its role in the autonomic nervous system. In this review, we discuss the role of brain regions involved in the control of respiration, and their anatomical and functional interactions. We discuss how sensory feedback can result in adaptation of respiration, and how these mechanisms can be compromised by various neurological and psychological disorders. Finally, we demonstrate how the respiratory pattern generators are part of a larger and integrated network of respiratory brain regions