Firing pattern of O-LM cells in mouse hippocampal CA1

This data set includes the raw data files from some experimental O-LM cells featured in Quattrocolo and Maccaferri (2013) that were later used to constrain the model cells of the model CA1 neural network published in: Marianne J. Bezaire, Ivan Raikov, Kelly Burk, Dhrumil Vyas, and Ivan Soltesz. Interneuronal mechanisms of hippocampal theta oscillations in full-scale models of the CA1 circuit. eLife, 2016. Results from the experiments are described in: Giulia Quattrocolo and Gianmaria Maccaferri. Novel GABAergic circuits mediating excitation/inhibition of Cajal-Retzius cells in the developing hippocampus. The Journal of Neuroscience, 33(13):5486–5498, 2013. doi: 10.1523/JNEUROSCI.5680-12.201

Heterotopic Transplantations Reveal Environmental Influences on Interneuron Diversity and Maturation

During embryogenesis, neural progenitors in the ganglionic eminences give rise to diverse GABAergic interneuron subtypes that populate all forebrain regions. The extent to which these cells are genetically predefined or determined by postmigratory environmental cues remains unknown. To address this question, we performed homo- and heterotopic transplantation of early postnatal MGE-derived cortical and hippocampal interneurons. Grafted cells migrated, and displayed neurochemical, electrophysiological, morphological, and neurochemical profiles similar to endogenous interneurons. Our results indicate that the host environment regulates the proportion of interneuron classes in the brain region. However, some specific interneuron subtypes retain characteristics representative of their donor brain regions

Distinct developmental patterns in the expression of transient, persistent, and resurgent Na+ currents in entorhinal cortex layer-II neurons

Sub- and near-threshold voltage-dependent Na+ currents (VDSCs) are of major importance in determining the electrical properties of medial entorhinal cortex (mEC) layer-II neurons. Developmental changes in the ability of mEC layer-II stellate cells (SCs) to generate Na+-dependent, subthreshold electrical events have been reported between P14 and P18. In this study we examined the modifications occurring in the various components of VDSCs during postnatal development of mEC SCs. The transient, resurgent, and persistent Na+ currents (I-NaT, I-NaR and I-Nap, respectively) showed distinct patterns of developmental expression in the time window considered (PS to P24-27). All three currents prominently and steeply increased in absolute amplitude and conductance from P5 to at least P16. However, capacitive charge accumulation, an index of membrane surface area, also markedly increased in the same time window, and in the case of I-NaT the specific conductance per unit of accumulated capacitive charge remained relatively constant. By contrast, specific I-NaR and I-Nap conductances showed a significant tendency to increase, especially from P5 to P18. Neither I-NaR nor I-Nap represented a constant fraction of the total Na+ current at all developmental ages. Indeed, detectable levels of I-NaR and I-Nap were present in only similar to 20% and similar to 70%, respectively, of the cells on P5, and were observed in all cells only from P10 onwards. Moreover, the average I-NaR-to-I-NaT conductance ratio increased steadily from similar to 0.004 (P5) up to a plateau level of similar to 0.05 (P22+), whereas the I-Nap-to-I-NaT conductance ratio increased only from similar to 0.009 on P5 to similar to 0.02 on P22+. The relative increase in conductance ratio from P5 to P22 was significantly greater for I-NaR than for I-Nap, indicating that I-NaR expression starts later than that of I-Nap. These findings show that in mEC layer-II SCs the single functional components of the VDSC are regulated differentially from each other as far as their developmental expression is concerned

Generation of an enhancer-driven gene expression viral tool specific to dentate granule cell-types through direct hippocampal injection

Accurate investigations of neural circuitry require specific genetic access to individual circuit elements, i.e., the myriad neuronal cell-types in the brain. However, native promoters cannot achieve this because while most genes are expressed in the brain, few are expressed in a single neuronal cell-type. We recently used enhancers, the subcomponents of the transcriptional apparatus which tell promoters when and where to express, combined with heterologous minimal promoters to increase specificity of transgene expression, an approach we call Enhancer-Driven Gene Expression (EDGE). As we discuss, EDGE is a marked improvement in specificity over native promoters, but still requires careful anatomical analysis to avoid off-target effects. In this study we present a more complete set of genomic markers from the mouse brain and characterize a novel EDGE viral vector capable of specifically driving expression in distinct subtypes of hippocampal neurons, even though it can express in other cell-types elsewhere. The advent of cell-type specific viral tools in wild-type animals provides a powerful strategy for neural circuit investigation and holds promise for studies using animal models for which transgenic tools are not available

Prenatal development of the human entorhinal cortex

Little is known about the development of the human entorhinal cortex (EC), a major hub in a widespread network for learning and memory, spatial navigation, high-order processing of object information, multimodal integration, attention and awareness, emotion, motivation, and perception of time. We analyzed a series of 20 fetal and two adult human brains using Nissl stain, acetylcholinesterase (AChE) histochemistry, and immunocytochemistry for myelin basic protein (MBP), neuronal nuclei antigen (NeuN), a pan-axonal neurofilament marker, and synaptophysin, as well as postmortem 3T MRI. In comparison with other parts of the cerebral cortex, the cytoarchitectural differentiation of the EC begins remarkably early, in the 10th week of gestation (w.g.). The differentiation occurs in a superficial magnocellular layer in the deep part of the marginal zone, accompanied by cortical plate (CP) condensation and multilayering of the deep part of CP. These processes last until the 13-14th w.g. At 14 w.g., the superficial lamina dissecans (LD) is visible, which divides the CP into the lamina principalis externa (LPE) and interna (LPI). Simultaneously, the rostral LPE separates into vertical cell-dense islands, whereas in the LPI, the deep LD emerges as a clear acellular layer. In the 16th w.g., the LPE remodels into vertical cell-dense and cell-sparse zones with a caudorostral gradient. At 20 w.g., NeuN immunoreactivity is most pronounced in the islands of layer II cells, whereas migration and differentiation inside-out gradients are seen simultaneously in both the upper (LPE) and the lower (LPI) pyramidal layers. At this stage, the EC adopts for the first time an adult-like cytoarchitectural organization, the superficial LD becomes discernible by 3T MRI, MBP-expressing oligodendrocytes first appear in the fimbria and the perforant path (PP) penetrates the subiculum to reach its molecular layer and travels along through the Cornu Ammonis fields to reach the suprapyramidal blade of the dentate gyrus, whereas the entorhinal-dentate branch perforates the hippocampal sulcus about 2-3 weeks later. The first AChE reactivity appears as longitudinal stripes at 23 w.g. in layers I and II of the rostrolateral EC and then also as AChE-positive in-growing fibers in islands of superficial layer III and layer II neurons. At 40 w.g., myelination of the PP starts as patchy MBP-immunoreactive oligodendrocytes and their processes. Our results refute the possibility of an inside-out pattern of the EC development and support the key role of layer II prospective stellate cells in the EC lamination. As the early cytoarchitectural differentiation of the EC is paralleled by the neurochemical development, these developmental milestones in EC structure and connectivity have implications for understanding its normal function, including its puzzling modular organization and potential contribution to consciousness content (awareness), as well as for its insufficiently explored deficits in developmental, psychiatric, and degenerative brain disorders