Chris I De Zeeuw

Erasmus University Rotterdam | EUR · Erasmus Medical Center (MC)

Many children suffer from neurodevelopmental aberrations that have long-term effects. To understand the consequences of pathological processes during particular periods in neurodevelopment, one has to understand the differences in the developmental timelines of brain regions. The cerebellum is one of the first brain structures to differentiate duri...

Many children suffer from neurodevelopmental aberrations that have long-term effects. To un-derstand the consequences of pathological processes during particular periods in neurodevelop-ment, one has to understand the differences in the developmental timelines of brain regions. The cerebellum is one of the first brain structures to differentiate du...

Physical exercise has repeatedly been reported to have advantageous effects on brain functions, including learning and memory formation. However, objective tools to measure such effects are often lacking. Eyeblink conditioning is a well-characterised method for studying the neural basis of associative learning. As such, this paradigm has potential...

BACKGROUND To this day, the mainstay of human neuroimaging remains (functional) Magnetic Resonance Imaging (fMRI), where subjects are asked to lie completely still and silent in a noisy scanner. Many key questions in clinical care and neuroscience remain poorly studied because of fMRI’s inability to facilitate natural behavior such as locomotion or...

The molecular and cellular organization of the primate cerebellum remains poorly characterized. We obtained single-cell spatial transcriptomic atlases of macaque, marmoset, and mouse cerebella and identified primate-specific cell subtypes, including Purkinje cells and molecular-layer interneurons, that show different expression of the glutamate ion...

The cerebellum is critical for coordinating movements related to eating, drinking and swallowing. Cerebellar Purkinje cell activity has been shown to encode ongoing tongue movements, but it is unclear how this activity can alter the trajectory of the tongue. To elucidate the impact of Purkinje cells on goal-directed tongue movements, we recorded th...

Visuomotor association involves linking an arbitrary visual cue to a well-learned movement. Transient inactivation of Crus I/II impairs primates’ ability to learn new associations and delays motor responses without affecting the kinematics of the movement. The simple spikes of Purkinje cells in the Crus regions signal cognitive errors as monkeys le...

The role of cerebellum in controlling eye movements is well established, but its contribution to more complex forms of visual behavior has remained elusive. To study cerebellar activity during visual attention we recorded extracellular activity of dentate nucleus (DN) neurons in two non-human primates (NHPs). NHPs were trained to read the direction...

The role of cerebellum in controlling eye movements is well established, but its contribution to more complex forms of visual behavior has remained elusive. To study cerebellar activity during visual attention we recorded extracellular activity of dentate nucleus (DN) neurons in two non-human primates (NHPs). NHPs were trained to read the direction...

The delicate balance between discrimination and generalization of responses is crucial for survival in our ever-changing environment. In particular, it is important to understand how stimulus discrimination affects the level of stimulus generalization. For example, when we use non-differential training for Pavlovian eyeblink conditioning to investi...

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The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also non-motor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target...

The role of cerebellum in controlling eye movements is well established, but its contribution to more complex forms of visual behavior has remained elusive. To study cerebellar activity during visual attention we recorded extracellular activity of dentate nucleus (DN) neurons in two non-human primates (NHPs). NHPs were trained to read the direction...

The investigation of the dynamics of Purkinje cell (PC) activity is crucial to unravel the role of the cerebellum in motor control, learning and cognitive processes. Within the cerebellar cortex (CC), these neurons receive all the incoming sensory and motor information, transform it and generate the entire cerebellar output. The relatively homogeno...

Despite its uniform appearance, the cerebellar cortex is highly heterogeneous in terms of structure, genetics and physiology. Purkinje cells (PCs), the principal and sole output neurons of the cerebellar cortex, can be categorized into multiple populations that differentially express molecular markers and display distinctive physiological features....

According to the motor learning theory by Albus and Ito, synaptic depression at the parallel fibre to Purkinje cells synapse (pf-PC) is the main substrate responsible for learning sensorimotor contingencies under climbing fibre control. However, recent experimental evidence challenges this relatively monopolistic view of cerebellar learning. Bidire...

Neuroscience heavily relies on animal welfare in laboratory rodents as it can significantly affect brain development, cognitive function and memory formation. Unfortunately, laboratory animals are often raised in artificial environments devoid of physical and social stimuli, potentially leading to biased outcomes in behavioural assays. To assess th...

