Synaptic pruning

…The postdoc leads projects on synaptic pruning and connections during adolescence using virus-based neural circuit mapping with molecular and pharmacological tools, works with computat

Computational neuroscience increasingly leverages gradient descent (GD) for training artificial neural network (ANN) models of the brain. GD’s advantage is that it is very effective at learning difficult tasks. This is important for the role of computational models as the interface between theory and empirical data (Levenstein et al., 2023), since models that can learn realistic tasks from realistic, high-dimensional inputs can be more directly compared to experimental data (Doerig et al., 2023). However, GD produces ANNs that are poor phenomenological fits to biology, making them less relevan

…an important role for microglia in synaptic pruning and loss. Nevertheless, it remains to be determined whether and how microglia are involved in the process of synapse formation under physiologic conditions. We hypothesize that microglia serve as a link between pre- and post-synapse by sensing neurotransmitter release at highly active pre-synaptic sites and actively modulate the formation of new dendritic spines.To examine this relationship, we target microglia-synapse communicatio

Mucopolysaccharidosis type IIIA (MPS-IIIA) is a rare genetic metabolism disorder, belonging to the class of Lysosomal Storage Disorders (LSD). MPS-IIIA is caused by a mutation in the gene SGSH, leading to lysosomal enzyme sulfamidase deficiency and impaired degradation of heparan sulfate. Although the disease manifests during early childhood as an autistic spectrum disorder (ASD), the causes of ASD in MPS-IIIA are only poorly explored. Using a genetic mouse model of MPS-IIIA, we have recently discovered that these autistic-like behavioural symptoms (ALBs), which are known to be subtly regula

…it has been proposed that excessive synaptic pruning may contribute to the observed reduction in gray matter thickness and synapse density in SCZ patients. We modelled synaptic pruning using patient-derived stem-cell-based forebrain organoids, containing innately developed microglia, and assessed mic

…neuronal maturation and refining synaptic connections. These cells are emerging as highly metabolically flexible, able to oxidize a variety of nutrients to meet their energy demand. Accumulating evidence points towards the involvement of metabolism and differential substrates catabolism in the regulation of immune cells. Lactate, which is abundant in the brain and sustains synaptic activity, also dictates responses of peripheral immune cells. However, the physiologi

Alzheimer's Disease (AD), responsible for the majority of dementia cases, is a progressive neurodegenerative disorder marked by amyloid-β accumulation, tauopathy, neuroinflammation, and cognitive decline. Parallel to this cognitive decline, the number of memory-related neurons (engram cells) is reduced in the APPswe/PSEN1dE9 mouse model for slow-progressing AD, crossed with a genetically modified mouse line that allows us to visualize engram neurons (Arc::dVenus mice). We hypothesize that aberrant microglial modulation of engram cells might contribute to the AD-related changes in engram and co

…critically modulates hippocampal synaptic plasticity and cognitive function in adult mice under physiological conditions. Since cytokines such as type I interferons are implicated in modulation of neurogenesis and brain development, in this work we started to

Long-term depression (LTD) is an activity-dependent decrease of synaptic strength. This depressed state is transient, initiating either a re-potentiation or suppression, referred to as pruning, of the synapse within hours to days following the LTD induction. Nevertheless, the precise relationship between LTD and synaptic pruning remains incompletely elucidated. Through the integration of various imaging techniques and electrophysiology, we have identified essential factors that link NMDAR-dependent LTD to synaptic pruning. The molecular alterations pivotal for the induction of LTD must persist

Microglia are the brain macrophages, eliciting multifaceted functions to maintain brain homeostasis across lifetime. To achieve this, microglia are able to sense a plethora of signals in their close environment. In the lab, we investigate the effect of nutrients on microglia function for several reasons: 1) Microglia express all the cellular machinery required to sense nutrients; 2) Eating habits have changed considerably over the last century, towards diets rich in fats and sugars; 3) This so-called "Western diet" is accompanied by an increase in the occurrence of neuropathologies, in which m

The structure and function of biological neural networks are the result of biological “construction rules”, physical limits, stochasticity, developmental noise, and learning. The nature of these building rules and the resulting architectures are fundamental to our understanding of neuro-developmental plans and the structure and function of neural circuits. The detailed reconstruction of connectomes makes it possible to study their design; Recent reconstruction of connectomes during different developmental stages in C. elegans allows for characterization of their development. We present a class

The human visual cortex is modular, parcellated into a hierarchy of visual areas (V1, V2, V3, etc.) that abut each other in the brain. The areas are each retinotopically organized with several characteristing higher-level organizational features --- a notable example is that the polar angle of the retinotopic maps alternates (is mirrored) across area boundaries. Normative (task-trained) models of the dorsal visual stream capture important aspects of neural tuning, but typically only involve feedforward connections and already assume a hierarchical organization of a discrete set of areas. They

…called microglia, in sculpting of synaptic connections during development and their relevance to autism, schizophrenia and other brain disorders. Her recent work revealed a key role for microglia and a group of immune related molecules called complement in normal developmental synaptic pruning, a normal process required to establish precise brain wiring. Emerging evidence suggests aberrant regulation of this pruning pathway may contribute to synaptic and cognitive dysfunction in a host of brain disorders,

…noise could play a functional role in synaptic pruning, allo