Microglia: Dynamic Mediators of Synapse Development and Plasticity
2015; Elsevier BV; Volume: 36; Issue: 10 Linguagem: Inglês
10.1016/j.it.2015.08.008
ISSN1471-4981
AutoresYuwen Wu, Lasse Dissing‐Olesen, Brian A. MacVicar, Beth Stevens,
Tópico(s)Neuroscience and Neuropharmacology Research
ResumoDuring brain development, complement-mediated engulfment of synapses by microglia is required for activity-dependent refinement of neuronal circuits. Microglia processes constantly move as they survey the surrounding environment. Increased neuronal activity triggers enhanced surveillance, which is characterized by ATP-mediated outgrowth of microglial processes. Microglia can modify activity-dependent changes in synaptic strength between neurons that underlie memory and learning using classical immunological signaling pathways involving cytokine release and NADPH oxidase activation. Altered immune system function in the brain triggered by inflammatory responses or immune dysregulation can lead to cognitive dysfunction and behavioral abnormalities. Neuronal communication underlies all brain activity and the genesis of complex behavior. Emerging research has revealed an unexpected role for immune molecules in the development and plasticity of neuronal synapses. Moreover microglia, the resident immune cells of the brain, express and secrete immune-related signaling molecules that alter synaptic transmission and plasticity in the absence of inflammation. When inflammation does occur, microglia modify synaptic connections and synaptic plasticity required for learning and memory. Here we review recent findings demonstrating how the dynamic interactions between neurons and microglia shape the circuitry of the nervous system in the healthy brain and how altered neuron–microglia signaling could contribute to disease. Neuronal communication underlies all brain activity and the genesis of complex behavior. Emerging research has revealed an unexpected role for immune molecules in the development and plasticity of neuronal synapses. Moreover microglia, the resident immune cells of the brain, express and secrete immune-related signaling molecules that alter synaptic transmission and plasticity in the absence of inflammation. When inflammation does occur, microglia modify synaptic connections and synaptic plasticity required for learning and memory. Here we review recent findings demonstrating how the dynamic interactions between neurons and microglia shape the circuitry of the nervous system in the healthy brain and how altered neuron–microglia signaling could contribute to disease. refers to the deprivation of visual experiences. This is generally achieved by housing juvenile mice in complete darkness, which increases dendritic spine turnover in the visual cortex. are postsynaptic neuronal structures that are correlated with neuronal synapses. Physically they appear as a protrusion along neuronal dendrites. refers to the toxic effect that certain neurotransmitters (e.g., glutamate) can exert on excitatory cells (e.g., neurons) and eventually leads to cell death. are connections between neurons that allow for rapid communication via release of neurotransmitters (e.g., glutamate) from a presynaptic neuron and consequently activation of receptors on a postsynaptic neuron. In this review, ‘synapse’ will refer only to neuronal synapses and not immunological synapses. refers to the neurons of the retina (retinal ganglion cells) projecting to and synapsing with postsynaptic relay neurons in the dorsal lateral geniculate nucleus of the visual thalamus. This system has played a crucial role in elucidating mechanisms of synaptic pruning due to its stereotyped development and relative ease of manipulation. is the process by which synapses increase or decrease in strength following alterations in neuronal activity. For example, long-term potentiation (LTP) and long-term depression (LTD) are persistent changes in synaptic strength following high frequency stimulation or a prolonged patterned stimulus, respectively. LTP leads to strengthened synapses, while LTD results in synaptic weakening. Synaptic plasticity mechanisms are thought to underlie learning and memory. is the developmental process by which immature or extraneous synapses are eliminated. This process is essential in sculpting of a functional and mature neuronal circuit. Low activity synapses are preferentially pruned over highly active synapses. refers to a feedback mechanism whereby postsynaptic AMPA receptor insertion or deletion is used to scale synaptic strength up or down to ensure consistent electrical output from synaptic inputs. is a technique that allows access to the intracellular environment of a cell through a glass micropipette and thereby enables the possibility of controlling and recording the cells electrical properties.
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