A tripartite circRNA/mRNA/miRNA interaction regulates glutamatergic signaling in the mouse brain.

Functional studies of circular RNAs (circRNAs) began quite recently, and few data exist on their function in vivo. Here, we have generated a knockout (KO) mouse model to study circDlc1(2), a circRNA highly expressed in the prefrontal cortex and striatum. The loss of circDlc1(2) led to the upregulation of glutamatergic-response-associated genes in the striatal tissue, enhanced excitatory synaptic transmission in neuronal cultures, and hyperactivity and increased stereotypies in mice.

Microglia at the Tripartite Synapse during Postnatal Development: Implications for Autism Spectrum Disorders and Schizophrenia.

Synapses are the fundamental structures of neural circuits that control brain functions and behavioral and cognitive processes. Synapses undergo formation, maturation, and elimination mainly during postnatal development via a complex interplay with neighboring astrocytes and microglia that, by shaping neural connectivity, may have a crucial role in the strengthening and weakening of synaptic functions, that is, the functional plasticity of synapses. Indeed, an increasing number of studies have unveiled the roles of microglia and astrocytes in synapse formation, maturation, and elimination as well as in regulating synaptic function.

Human iPSC-Derived Cortical Neurons Display Homeostatic Plasticity.

Maintaining the excitability of neurons and circuits is fundamental for healthy brain functions. The global compensatory increase in excitatory synaptic strength, in response to decreased activity, is one of the main homeostatic mechanisms responsible for such regulation. This type of plasticity has been extensively characterized in rodents in vivo and in vitro, but few data exist on human neurons maturation.

What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior.

Microglia are dynamic cells, constantly surveying their surroundings and interacting with neurons and synapses. Indeed, a wealth of knowledge has revealed a critical role of microglia in modulating synaptic transmission and plasticity in the developing brain. In the past decade, novel pharmacological and genetic strategies have allowed the acute removal of microglia, opening the possibility to explore and understand the role of microglia also in the adult brain.

Antibiotics Treatment Modulates Microglia-Synapses Interaction.

'Dysbiosis' of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked to pathological alteration of brain function and behavior. Moreover, gut microbiota composition constantly controls microglia maturation, as revealed by morphological observations and gene expression analysis. However, it is unclear whether microglia functional properties and crosstalk with neurons, known to shape and modulate synaptic development and function, are influenced by the gut microbiota.

Microglia control glutamatergic synapses in the adult mouse hippocampus.

Microglia cells are active players in regulating synaptic development and plasticity in the brain. However, how they influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice.