Synaptic
synaptic communication
Brain network communication: concepts, models and applications
Understanding communication and information processing in nervous systems is a central goal of neuroscience. Over the past two decades, advances in connectomics and network neuroscience have opened new avenues for investigating polysynaptic communication in complex brain networks. Recent work has brought into question the mainstay assumption that connectome signalling occurs exclusively via shortest paths, resulting in a sprawling constellation of alternative network communication models. This Review surveys the latest developments in models of brain network communication. We begin by drawing a conceptual link between the mathematics of graph theory and biological aspects of neural signalling such as transmission delays and metabolic cost. We organize key network communication models and measures into a taxonomy, aimed at helping researchers navigate the growing number of concepts and methods in the literature. The taxonomy highlights the pros, cons and interpretations of different conceptualizations of connectome signalling. We showcase the utility of network communication models as a flexible, interpretable and tractable framework to study brain function by reviewing prominent applications in basic, cognitive and clinical neurosciences. Finally, we provide recommendations to guide the future development, application and validation of network communication models.
Molecular Logic of Synapse Organization and Plasticity
Connections between nerve cells called synapses are the fundamental units of communication and information processing in the brain. The accurate wiring of neurons through synapses into neural networks or circuits is essential for brain organization. Neuronal networks are sculpted and refined throughout life by constant adjustment of the strength of synaptic communication by neuronal activity, a process known as synaptic plasticity. Deficits in the development or plasticity of synapses underlie various neuropsychiatric disorders, including autism, schizophrenia and intellectual disability. The Siddiqui lab research program comprises three major themes. One, to assess how biochemical switches control the activity of synapse organizing proteins, how these switches act through their binding partners and how these processes are regulated to correct impaired synaptic function in disease. Two, to investigate how synapse organizers regulate the specificity of neuronal circuit development and how defined circuits contribute to cognition and behaviour. Three, to address how synapses are formed in the developing brain and maintained in the mature brain and how microcircuits formed by synapses are refined to fine-tune information processing in the brain. Together, these studies have generated fundamental new knowledge about neuronal circuit development and plasticity and enabled us to identify targets for therapeutic intervention.
Modulation of oligodendrocyte development and myelination by voltage-gated Ca++ channels
The oligodendrocyte generates CNS myelin, which is essential for normal nervous system function. Thus, investigating the regulatory and signaling mechanisms that control its differentiation and the production of myelin is relevant to our understanding of brain development and of adult pathologies such as multiple sclerosis. We have recently established that the activity of voltage-gated Ca++ channels is crucial for the adequate migration, proliferation and maturation of oligodendrocyte progenitor cells (OPCs). Furthermore, we have found that voltage-gated Ca++ channels that function in synaptic communication between neurons also mediate synaptic signaling between neurons and OPCs. Thus, we hypothesize that voltage-gated Ca++ channels are central components of OPC-neuronal synapses and are the principal ion channels mediating activity-dependent myelination.