Dendritic growth and remodelling of cat retinal ganglion cells during fetal and postnatal development.

We have studied the development of retinal ganglion cell morphology in the cat's visual system from early fetal to postnatal times. In particular, we have examined the contribution of growth and remodeling to the establishment of mature retinal ganglion cell form. Ganglion cells were identified by retrograde labeling with rhodamine latex microspheres deposited in the superior colliculus and lateral geniculate nucleus between embryonic day 34 (E34; birth = E65) and adulthood. To reveal the fine morphological details of retrogradely labeled ganglion cells, 48 hr later Lucifer yellow was injected intracellularly in living retinae that had been dissected and maintained in vitro. Our results show that at E35–37 the majority of ganglion cells are very simple in morphology, with a few dendritic processes that are generally aligned in a radial direction towards or away from the optic disc. During the ensuing 2 week period, there is a progressive growth and elaboration of dendrites. By E50, some ganglion cells resembling the adult alpha, beta, and gamma classes can be identified based on comparisons of the appearance and dimensions of their dendritic trees and somata with neighboring filled cells. However, ganglion cell dendrites and axons at this age express several transient morphological features. The axons of ganglion cells give rise to delicate processes originating from the intraretinal portion of the axon, including side branches, present in about half of the cells, and occasionally bifurcations that give rise to axon collaterals. These transient axonal features are present throughout development, including the neonatal period; no axon collaterals were observed after postnatal day 15, while axonal side branches persisted even at P31 but were gone by adulthood. Ganglion cell dendrites exhibit excessive branches and exuberant somatic and dendritic spines. Quantitative analysis of these processes shows that after E45 dendritic trees increase dramatically in complexity, reaching the peak number of spines and branch points by the first week of postnatal life. The number of dendritic processes then falls abruptly to reach near-adult levels by the end of the first postnatal month. Even though dendritic morphology closely resembles that seen in the adult at this age, ganglion cell bodies and dendrites must continue to grow to reach their adult siz

Visual Cells Remember Earlier Applied Target: Plasticity of Orientation Selectivity

BACKGROUND: A canonical proposition states that, in mature brain, neurons responsive to sensory stimuli are tuned to specific properties installed shortly after birth. It is amply demonstrated that that neurons in adult visual cortex of cats are orientation-selective that is they respond with the highest firing rates to preferred oriented stimuli. METHODOLOGY/PRINCIPAL FINDINGS: In anesthetized cats, prepared in a conventional fashion for single cell recordings, the present investigation shows that presenting a stimulus uninterruptedly at a non-preferred orientation for twelve minutes induces changes in orientation preference. Across all conditions orientation tuning curves were investigated using a trial by trial method. Contrary to what has been previously reported with shorter adaptation duration, twelve minutes of adaptation induces mostly attractive shifts, i.e. toward the adapter. After a recovery period allowing neurons to restore their original orientation tuning curves, we carried out a second adaptation which produced three major results: (1) more frequent attractive shifts, (2) an increase of their magnitude, and (3) an additional enhancement of responses at the new or acquired preferred orientation. Additionally, we also show that the direction of shifts depends on the duration of the adaptation: shorter adaptation in most cases produces repulsive shifts, whereas adaptation exceeding nine minutes results in attractive shifts, in the same unit. Consequently, shifts in preferred orientation depend on the duration of adaptation. CONCLUSION/SIGNIFICANCE: The supplementary response improvements indicate that neurons in area 17 keep a memory trace of the previous stimulus properties, thereby upgrading cellular performance. It also highlights the dynamic nature of basic neuronal properties in adult cortex since repeated adaptations modified both the orientation tuning selectivity and the response strength to the preferred orientation. These enhanced neuronal responses suggest that the range of neuronal plasticity available to the visual system is broader than anticipated

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

Expression of SPIG1 Reveals Development of a Retinal Ganglion Cell Subtype Projecting to the Medial Terminal Nucleus in the Mouse

Visual information is transmitted to the brain by roughly a dozen distinct types of retinal ganglion cells (RGCs) defined by a characteristic morphology, physiology, and central projections. However, our understanding about how these parallel pathways develop is still in its infancy, because few molecular markers corresponding to individual RGC types are available. Previously, we reported a secretory protein, SPIG1 (clone name; D/Bsp120I #1), preferentially expressed in the dorsal region in the developing chick retina. Here, we generated knock-in mice to visualize SPIG1-expressing cells with green fluorescent protein. We found that the mouse retina is subdivided into two distinct domains for SPIG1 expression and SPIG1 effectively marks a unique subtype of the retinal ganglion cells during the neonatal period. SPIG1-positive RGCs in the dorsotemporal domain project to the dorsal lateral geniculate nucleus (dLGN), superior colliculus, and accessory optic system (AOS). In contrast, in the remaining region, here named the pan-ventronasal domain, SPIG1-positive cells form a regular mosaic and project exclusively to the medial terminal nucleus (MTN) of the AOS that mediates the optokinetic nystagmus as early as P1. Their dendrites costratify with ON cholinergic amacrine strata in the inner plexiform layer as early as P3. These findings suggest that these SPIG1-positive cells are the ON direction selective ganglion cells (DSGCs). Moreover, the MTN-projecting cells in the pan-ventronasal domain are apparently composed of two distinct but interdependent regular mosaics depending on the presence or absence of SPIG1, indicating that they comprise two functionally distinct subtypes of the ON DSGCs. The formation of the regular mosaic appears to be commenced at the end of the prenatal stage and completed through the peak period of the cell death at P6. SPIG1 will thus serve as a useful molecular marker for future studies on the development and function of ON DSGCs