Unhealthy ageing poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the ageing process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, promoting healthy longevity in the old population. In response to the challenge of the ageing population and with a...

Gait ataxia is one of the most common and impactful consequences of cerebellar dysfunction. Purkinje cells, the sole output neurons of the cerebellar cortex, are often involved in the underlying pathology, but their specific functions during locomotor control in health and disease remain obfuscated. We aimed to describe the effect of gradual adult-...

A significant percentage of children suffer from neurodevelopmental aberrations, which have long-term effects on both individuals and society. Since the developmental timelines of different brain regions vary, the type, severity and timing of harmful exposures are crucial for understanding the specific pathological processes and consequences involv...

Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system....

The olivocerebellar system, which is critical for sensorimotor performance and learning, functions through modules with feedback loops. The main feedback to the inferior olive comes from the cerebellar nuclei (CN), which are predominantly GABAergic and contralateral. However, for the subnucleus d of the caudomedial accessory olive (cdMAO), a crucia...

Four-dimensional ultrasound imaging of complex biological systems such as the brain is technically challenging because of the spatiotemporal sampling requirements. We present computational ultrasound imaging (cUSi), an imaging method that uses complex ultrasound fields that can be generated with simple hardware and a physical wave prediction model...

Tests of human brain circuit function typically require fixed equipment in lab environments. We have developed a smartphone-based platform for neurometric testing. This platform, which uses AI models like computer vision, is optimized for at-home use and produces reproducible, robust results on a battery of tests, including eyeblink conditioning, p...

Recently, a Y727C variant in the dual-specific 3′,5′-cyclic nucleotide phosphodiesterase 11A (PDE11A-Y727C) was linked to increased sleep quality and reduced myopia risk in humans. Given the well-established role that the PDE11 substrates cAMP and cGMP play in eye physiology and sleep, we determined if (1) PDE11A protein is expressed in the retina...

Precise temporal control of sensorimotor coordination and adaptation is a fundamental basis of animal behavior. How different brain regions are involved in regulating the flexible temporal adaptation remains elusive. Here we investigated the neuronal dynamics of cerebellar interposed nucleus (IpN) and medial prefrontal cortex (mPFC) neurons during...

Local feedforward and recurrent connectivity are rife in the frontal areas of the cerebral cortex, which gives rise to rich heterogeneous dynamics observed in such areas. Recently, similar local connectivity motifs have been discovered among Purkinje and molecular layer interneurons of the cerebellar cortex, however, task-related activity in these...

The whisker system is widely used as a model system for understanding sensorimotor integration. Purkinje cells in the crus regions of the cerebellum have been reported to linearly encode whisker midpoint, but it is unknown whether the paramedian and simplex lobules as well as their target neurons in the cerebellar nuclei also encode whisker kinemat...

Associative learning during delay eyeblink conditioning (EBC) depends on an intact cerebellum. However, the relative contribution of changes in the cerebellar nuclei to learning remains a subject of ongoing debate. In particular, little is known about the changes in synaptic inputs to cerebellar nuclei neurons that take place during EBC and how the...

Recently, a Y727C variant in the dual-specific 3,5-cyclic nucleotide phosphodiesterase 11A (PDE11A-Y727C) was linked to increased sleep quality and reduced myopia risk in humans. Given the well-established role that the PDE11 substrates cAMP and cGMP play in eye physiology and sleep, we determined if 1) PDE11A protein is expressed in the retina or...

Functional ultrasound (fUS) using a 1D-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 n...

Social deficits play a role in numerous psychiatric, neurological and neurodevelopmental disorders. Relating complex behavior, such as social interaction, to brain activity remains one of the biggest goals and challenges in neuroscience. Availability of standardized behavioral tests that assess social preference is however, limited. Here, we presen...

The cerebellum is important for motor performance and adaptation as well as cognition. Sleep is essential for optimizing of all these functions, but it remains to be elucidated how sleep affects cerebellar processing. It has been suggested that sleep periods with muscle twitches entrain the cerebellum with a copy of motor commands and subsequent se...

