Input-dependent segregation of visual and somatosensory circuits in the mouse superior colliculus.

Whereas sensory perception relies on specialized sensory pathways, it is unclear whether these pathways originate as modality-specific circuits. We demonstrated that somatosensory and visual circuits are not by default segregated but require the earliest retinal activity to do so. In the embryo, somatosensory and visual circuits are intermingled in the superior colliculus, leading to cortical multimodal responses to whisker pad stimulation.

Spontaneous Thalamic Activity Modulates the Cortical Innervation of the Primary Visual Nucleus of the Thalamus.

Sensory processing relies on the correct development of thalamocortical loops. Visual corticothalamic axons (CTAs) invade the dorsolateral geniculate nucleus (dLGN) of the thalamus in early postnatal mice according to a regulated program that includes activity-dependent mechanisms. Spontaneous retinal activity influences the thalamic incursion of CTAs, yet the perinatal thalamus also generates intrinsic patterns of spontaneous activity whose role in modulating afferent connectivity remains unknown.

Spontaneous activity in developing thalamic and cortical sensory networks.

Developing sensory circuits exhibit different patterns of spontaneous activity, patterns that are related to the construction and refinement of functional networks. During the development of different sensory modalities, spontaneous activity originates in the immature peripheral sensory structures and in the higher-order central structures, such as the thalamus and cortex. Certainly, the perinatal thalamus exhibits spontaneous calcium waves, a pattern of activity that is fundamental for the formation of sensory maps and for circuit plasticity.

Prenatal activity from thalamic neurons governs the emergence of functional cortical maps in mice.

The mammalian brain's somatosensory cortex is a topographic map of the body's sensory experience. In mice, cortical barrels reflect whisker input. We asked whether these cortical structures require sensory input to develop or are driven by intrinsic activity.

Impact of thalamocortical input on barrel cortex development.

The development of cortical maps requires the balanced interaction between genetically determined programs and input/activity-dependent signals generated spontaneously or triggered from the environment. The somatosensory pathway of mice provides an excellent scenario to study cortical map development because of its highly organized cytoarchitecture, known as the barrel field. This precise organization makes evident even small alterations in the cortical map layout.

Prenatal thalamic waves regulate cortical area size prior to sensory processing.

The cerebral cortex is organized into specialized sensory areas, whose initial territory is determined by intracortical molecular determinants. Yet, sensory cortical area size appears to be fine tuned during development to respond to functional adaptations. Here we demonstrate the existence of a prenatal sub-cortical mechanism that regulates the cortical areas size in mice.

Contact repulsion controls the dispersion and final distribution of Cajal-Retzius cells.

Cajal-Retzius (CR) cells play a fundamental role in the development of the mammalian cerebral cortex. They control the formation of cortical layers by regulating the migration of pyramidal cells through the release of Reelin. The function of CR cells critically depends on their regular distribution throughout the surface of the cortex, but little is known about the events controlling this phenomenon.

Actomyosin contraction at the cell rear drives nuclear translocation in migrating cortical interneurons.

Neuronal migration is a complex process requiring the coordinated interaction of cytoskeletal components and regulated by calcium signaling among other factors. Migratory neurons are polarized cells in which the largest intracellular organelle, the nucleus, has to move repeatedly. Current views support a central role for pulling forces that drive nuclear movement.

Biased selection of leading process branches mediates chemotaxis during tangential neuronal migration.

Current models of chemotaxis during neuronal migration and axon guidance propose that directional sensing relies on growth cone dynamics. According to this view, migrating neurons and growing axons are guided to their correct targets by steering the growth cone in response to attractive and repulsive cues. Here, we have performed a detailed analysis of the dynamic behavior of individual neurons migrating tangentially in telencephalic slices using high-resolution time-lapse videomicroscopy.

Chemokine signaling controls intracortical migration and final distribution of GABAergic interneurons.

Functioning of the cerebral cortex requires the coordinated assembly of circuits involving glutamatergic projection neurons and GABAergic interneurons. Although much is known about the migration of interneurons from the subpallium to the cortex, our understanding of the mechanisms controlling their precise integration within the cortex is still limited. Here, we have investigated in detail the behavior of GABAergic interneurons as they first enter the developing cortex by using time-lapse videomicroscopy, slice culture, and in utero experimental manipulations and analysis of mouse mutants.

Neurons in motion: same principles for different shapes?

The special conformation of the developing nervous system, in which progenitor zones are largely confined to the lumen of the neural tube, places neuronal migration as one of the most fundamental processes in brain development. Previous studies have shown that different neuronal types adopt distinct morphological modes of migration in the developing brain, indicating that neuronal migration might be a diverse process. Here, we review recent data on the molecular mechanisms underlying neuronal migration that suggest that similar signaling principles are responsible for the frequently variable morphology of different types of migrating neuron.

Polarized increase of calcium and nucleokinesis in tangentially migrating neurons.

Cortical interneurons originate from the ganglionic eminences and reach their final position in the cortex via tangential migratory routes. The mechanisms of this migration are poorly understood. Here we have performed confocal time-lapse analysis of cell movement in the intermediate zone of embryonic mouse cortical slices in order to directly visualize their mode of migration.

