Laurens W J Bosman

Laurens W J Bosman
Erasmus MC | Erasmus MC · Department of Neuroscience

PhD
How does the brain, and in particular the cerebellum, adapt actions in response to sensory input?

About

46
Publications
10,258
Reads
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1,658
Citations
Introduction
Motor control involves the integration of sensory and motor pathways that converge in the cerebellum. I focus on in vivo electrophysiology and two-photon calcium imaging to study cerebellar function during sensorimotor integration in health and disease (ataxia). I have a special interest in the communication between the cerebral cortex and the cerebellum during these sensorimotor integration during locomotion and whisker use.
Additional affiliations
November 2010 - March 2012
Netherlands Institute for Neuroscience
Position
  • Sensorimotor integration in the cerebellum
September 2006 - present
Erasmus MC
Position
  • Sensorimotor integration in the cerebellum
January 2006 - August 2006
Technische Universität München
Position
  • Climbing fiber development
Education
February 1998 - October 2002
Vrije Universiteit Amsterdam
Field of study
  • Earth and Life Sciences
September 1993 - February 1998
Leiden University
Field of study
  • Biology

Publications

Publications (46)
Article
Full-text available
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 contribu...
Article
Full-text available
Cerebellar plasticity underlies motor learning. However, how the cerebellum operates to enable learned changes in motor output is largely unknown. We developed a sensory-driven adaptation protocol for reflexive whisker protraction and recorded Purkinje cell activity from crus 1 and 2 of awake mice. Before training, simple spikes of individual Purki...
Article
Full-text available
The cerebellum is involved in the control of voluntary and autonomic rhythmic behaviors, yet it is unclear to what extent it coordinates these in concert. We studied Purkinje cell activity during unperturbed and perturbed respiration in lobules simplex, crus 1, and crus 2. During unperturbed (eupneic) respiration, complex spike and simple spike act...
Article
Full-text available
Significance Coordinated activity of sensory and motor cortices is essential for adjusting movements based on sensory feedback. Sensory and motor cortices communicate directly as well as via the thalamus and also receive indirect input from the cerebellum. We show here that cerebellar activity can affect the amplitude and coherence of fast sensorim...
Article
Full-text available
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 le...
Article
Full-text available
Purkinje cells are the primary processing units of the cerebellar cortex and display molecular heterogeneity that aligns with differences in physiological properties, projection patterns, and susceptibility to disease. In particular, multiple mouse models that feature Purkinje cell degeneration are characterized by incomplete and patterned Purkinje...
Article
Full-text available
The hexanucleotide G 4 C 2 repeat expansion in the first intron of the C9ORF72 gene accounts for the majority of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) cases. Numerous studies have indicated the toxicity of dipeptide repeats (DPRs), which are produced via repeat-associated non-AUG (RAN) translation from the repeat exp...
Article
Full-text available
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a rare neurodegenerative disorder caused by a 55-200 CGG repeat expansion in the 5 untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene. FXTAS is characterized by progressive cerebellar ataxia, Parkinsonism, intention tremors and cognitive decline. The main neuropathological ha...
Article
Full-text available
Rodents engage in active touch using their facial whiskers: they explore their environment by making rapid back-and-forth movements. The fast nature of whisker movements, during which whiskers often cross each other, makes it notoriously difficult to track individual whiskers of the intact whisker field. We present here a novel algorithm, WhiskEras...
Preprint
Full-text available
The cerebellum is involved in cognition next to motor coordination. During complex tasks, climbing fiber input to the cerebellum can deliver seemingly opposite signals, covering both motor and non-motor functions. To elucidate this ambiguity, we hypothesized that climbing fiber activity represents the saliency of inputs leading to action-readiness....
Preprint
The hexanucleotide G 4 C 2 repeat expansion in the first intron of the C9ORF72 gene explains the majority of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) cases. Numerous studies have indicated the toxicity of dipeptide repeats (DPRs) which are produced via repeat-associated non-AUG (RAN) translation from the repeat expansio...
Preprint
Full-text available
Coherence among sensory and motor cortices is indicative of binding of critical functions in perception, motor planning, action and sleep. Evidence is emerging that the cerebellum can impose coherence between cortical areas, but how and when it does so is unclear. Here, we studied coherence between primary somatosensory (S1) and motor (M1) cortices...
Conference Paper
Williams-Beuren syndrome (WBS) is a developmental disorder characterized by distinct facial features, intellectual disability and cardiovascular abnormalities, due to the de novo microdeletion of a region spanning up to 27 genes, including the elastin gene. Cardiovascular abnormalities encountered in WBS are supravalvular aortic stenosis as well as...
Article