Williams syndrome is a developmental disorder caused by a microdeletion entailing loss of a single copy of 25-27 genes on chromosome 7q11.23. Patients with Williams syndrome suffer from cardiovascular and neuropsychological symptoms. So far, the structural abnormalities of the cardiovascular system in Williams syndrome have been attributed to the l...

A significant percentage of children suffer from neurodevelopmental aberrations, which have long-term effects on both individuals and society. Since the developmental timelines of different brain regions vary, the type, severity and timing of harmful exposures are crucial for understanding the specific pathological processes and consequences involv...

In Nyxnob mice, a model for congenital nystagmus associated with congenital stationary night blindness (CSNB), synchronous oscillating retinal ganglion cells (RGCs) lead to oscillatory eye movements, i.e. nystagmus. Given the specific expression of mGluR6 and Cav1.4 in the photoreceptor to bipolar cell synapses, as well as their clinical associatio...

Volumetric 3D Doppler ultrasound imaging can be used to investigate large scale blood dynamics outside of the limited view that conventional 2D power Doppler images (PDIs) provide. To create 3D PDIs, 2D-matrix array transducers can be used to insonify a large volume for every transmission, however these matrices suffer from low sensitivity, high co...

Neuroscience heavily relies on animal welfare in laboratory rodents as it can significantly affect brain development, cognitive function, and memory formation. Unfortunately, laboratory animals are often raised in artificial environments devoid of physical and social stimuli, potentially leading to biased outcomes in behavioural assays. To assess t...

BACKGROUND Neurosurgical resection of brain tumors resembles a balancing act between maximing extent of tumor resection (efficacy) and minimizing the risk of post-operative neurological deficits (safety). Given the difficulty of this trade-off, it is surprising how limited the neurosurgeon’s intra-operative tools are. To this day, neurosurgeons sti...

Background Gait ataxia is one of the most common and impactful consequences of cerebellar dysfunction. Purkinje cells, the sole output neurons of the cerebellar cortex, are often involved in the underlying pathology, but their specific functions during locomotor control in health and disease remain obfuscated. Objectives We aimed to describe the ef...

Associative learning during delay eyeblink conditioning (EBC) depends on an intact cerebellum. However, the relative contribution of changes in the cerebellar nuclei to learning remains a subject of ongoing debate. In particular, little is known about the changes in synaptic inputs to cerebellar nuclei neurons that take place during EBC and how the...

Cerebellar output neurons integrate strong inhibitory input and weaker excitatory input during the control of spontaneous and learned movements. A new study sheds light on how those inputs are integrated during associative swimming in zebrafish larvae.

The inferior olive provides the climbing fibers to Purkinje cells in the cerebellar cortex, where they elicit all-or-none complex spikes and control major forms of plasticity. Given their important role in both short-term and long-term coordination of cerebellum-dependent behaviors, it is paramount to understand the factors that determine the outpu...

The inferior olive provides the climbing fibers to Purkinje cells in the cerebellar cortex, where they elicit all-or-none complex spikes and control major forms of plasticity. Given their important role in both short-term and long-term coordination of cerebellum-dependent behaviors, it is paramount to understand the factors that determine the outpu...

The inferior olive provides the climbing fibers to Purkinje cells in the cerebellar cortex, where they elicit all-or-none complex spikes and control major forms of plasticity. Given their important role in both short-term and long-term coordination of cerebellum-dependent behaviors, it is paramount to understand the factors that determine the outpu...

The inferior olive provides the climbing fibers to Purkinje cells in the cerebellar cortex, where they elicit all-or-none complex spikes and control major forms of plasticity. Given their important role in both short-term and long-term coordination of cerebellum-dependent behaviors, it is paramount to understand the factors that determine the outpu...

The classification of neuronal subpopulations has significantly advanced, yet its relevance for behavior remains unclear. The highly organized flocculus of the cerebellum, known to fine-tune multi-axial eye movements, is an ideal substrate for the study of potential functions of neuronal subpopulations. Here, we demonstrate that its recently identi...

According to Marr’s motor learning theory, plasticity at the parallel fibre to Purkinje cells synapse (pf-PC) is the main substrate responsible for learning sensorimotor contingencies under climbing fibre control. However, the discovery of multiple forms of plasticity distributed over different cerebellar circuit synapses prompts to remap the cereb...