Receptor-activated calcium signals in tangentially migrating cortical cells.

Recent studies have shown that the two main types of cortical neurons, pyramidal and nonpyramidal, have different origins and use different migratory routes--radial and tangential respectively. The role of neurotransmitters in radial migration is well known; however, there are no data about their effect on intracellular calcium--[Ca(2+)](i)--in tangentially migrating cells. We have performed ratiometric and confocal calcium imaging of 1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine labelled tangentially migrating neurons in the intermediate zone cells of fetal rat coronal slices.

No evidence for bradykinin B1 receptors in rat dorsal root ganglion neurons.

Bradykinin receptors are believed to contribute to hyperalgesia under conditions of neuropathic pain. Using calcium imaging we investigated responses to B1 and B2 agonists on isolated rat dorsal root ganglion neurons. No response to the B1 agonist was detected, whereas 12% of neurons responded to the B2 agonist.

Cajal-Retzius cells in early postnatal mouse cortex selectively express functional metabotropic glutamate receptors.

Glutamate receptors have been linked to the regulation of several developmental events in the CNS. By using cortical slices of early postnatal mice, we show that in layer I cells, glutamate produces intracellular calcium ([Ca(2+)](i)) elevations mediated by ionotropic and metabotropic glutamate receptors (mGluRs). The contribution of mGluRs to these responses was demonstrated by application of tACPD, an agonist to groups I and II mGluRs, which evoked [Ca(2+)](i) increases that could be reversibly blocked by MCPG, an antagonist to groups I and II mGluRs.

Synchronous glucose-dependent [Ca(2+)](i) oscillations in mouse pancreatic islets of Langerhans recorded in vivo.

Using microfluorescence in combination with image-analysis techniques we monitored intracellular calcium ([Ca(2+)](i)) dynamics in mouse islets of Langerhans loaded with fura-2 and recorded in vivo. [Ca(2+)](i) oscillates in the glycaemias range 5-10 mM, the duration of the oscillations being directly proportional to the blood glucose concentration. The analysis of different areas within the same islet shows that [Ca(2+)](i) oscillations are synchronous throughout the islet.

Functional NMDA and GABAA receptors in pioneer neurons of the cortical marginal zone.

Transient pioneer neurons in the neocortical marginal zone generate an early corticofugal axonal projection at E12-E16 (Meyer et al. 1998). We have analysed the functional activity of glutamate and GABA receptors in such cells by measuring changes in intracellular calcium concentrations ([Ca2+]i).

Glucose-dependent stimulatory effect of glucagon-like peptide 1(7-36) amide on the electrical activity of pancreatic beta-cells recorded in vivo.

The stimulatory effect of the glucagon-like peptide (GLP)-1(7-36) amide on electrical activity in pancreatic b-cells recorded in vivo was studied. The injection of GLP-1 produces a lengthening of the active phase with respect to the silent phase, leading to a stimulation of insulin release, which produces a secondary decrease in blood glucose concentration and eventually, to the hyperpolarization of the membrane at a blood glucose level of approximately 5 mmol/l. The injection of GLP-1 at a glycemic level <5 mmol/l does not stimulate electrical activity.

Increased levels of free fatty acids in fasted mice stimulate in vivo beta-cell electrical activity.

The electrical activity of pancreatic beta-cells in 48-h fasted mice has been recorded in vivo. Their electrical activity is exceedingly high at low levels of blood glucose when compared with control animals. For example, at a blood glucose concentration of 4.

Albumin elicits calcium signals from astrocytes in brain slices from neonatal rat cortex.

1. Albumin causes calcium signals and mitosis in cultured astrocytes, but it has not been established whether astrocytes in intact brain also respond to albumin. The effect of albumin on intracellular calcium concentration ([Ca2+]i) in single cells was therefore studied in acutely isolated cortical brain slices from the neonatal rat.

Regulation by tolbutamide and diazoxide of the electrical activity in mouse pancreatic beta-cells recorded in vivo.

1. The glucose-dependence of beta-cell electrical activity and the effects of tolbutamide and diazoxide were studied in anaesthetized mice. 2.

Oscillatory patterns of electrical activity in mouse pancreatic islets of Langerhans recorded in vivo.

Pancreatic beta-cells secrete insulin as a function of blood glucose concentration. One of the key steps in stimulus-secretion coupling is the depolarisation of the membrane and the appearance of bursts of calcium action potentials. Recently, the characteristics and glucose dependence of the oscillations in electrical activity in vivo have been described.

In vivo synchronous membrane potential oscillations in mouse pancreatic beta-cells: lack of co-ordination between islets.

1. The properties of the oscillations in electrical activity of different beta-cells within the same islet of Langerhans, and of different islets within the same pancreas, recorded in vivo, are described. 2.

The electrical activity of mouse pancreatic beta-cells recorded in vivo shows glucose-dependent oscillations.

1. The characteristics of the electrical activity of beta-cells from islets of Langerhans recorded in vivo are described. For blood glucose concentrations from 4 to 11 mM, the electrical activity of pancreatic beta-cells is oscillatory, with alternating depolarized and hyperpolarized phases.