Gain control of sensory input across polysynaptic circuitries in mouse visual cortex by a single G protein-coupled receptor type (5-HT).

Response gain is a crucial means by which modulatory systems control the impact of sensory input. In the visual cortex, the serotonergic 5-HT receptor is key in such modulation. However, due to its expression across different cell types and lack of methods that allow for specific activation, the underlying network mechanisms remain unsolved.

Separable gain control of ongoing and evoked activity in the visual cortex by serotonergic input.

Controlling gain of cortical activity is essential to modulate weights between internal ongoing communication and external sensory drive. Here, we show that serotonergic input has separable suppressive effects on the gain of ongoing and evoked visual activity. We combined optogenetic stimulation of the dorsal raphe nucleus (DRN) with wide-field calcium imaging, extracellular recordings, and iontophoresis of serotonin (5-HT) receptor antagonists in the mouse visual cortex.

CaMello-XR enables visualization and optogenetic control of G signals and receptor trafficking in GPCR-specific domains.

The signal specificity of G protein-coupled receptors (GPCRs) including serotonin receptors (5-HT-R) depends on the trafficking and localization of the GPCR within its subcellular signaling domain. Visualizing traffic-dependent GPCR signals in neurons is difficult, but important to understand the contribution of GPCRs to synaptic plasticity. We engineered CaMello (Ca-melanopsin-local-sensor) and CaMello-5HT for visualization of traffic-dependent Ca signals in 5-HT-R domains.

In Vivo Regulation of Oligodendrocyte Precursor Cell Proliferation and Differentiation by the AMPA-Receptor Subunit GluA2.

The functional role of AMPA receptor (AMPAR)-mediated synaptic signaling between neurons and oligodendrocyte precursor cells (OPCs) remains enigmatic. We modified the properties of AMPARs at axon-OPC synapses in the mouse corpus callosum in vivo during the peak of myelination by targeting the GluA2 subunit. Expression of the unedited (Ca permeable) or the pore-dead GluA2 subunit of AMPARs triggered proliferation of OPCs and reduced their differentiation into oligodendrocytes.

Glutamate Activates AMPA Receptor Conductance in the Developing Schwann Cells of the Mammalian Peripheral Nerves.

Schwann cells (SCs) are myelinating cells of the PNS. Although SCs are known to express different channels and receptors on their surface, little is known about the activation and function of these proteins. Ionotropic glutamate receptors are thought to play an essential role during development of SC lineage and during peripheral nerve injury, so we sought to study their functional properties.

Different patterns of neuronal activity trigger distinct responses of oligodendrocyte precursor cells in the corpus callosum.

In the developing and adult brain, oligodendrocyte precursor cells (OPCs) are influenced by neuronal activity: they are involved in synaptic signaling with neurons, and their proliferation and differentiation into myelinating glia can be altered by transient changes in neuronal firing. An important question that has been unanswered is whether OPCs can discriminate different patterns of neuronal activity and respond to them in a distinct way. Here, we demonstrate in brain slices that the pattern of neuronal activity determines the functional changes triggered at synapses between axons and OPCs.

N- and L-Type Voltage-Gated Calcium Channels Mediate Fast Calcium Transients in Axonal Shafts of Mouse Peripheral Nerve.

In the peripheral nervous system (PNS) a vast number of axons are accommodated within fiber bundles that constitute peripheral nerves. A major function of peripheral axons is to propagate action potentials along their length, and hence they are equipped with Na(+) and K(+) channels, which ensure successful generation, conduction and termination of each action potential. However little is known about Ca(2+) ion channels expressed along peripheral axons and their possible functional significance.