Publications by authors named "Tim Kroon"

The medial entorhinal cortex (MEC) contains specialized cell types whose firing is tuned to aspects of an animal's position and orientation in the environment, reflecting a neuronal representation of space. The spatially tuned firing properties of these cells quickly emerge during the third postnatal week of development in rodents. Spontaneous synchronized network activity (SSNA) has been shown to play a crucial role in the development of neuronal circuits prior to week 3.

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  • ChAT-VIP interneurons, a special type of neuron in the brain's cortex, play a key role in signaling by directly exciting nearby neurons using acetylcholine (ACh) for fast communication.
  • These neurons are connected to both interneurons and pyramidal neurons across different layers of the medial prefrontal cortex (mPFC), highlighting their widespread influence.
  • Importantly, ChAT-VIP neurons help regulate attention behaviors in a unique way compared to other ACh sources in the brain, indicating their distinct functional role in cognitive processes.
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  • Group I metabotropic glutamate receptors (mGluRs) are key players in brain signaling and are being studied as potential targets for treating neuropsychiatric and developmental disorders.
  • Research primarily focused on rodent brains has begun exploring how these receptors impact human neocortex microcircuits, revealing significant effects on neuron activity.
  • Activation of group I mGluRs increases inhibitory action from Martinotti cells, affects other interneurons differently, and depresses excitatory synapses in human pyramidal neurons, suggesting a crucial shift in the balance of excitation and inhibition in the brain.
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Mammalian neocortex is a highly layered structure. Each layer is populated by distinct subtypes of principal cells that are born at different times during development. While the differences between principal cells across layers have been extensively studied, it is not known how the developmental profiles of neurons in different layers compare.

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How neuronal connections are established and organized into functional networks determines brain function. In the mammalian cerebral cortex, different classes of GABAergic interneurons exhibit specific connectivity patterns that underlie their ability to shape temporal dynamics and information processing. Much progress has been made toward parsing interneuron diversity, yet the molecular mechanisms by which interneuron-specific connectivity motifs emerge remain unclear.

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  • Inhibitory pathways involving different types of interneurons, like basket cells (BCs) and Martinotti cells (MCs), influence the activity of neocortical pyramidal neurons, with BCs providing fast and MCs providing delayed lateral inhibition.
  • Acetylcholine plays a critical role in modulating cortical functions and has a notable effect on MC firing by enhancing and speeding up the lateral inhibition mediated by MCs specifically, rather than BCs.
  • The study demonstrates that cholinergic inputs act through specific receptors to recruit more MCs, which helps emphasize particular neural circuits in the neocortex, a mechanism that is also present in humans.
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  • Presynaptic cannabinoid (CB1R) and metabotropic glutamate receptors (mGluR2/3) play a key role in reducing synaptic strength by inhibiting neurotransmitter release.
  • The research highlights a pathway where the extracellular signal-regulated kinase (ERK) activates the inhibition of secretion through the phosphorylation of a protein called Munc18-1.
  • This phosphorylation leads to Munc18-1 degradation, acting as a negative feedback mechanism that regulates synaptic strength, revealing that blocking this phosphorylation can enhance synaptic transmission.
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Synaptic plasticity requires remodeling of the actin cytoskeleton. Although two actin isoforms, β- and γ-actin, are expressed in dendritic spines, the specific contribution of γ-actin in the expression of synaptic plasticity is unknown. We show that synaptic γ-actin levels are regulated by the E3 ubiquitin ligase TRIM3.

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Developing networks in the immature nervous system and in cellular cultures are characterized by waves of synchronous activity in restricted clusters of cells. Synchronized activity in immature networks is proposed to regulate many different developmental processes, from neuron growth and cell migration, to the refinement of synapses, topographic maps, and the mature composition of ion channels. These emergent activity patterns are not present in all cells simultaneously within the network and more immature "silent" cells, potentially correlated with the presence of silent synapses, are prominent in different networks during early developmental periods.

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Munc18-1 is a soluble protein essential for synaptic transmission. To investigate the dynamics of endogenous Munc18-1 in neurons, we created a mouse model expressing fluorescently tagged Munc18-1 from the endogenous munc18-1 locus. We show using fluorescence recovery after photobleaching in hippocampal neurons that the majority of Munc18-1 trafficked through axons and targeted to synapses via lateral diffusion together with syntaxin-1.

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Brain function and behavior undergo significant plasticity and refinement, particularly during specific critical and sensitive periods. In autistic and intellectual disability (ID) neurodevelopmental disorders (NDDs) and their corresponding genetic mouse models, impairments in many neuronal and behavioral phenotypes are temporally regulated and in some cases, transient. However, the links between neurobiological mechanisms governing typically normal brain and behavioral development (referred to also as "neurotypical" development) and timing of NDD impairments are not fully investigated.

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A hallmark pattern of activity in developing nervous systems is spontaneous, synchronized network activity. Synchronized activity has been observed in intact spinal cord, brainstem, retina, cortex and dissociated neuronal culture preparations. During periods of spontaneous activity, neurons depolarize to fire single or bursts of action potentials, activating many ion channels.

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