Non-Centered Spike-Triggered Covariance Analysis Reveals Neurotrophin-3 as a Developmental Regulator of Receptive Field Properties of ON-OFF Retinal Ganglion Cells

The functional separation of ON and OFF pathways, one of the fundamental features of the visual system, starts in the retina. During postnatal development, some retinal ganglion cells (RGCs) whose dendrites arborize in both ON and OFF sublaminae of the inner plexiform layer transform into RGCs with dendrites that monostratify in either the ON or OFF sublamina, acquiring final dendritic morphology in a subtype-dependent manner. Little is known about how the receptive field (RF) properties of ON, OFF, and ON-OFF RGCs mature during this time because of the lack of a reliable and efficient method to classify RGCs into these subtypes. To address this deficiency, we developed an innovative variant of Spike Triggered Covariance (STC) analysis, which we term Spike Triggered Covariance – Non-Centered (STC-NC) analysis. Using a multi-electrode array (MEA), we recorded the responses of a large population of mouse RGCs to a Gaussian white noise stimulus. As expected, the Spike-Triggered Average (STA) fails to identify responses driven by symmetric static nonlinearities such as those that underlie ON-OFF center RGC behavior. The STC-NC technique, in contrast, provides an efficient means to identify ON-OFF responses and quantify their RF center sizes accurately. Using this new tool, we find that RGCs gradually develop sensitivity to focal stimulation after eye opening, that the percentage of ON-OFF center cells decreases with age, and that RF centers of ON and ON-OFF cells become smaller. Importantly, we demonstrate for the first time that neurotrophin-3 (NT-3) regulates the development of physiological properties of ON-OFF center RGCs. Overexpression of NT-3 leads to the precocious maturation of RGC responsiveness and accelerates the developmental decrease of RF center size in ON-OFF cells. In summary, our study introduces STC-NC analysis which successfully identifies subtype RGCs and demonstrates how RF development relates to a neurotrophic driver in the retina

Pan-retinal characterisation of Light Responses from Ganglion Cells in the Developing Mouse Retina

International audienceWe have investigated the ontogeny of light-driven responses in mouse retinal ganglion cells (RGCs). Using a large-scale, high-density multielectrode array, we recorded from hundreds to thousands of RGCs simultaneously at pan-retinal level, including dorsal and ventral locations. Responses to di erent contrasts not only revealed a complex developmental pro le for ON, OFF and ON-OFF responses, but also unveiled di erences between dorsal and ventral RGC responses. At eye-opening, dorsal RGCs of all types were more responsive to light, perhaps indicating an environmental priority to nest viewing for pre-weaning pups. The developmental pro le of ON and OFF responses exhibited antagonistic behaviour, with the strongest ON responses shortly after eye-opening, followed by an increase in the strength of OFF responses later on. Further, we found that with maturation receptive eld (RF) center sizes decrease, spike-triggered averaged responses to white noise become stronger, and centers become more circular while maintaining di erences between RGC types. We conclude that the maturation of retinal functionality is not spatially homogeneous, likely re ecting ecological requirements that favour earlier maturation of the dorsal retina

Postnatal development of GABAergic signalling in the rat lateral geniculate nucleus: presynaptic dendritic mechanisms

Diverse forms of GABAergic inhibition are found in the mature brain. To understand how this diversity develops, we studied the changes in morphology of inhibitory interneurons and changes in interneuron-mediated synaptic transmission in the rat dorsal lateral geniculate nucleus (dLGN). We found a steady expansion of the dendritic tree of interneurons over the first three postnatal weeks. During this period, the area around a thalamocortical cell from which GABAA inhibition could be elicited also expanded. Dendritic branching and burst firing in interneurons evolved more slowly. The distal dendrites of interneurons began to branch extensively after the third week, and at the same time burst firing appeared. The appearance of burst firing and an elaborated dendritic tree were accompanied by a pronounced GABAB inhibition of thalamocortical cells. Thus, GABA inhibition of thalamocortical cells developed from one type of GABAA inhibition (spatially restricted) in the young animal into two distinct types of GABAA inhibition (short- and long-range) and GABAB inhibition in the adult animal. The close temporal relationships between the development of the diverse forms of inhibition and the postnatal changes in morphology of local GABAergic interneurons in the dLGN suggest that postnatal dendritic maturation is an important presynaptic factor for the developmental time course of the various types of feedforward inhibition in thalamus

Prostaglandins regulate nuclear localization of Fascin and its function in nucleolar architecture

Fascin, a highly conserved actin-bundling protein, localizes and functions at new cellular sites in both Drosophila and multiple mammalian cell types. During Drosophila follicle development, in addition to being cytoplasmic, Fascin is in the nuclei of the germline-derived nurse cells during stages 10B–12 (S10B–12) and at the nuclear periphery during stage 13 (S13). This localization is specific to Fascin, as other actin-binding proteins, Villin and Profilin, do not exhibit the same subcellular distribution. In addition, localization of fascin1 to the nucleus and nuclear periphery is observed in multiple mammalian cell types. Thus the regulation and function of Fascin at these new cellular locations is likely to be highly conserved. In Drosophila, loss of prostaglandin signaling causes a global reduction in nuclear Fascin and a failure to relocalize to the nuclear periphery. Alterations in nuclear Fascin levels result in defects in nucleolar morphology in both Drosophila follicles and cultured mammalian cells, suggesting that nuclear Fascin plays an important role in nucleolar architecture. Given the numerous roles of Fascin in development and disease, including cancer, our novel finding that Fascin has functions within the nucleus sheds new light on the potential roles of Fascin in these contexts

Motivation and Overview of Hydrological Ensemble Post-processing

In this introduction to this chapter on hydrologic post-processing, we discuss the different but complementary directives that the “art” of post-processing must satisfy: the particular directive defined by specific applications and user needs; versus the general directive of making any ensemble member indistinguishable from the observations. Also discussed are the features of hydrologic post-processing that are similar and separate from meteorological post-processing, providing a tie-in to early chapters in this handbook. We also provide an overview of the different aspects the practitioner should keep in mind when developing and implementing algorithms to adequately “correct and calibrate” ensemble forecasts: when forecast uncertainties should be characterized separately versus maintaining a “lumped” approach; additional aspects of hydrological ensembles that need to be maintained to satisfy additional user requirements, such as temporal covariability in the ensemble time series, an overview of the different post-processing approaches being used in practice and in the literature, and concluding with a brief overview of more specific requirements and challenges implicit in the “art” of post-processing