Neural activity exhibits oscillations, bursts, and resonance, enhancing responsiveness at preferential frequencies. For example, theta-frequency bursting and resonance in granule cells facilitate synaptic transmission and plasticity mechanisms at the input stage of the cerebellar cortex. However, whether theta-frequency bursting of Purkinje cells i...

Surgical resection of spinal cord hemangioblastomas remains a challenging endeavor: the neurosurgeon’s aim to reach total tumor resections directly endangers their aim to minimize post-operative neurological deficits. The currently available tools to guide the neurosurgeon’s intra-operative decision-making consist mostly of pre-operative imaging te...

In Nyxnob mice, a model for congenital nystagmus associated with congenital stationary night blindness (CSNB), synchronous oscillating retinal ganglion cells (RGCs) lead to oscillatory eye movements, i.e., nystagmus. Given the distribution of mGluR6 and Cav1.4 in the retina as well as their clinical association with CSNB, we hypothesize that mGluR6...

The cerebellum is involved in learning of fine motor skills, yet whether presynaptic plasticity contributes to such learning remains elusive. Here we report that the EPAC-PKCε module has a critical role in a presynaptic form of long-term potentiation in the cerebellum and motor behavior in mice. Presynaptic cAMP−EPAC−PKCε signaling cascade induces...

Tests of human brain circuit function typically require fixed equipment in lab environments. We have developed a smartphone-based platform for neurometric testing. This platform, which uses AI models like computer vision, is optimized for at-home use and produces reproducible, robust results on a battery of tests, including eyeblink conditioning, p...

In all species, unipolar brush cells (UBCs) are most abundant in the vestibulocerebellum. Yet, the role of these excitatory interneurons in the cerebellar input stage during visual and vestibular stimulation remains elusive. Here, we review the main morphological and electrophysiological properties of UBCs in the vestibulocerebellum, and we highlig...

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, respir...

In this protocol, all steps required to perform implantation of a Cambridge NeuroTech chronic silicon probe and mini-amp-64 digital headstage, for cerebellar single-unit electrophysiology (above Crus I/II) are described, alongside detailed pictures of the procedure. This protocol starts by describing the steps needed to assemble the probe and nano-...

In this protocol, all steps required to perform implantation of a Cambridge NeuroTech chronic silicon probe and mini-amp-64 digital headstage, for cerebellar single-unit electrophysiology (above Crus I/II) are described, alongside detailed pictures of the procedure. This protocol starts by describing the steps needed to assemble the probe and nano-...

Purpose: To study the effectiveness of high-dose atropine for reducing eye growth in Mendelian myopia in children and mice. Methods: We studied the effect of high-dose atropine in children with progressive myopia with and without a monogenetic cause. Children were matched for age and axial length (AL) in their first year of treatment. We conside...

When the brain is exposed, such as after a craniotomy in neurosurgical procedures, we are provided with the unique opportunity for real-time imaging of brain functionality. Real-time functional maps of the exposed brain are vital to ensuring safe and effective navigation during these neurosurgical procedures. However, current neurosurgical practice...

Tests of human brain circuit function typically require fixed equipment in lab environments. We have developed a smartphone-based platform for neurometric testing. This platform, which uses AI models like computer vision, is optimized for at-home use and produces reproducible, robust results on a battery of tests, including eyeblink conditioning, p...

The delicate balance between generalization and discrimination of responses is crucial for survival in our ever-changing environment. In particular, it is important to understand how stimulus discrimination affects the level of stimulus generalization. For example, when we use non-differential training for Pavlovian eyeblink conditioning to investi...

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 du...

Cerebellar learning is expressed as upbound or downbound changes in simple spike activity of Purkinje cell subpopulations, but the underlying mechanism remains enigmatic. By visualizing murine Purkinje cells with different molecular identities, we demonstrate that the potential for induction of long-term depression is prominent in downbound and min...

Individuals with Neurofibromatosis type 1 (NF1) experience a high degree of motor problems. The cerebellum plays a pivotal role in motor functioning and the NF1 gene is highly expressed in cerebellar Purkinje cells. However, it is not well understood to what extent NF1 affects cerebellar functioning and how this relates to NF1 motor functioning. Th...