Phosphodiesterase Inhibition Increases CREB Phosphorylation and Restores Orientation Selectivity in a Model of Fetal Alcohol Spectrum Disorders

Background: Fetal alcohol spectrum disorders (FASD) are the leading cause of mental retardation in the western world and children with FASD present altered somatosensory, auditory and visual processing. There is growing evidence that some of these sensory processing problems may be related to altered cortical maps caused by impaired developmental neuronal plasticity. Methodology/Principal Findings: Here we show that the primary visual cortex of ferrets exposed to alcohol during the third trimester equivalent of human gestation have decreased CREB phosphorylation and poor orientation selectivity revealed by western blotting, optical imaging of intrinsic signals and single-unit extracellular recording techniques. Treating animals several days after the period of alcohol exposure with a phosphodiesterase type 1 inhibitor (Vinpocetine) increased CREB phosphorylation and restored orientation selectivity columns and neuronal orientation tuning. Conclusions/Significance: These findings suggest that CREB function is important for the maturation of orientation selectivity and that plasticity enhancement by vinpocetine may play a role in the treatment of sensory problems in FASD

A Reaction-Diffusion Model to Capture Disparity Selectivity in Primary Visual Cortex

Decades of experimental studies are available on disparity selective cells in visual cortex of macaque and cat. Recently, local disparity map for iso-orientation sites for near-vertical edge preference is reported in area 18 of cat visual cortex. No experiment is yet reported on complete disparity map in V1. Disparity map for layer IV in V1 can provide insight into how disparity selective complex cell receptive field is organized from simple cell subunits. Though substantial amounts of experimental data on disparity selective cells is available, no model on receptive field development of such cells or disparity map development exists in literature. We model disparity selectivity in layer IV of cat V1 using a reaction-diffusion two-eye paradigm. In this model, the wiring between LGN and cortical layer IV is determined by resource an LGN cell has for supporting connections to cortical cells and competition for target space in layer IV. While competing for target space, the same type of LGN cells, irrespective of whether it belongs to left-eye-specific or right-eye-specific LGN layer, cooperate with each other while trying to push off the other type. Our model captures realistic 2D disparity selective simple cell receptive fields, their response properties and disparity map along with orientation and ocular dominance maps. There is lack of correlation between ocular dominance and disparity selectivity at the cell population level. At the map level, disparity selectivity topography is not random but weakly clustered for similar preferred disparities. This is similar to the experimental result reported for macaque. The details of weakly clustered disparity selectivity map in V1 indicate two types of complex cell receptive field organization

Enhanced activation of NMDA receptor responses at the immature retinogeniculate synapse

The maturation of retinogeniculate excitatory transmission and intrathalamic inhibition was studied in slices of the dorsal LGN obtained from ferrets during the first 2 postnatal months. Response to optic tract stimulation at neonatal ages consisted of slow EPSPs lasting several hundred milliseconds. Application of the NMDA receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid (D-APV) during the first 2 postnatal weeks resulted in EPSPs that were reduced in peak amplitude and dramatically curtailed in duration, indicating that NMDA receptors participate strongly in retinogeniculate transmission at the immature synapse. Gradually, EPSPs became shorter in duration such that after the second postnatal week, the retinogeniculate EPSPs were only a few milliseconds in duration. At this late stage of development responses were remarkably less affected by application of D-APV. These changes in contribution of NMDA receptors to retinogeniculate transmission were found to be due to the development of strong IPSPs, the result of gradual maturation of activation of GABAergic inhibition. Indeed, application of bicuculline methiodide to block GABAA receptor- mediated IPSPs strongly enhanced the NMDA component of the EPSPs in more mature cells. The voltage dependence and kinetics of NMDA-induced excitatory postsynaptic currents (NMDA EPSCs) were characterized by voltage-clamp recordings after blocking AMPA/kainate receptors with 6- cyano-7-nitroquinoxaline-2,3-dione and GABAA receptors wit' bicuculline methiodide. The voltage dependence of the NMDA EPSCs remained unaltered with age. During the first postnatal month the kinetic properties of the NMDA EPSCs also remained unaltered, but a reduction in EPSC duration was observed within the following weeks, well after the critical period of anatomical reorganization.(ABSTRACT TRUNCATED AT 250 WORDS)</jats:p