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion mutations in the ATXN2 gene, mainly affecting motor neurons in the spinal cord and Purkinje neurons in the cerebellum. While the large expansions were shown to cause SCA2, the intermediate length expansions lead to increased risk for sev...
Preprint
Full-text available
The cerebellum is involved in control of voluntary and autonomic rhythmic behaviors, yet it is largely unclear to what extent it coordinates these in a concerted action. Here, we studied Purkinje cell activity during unperturbed and perturbed respiration in cerebellar lobules simplex, crus 1 and 2. During unperturbed (eupneic) respiration complex s...
Article
Full-text available
Inferior olivary activity causes both short-term and long-term changes in cerebellar output underlying motor performance and motor learning. Many of its neurons engage in coherent subthreshold oscillations and are extensively coupled via gap junctions. Studies in reduced preparations suggest that these properties promote rhythmic, synchronized outp...
Book
The inferior olive in the ventral medulla oblongata provides climbing fibers to Purkinje cells in the cerebellar cortex as well as collaterals to the cerebellar nuclei and thereby exerts a strong impact on cerebellar output. As a consequence, the intrinsic properties of olivary neurons and the synaptic inputs that modify their output are critical f...
Article
Full-text available
Cerebellar Purkinje cells integrate sensory information with motor efference copies to adapt movements to behavioural and environmental requirements. They produce complex spikes that are triggered by the activity of climbing fibres originating in neurons of the inferior olive. These complex spikes can shape the onset, amplitude and direction of mov...
Preprint
Full-text available
Inferior olivary activity causes both short-term and long-term changes in cerebellar output underlying motor adaptation and motor learning, respectively. Many of its neurons engage in coherent subthreshold oscillations and are extensively coupled via gap junctions. Studies in reduced preparations suggest that these properties promote rhythmic, sync...
Preprint
Full-text available
Purkinje cells in the cerebellar cortex fire complex spikes in response to sensory stimulation. These complex spikes are triggered by activity of climbing fibers originating in neurons of the inferior olive. The neurons of the inferior olive are electrically coupled. Strong sensory input has been shown to preferentially recruit coherent climbing fi...
Preprint
Full-text available
Cerebellar plasticity underlies motor learning. However, how the cerebellum operates to enable learned changes in motor output is largely unknown. We developed a sensory-driven adaptation protocol for reflexive whisker protraction and recorded Purkinje cell activity from crus 1 and 2 of awake mice. Before training, simple spikes of individual Purki...
Preprint
Full-text available
Unstable expansions in the Q22-polyglutamine domain of human ATXN2 mediate risks for motor neuron diseases such as ALS/FTLD or cause the autosomal dominant Spinocerebellar Ataxia type 2 (SCA2), but the pathogenesis is not understood and models are unavailable. We generated a novel knock-in mouse line with CAG100 expansion in Atxn2 , transmitted uns...
Article
Full-text available
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...
Conference Paper
Full-text available
The rodent whisker system is a prominent experimental subject for the study of sensorimotor integration and active sensing. As a result of improved video-recording technology and progressively better neurophysiological methods, there is now the prospect of precisely analyzing the intact vibrissal sensori-motor system. The vibrissae and snout analyz...
Conference Paper
Mice heavily rely on their whiskers to orient themselves in their environment and to determine the position, size and texture of objects. They have large facial whiskers that can be moved rhythmically. In line with its behavioural importance, a substantial part of the mouse brain is devoted to the whisker system. Although most attention has been di...
Article
Full-text available
Synaptic and intrinsic processing in Purkinje cells, interneurons and granule cells of the cerebellar cortex have been shown to underlie various relatively simple, single-joint, reflex types of motor learning, including eyeblink conditioning and adaptation of the vestibulo-ocular reflex. However, to what extent these processes contribute to more co...
Article
Full-text available
Due to the uniform cyto-architecture of the cerebellar cortex, its overall physiological characteristics have traditionally been considered to be homogeneous. In this study, we show in awake mice at rest that spiking activity of Purkinje cells, the sole output cells of the cerebellar cortex, differs between cerebellar modules and correlates with th...
Article
Full-text available
Whisker-based object localization requires activation and plasticity of somatosensory and motor cortex. These parts of the cerebral cortex receive strong projections from the cerebellum via the thalamus, but it is unclear whether and to what extent cerebellar processing may contribute to such a sensorimotor task. Here, we subjected knock-out mice,...
Article
Full-text available
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability. Patients with FXS do not only suffer from cognitive problems, but also from abnormalities/deficits in procedural memory formation. It has been proposed that a lack of fragile X mental retardation protein (FMRP) leads to altered long-term plasticity by deregulatio...
