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Berciu, C.

Publications and source records attributed to Berciu, C..

2 recordsLinked to original sources

Proteoglycan Clusters as a Site of Coordinated, Multi-Dendritic Plasticity

Experience-dependent learning depends on synaptic plasticity. While plasticity in individual synapses has been extensively investigated, the mechanisms underlying coordinated changes across sets of synapses on multiple dendrites, likely needed to encode effective adaptations to a salient stimulus, are not well understood. The extracellular matrix is uniquely well suited to fulfill this function, as rapid glia-driven remodeling of its local composition powerfully impact synaptic plasticity. We show that extracellular matrix microenvironments, named CS6 clusters, dynamically form around several dendrites in response to sensory stimuli in coincidence to stimulus-driven synaptic plasticity. CS6 clusters, formed by glia-dependent secretion of extracellular matrix components surrounding sets of adjacent dendrites, may represent a novel structure supporting coordinated synaptic plasticity. One Sentence SummaryExtracellular matrix clusters form microenvironments for coordinated multi-dendrite synaptic plasticity.

neuroscience

Postsynaptic serine racemase regulates NMDA receptor function

D-serine is the primary NMDA receptor (NMDAR) co-agonist at mature forebrain synapses and is synthesized by the enzyme serine racemase (SR). However, our understanding of the mechanisms regulating the availability of synaptic D-serine remains limited. Though early studies suggested D-serine is synthesized and released from astrocytes, more recent studies have demonstrated a predominantly neuronal localization of SR. More specifically, recent work intriguingly suggests that SR may be found at the postsynaptic density, yet the functional implications of postsynaptic SR on synaptic transmission are not yet known. Here, we show an age-dependent dendritic and postsynaptic localization of SR and D-serine by immunohistochemistry and electron microscopy in mouse CA1 pyramidal neurons, as well as the presence of SR in human hippocampal synaptosomes. In addition, using a single-neuron genetic approach in SR conditional knockout mice, we demonstrate a cell-autonomous role for SR in regulating synaptic NMDAR function at Schaffer collateral (CA3)-CA1 synapses. Importantly, single-neuron genetic deletion of SR resulted in the elimination of LTP at one month of age. Interestingly, there was a restoration of LTP by two months of age that was associated with an upregulation of synaptic GluN2B. Our findings support a cell-autonomous role for postsynaptic neuronal SR in regulating synaptic NMDAR function and suggests a possible autocrine mode of D-serine action.

neuroscience