Topic: synaptic connectivity

The Allen Institute has launched a new moonshot initiative on human brain health and disease called the Brain Health accelerator. This initiative aims to dramatically accelerate our understanding of human brain structure and function, identify the molecular, cellular and circuit basis of disease progression, and pioneer new therapeutic strategies targeting vulnerable and affected cell types. Our mission focuses on taking a human-centric approach to understanding and treating disease, combining a large-scale open science discovery approach across multiple diseases, AI-based disease modeling, an

Precise synaptic connectivity is a prerequisite for the function of neural circuits, yet individual neurons, taken out of their developmental context, readily form unspecific synapses. How does genetically encoded brain wiring deal with this apparent contradiction? Brain wiring is a developmental growth process that is not only characterized by precision, but also flexibility and robustness. As in any other growth process, cellular interactions are restricted in space and time. Correspondingly, molecular and cellular interactions are restricted to those that 'get to see' each other during deve

Microglia are the immune cells of the brain, and play increasingly appreciated roles in synapse formation, brain plasticity, and cognition. A growing appreciation that the immune system involved in diseases like schizophrenia, epilepsy, and neurodegenerative diseases has led to renewed interest in how microglia regulate synaptic connectivity. Our group previously identified the IL-1 family cytokine Interleukin-33 (IL-33) as a novel regulator of microglial activation and function. I will discuss a mechanism by which microglia regulate synaptic plasticity and long-term memories by engulfing brai

We study the dynamics of (inhibitory) balanced networks at varying (i) the level of symmetry in the synaptic connectivity; and (ii) the ariance of the synaptic efficacies (synaptic gain). We find three regimes of activity. For suitably low synaptic gain, regardless of the level of symmetry, there exists a unique stable fixed point. Using a cavity-like approach, we develop a quantitative theory that describes the statistics of the activity in this unique fixed point, and the conditions for its stability. Increasing the synaptic gain, the unique fixed point destabilizes, and the network exhibits

The structural connectivity matrix of synaptic weights between neurons is a critical determinant of overall network function. However, quantitative links between neural network structure and function are complex and subtle. For example, many networks can give rise to similar functional responses, and the same network can function differently depending on context. Whether certain patterns of synaptic connectivity are required to generate specific network-level computations is largely unknown. Here we introduce a geometric framework for identifying synaptic connections required by steady-state r

The evolution and development of all organisms on earth relies on near-constant gravity. Experimental manipulations can create developmental conditions that have never been encountered during evolution, yet reveal developmental mechanisms based on informative phenotypic outcomes; classically, such experiments include transplantation of developing organs as well as pushing boundaries of environmental conditions.Here, we explore the outcome of Drosophila melanogaster brain development at hyper-gravity 10^2 to 10^3 times greater than conventional gravity on earth. Remarkably, Drosophila pupae ful