Chapter
Full-text available
The inferior olive provides all climbing fibers to the Purkinje cells in the cerebellar cortex and thereby has a strong impact on cerebellar output. As a consequence, the integration of inputs to olivary neurons as well as their intrinsic properties are critical for cerebellar function. In this chapter, all issues that are relevant for their ultima...
Article
Full-text available
Neurons are generally considered to communicate information by increasing or decreasing their firing rate. However, in principle, they could in addition convey messages by using specific spatiotemporal patterns of spiking activities and silent intervals. Here, we review expanding lines of evidence that such spatiotemporal coding occurs in the cereb...
Article
The cerebellar cortex is crucial for sensorimotor integration. Sensorimotor inputs converge on cerebellar Purkinje cells via two afferent pathways: the climbing fibre pathway triggering complex spikes, and the mossy fibre–parallel fibre pathway, modulating the simple spike activities of Purkinje cells. We used, for the first time, the mouse whisker...
Article
Full-text available
Primary sensory cortical areas continuously receive thalamic inputs that arrive at different frequencies depending on the amount of sensory activity. The cortical response to repeated sensory stimuli rapidly adapts and different frequencies recruit cortical neuronal networks to different extents. GABAergic inhibition limits the spread of excitation...
Article
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During the eye-opening development phase in mice, in primary visual cortex, changes in GABAA postsynaptic receptor function appear to occur in a highly regulated manner. In particular, significant correlation [1,2] exists between the developmental reduction in the duration of inhibitory postsynaptic currents (IPSCs) and the concom-itant development...
Article
Elimination of redundant synapses and strengthening of the surviving ones are crucial steps in the development of the nervous system. Both processes can be readily followed at the climbing fiber to Purkinje cell synapse in the cerebellum. Shortly after birth, around five equally strong climbing fiber synapses are established. Subsequently, one of t...
Article
Full-text available
During the developmental formation of neuronal circuits, redundant synapses are eliminated and persisting synapses strengthened. In the immature cerebellum, climbing fiber-Purkinje cell synapses undergo a pronounced synaptic rewiring, from a multiple innervation around birth to a mono-innervation in adults. An early stage of this process consists i...
Article
Full-text available
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...
Article
Full-text available
There is a large variation in structurally and functionally different GABA(A) receptor subtypes. The expression pattern of GABA(A) 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 GABA(A) receptor alpha1 subunit...
Article
Full-text available
Developmental upregulation of the GABAA receptor alpha1 subunit causes a faster decay of GABAergic inhibitory postsynaptic currents (IPSCs) in the visual cortex around the time of eye opening. In alpha1 deficient mice, a juvenile type of GABAA receptors is retained during maturation. As a result the decay time of the IPSCs is longer in alpha1-/- mi...
Article
Full-text available
The subunit composition of the GABAA receptor determines the decay time of the GABAergic inhibitory postsynaptic current (IPSC). In mice in which the α1 subunit is deleted, the decay time is longer than in wild-type mice, while the spatial spread of activity in the visual cortex following local stimulation is reduced. Using a simple network model o...
Article
Changes in subunit composition of N-methyl-d-aspartate (NMDA) receptors have been reported to be affected by visual experience and may therefore form a major aspect of neuronal plasticity in the CNS during development. In contrast, putative alterations in the expression and functioning of the inhibitory GABAA receptor around eye opening have not be...
Article
Full-text available
During the female reproductive cycle, hypothalamic oxytocin (OT) neurons undergo sharp changes in excitability. In lactating mammals, bursts of electrical activity of OT neurons result in the release of large amounts of OT in the bloodstream, which causes milk ejection. One hypothesis is that OT neurons regulate their own firing activity and that o...
Article
Each GABA(A) receptor consists of two alpha and three other subunits. The spatial and temporal distribution of different alpha subunit isomeres expressed by the CNS is highly regulated. Here we study changes in functional contribution of different alpha subunits during neonatal development in rat visual cortex. First, we characterized postsynaptic...
Article
DuringDictyosteliumdevelopment, the differentiation inducing factor (DIF) triggers expression of the prestalk geneecmBand induces stalk cell differentiation, a form of programmed cell death. The effects of DIF are mediated by a sustained increase in cytosolic Ca2+levels. The Ca2+ATPase inhibitor BHQ causes a similar rise in Ca2+levels and also indu...

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Project (1)
Project
The physiology and anatomy of the inferior olive lend themselves extraordinarily well to dynamical systems modeling. We are pushing experimentally and theoretically for an understanding of this essential part of the cerebellar system compatible with our best experimental knowledge.