Absence of local retinotopy in the mouse optic tract

Timing and Specificity of Feed-Forward Inhibition within the LGN

Visual Circuits: Mouse Retina No Longer a Level Playing Field

Rapid Plasticity of Visual Responses in the Adult Lateral Geniculate Nucleus

Anterior-Posterior Direction Opponency in the Superficial Mouse Lateral Geniculate Nucleus

Cognitive and Perceptual Functions of the Visual Thalamus

Each point in visual space is encoded at the level of the thalamus by a group of neighboring cells with overlapping receptive fields. Here we show that the receptive fields of these cells differ in size and response latency but not at random. We have found that in the cat lateral geniculate nucleus (LGN) the receptive field size and response latency of neighboring neurons are significantly correlated: the larger the receptive field, the faster the response to visual stimuli. This correlation is widespread in LGN. It is found in groups of cells belonging to the same type (e.g., Y cells), and of different types (i.e., X and Y), within a specific layer or across different layers. These results indicate that the inputs from the multiple geniculate afferents that converge onto a cortical cell (approximately 30) are likely to arrive in a sequence determined by the receptive field size of the geniculate afferents. Recent studies have shown that the peak of the spatial frequency tuning of a cortical cell shifts toward higher frequencies as the response progresses in time. Our results are consistent with the idea that these shifts in spatial frequency tuning arise from differences in the response time course of the thalamic inputs.

Active Dendritic Conductances Dynamically Regulate GABA Release from Thalamic Interneurons

Patterning events during early eye formation determine retinal cell fate and can dictate the behavior of retinal ganglion cell (RGC) axons as they navigate toward central brain targets. The temporally and spatially regulated expression of bone morphogenetic proteins (BMPs) and their receptors in the retina are thought to play a key role in this process, initiating gene expression cascades that distinguish different regions of the retina, particularly along the dorsoventral axis. Here, we examine the role of BMP and a potential downstream effector, EphB, in retinotopic map formation in the lateral geniculate nucleus (LGN) and superior colliculus (SC). RGC axon behaviors during retinotopic map formation in wild type mice are compared with those in several strains of mice with engineered defects of BMP and EphB signaling. Normal RGC axon sorting produces axon order in the optic tract that reflects the dorsoventral position of the parent RGCs in the eye. A dramatic consequence of disrupting BMP signaling is a missorting of RGC axons as they exit the optic chiasm. This sorting is not dependent on EphB. When BMP signaling in the developing eye is genetically modified, RGC order in the optic tract and targeting in the LGN and SC are correspondingly disrupted. These experiments show that BMP signaling regulates dorsoventral RGC cell fate, RGC axon behavior in the ascending optic tract and retinotopic map formation in the LGN and SC through mechanisms that are in part distinct from EphB signaling in the LGN and SC.

Functional Mechanisms Shaping Lateral Geniculate Responses to Artificial and Natural Stimuli

1. The receptive fields of collicular neurons in the cat, recorded in a single microelectrode penetration, were not centered on a point in visual space, but nested eccentrically with the smaller fields displaced toward the area centralis. The eccentric nesting was not eliminated by correcting the fields for the tangent screen distortion or by making penetrations normal to the collicular surface in coronal and parasagittal planes. These findings do not support the idea that collicular cells form topographically organized columns oriented normal to the collicular surface. 2. When the receptive fields were plotted in the visual coordinate system of the collicular map, the nesting became much more concentric, suggesting that the eccentric nesting of the receptive fields in visual space was largely a product of the retinotectal coordinate transformation. 3. The profile of a collicular receptive field, plotted in the collicular visual coordinate system is called the receptive-field image. Receptive-field images tended to have oval shapes with the long axis oriented mediolaterally. Clusters of receptive-field images, plotted for single penetrations, appeared similar wherever they occurred in the collicular map, suggesting that a common pattern of neural convergence determines the geometry of the receptive-field images in all parts of the colliculus. 4. The neural substrate of the receptive-field images was examined by tracing the theoretical patterns of neural activity which a point stimulus would produce in the retinotectal system. This analysis suggested that the shape and dimensions of the receptive-field images, and consequently the receptive fields, might be accounted for in large part by the geometry of collicular dendritic fields, the dimensions of the visual receptive fields of afferent fibers, and the retinotectal coordinate transformation. 5. Because it adjusts for the retinotectal distortion of visual space, the receptive-field image may be used to outline the distribution of collicular cells excited by a point stimulus. This makes it possible to show that a point stimulus activates large-field cells in the superficial gray layer over an area of about 2.5 by 1.5 mm in the central parts of the colliculus. It is suggested that such cells may organize the directional signals required by the oculomotor system for visual orienting behavior.

The retina and its sole output neuron, the retinal ganglion cell (RGC), comprise an excellent model in which to examine biological questions such as cell differentiation, axon guidance, retinotopic organization and synapse formation[1]. One drawback is the inability to efficiently and reliably manipulate gene expression in RGCs in vivo, especially in the otherwise accessible murine visual pathways. Transgenic mice can be used to manipulate gene expression, but this approach is often expensive, time consuming, and can produce unwanted side effects. In chick, in ovo electroporation is used to manipulate gene expression in RGCs for examining retina and RGC development. Although similar electroporation techniques have been developed in neonatal mouse pups[2], adult rats[3], and embryonic murine retinae in vitro[4], none of these strategies allow full characterization of RGC development and axon projections in vivo. To this end, we have developed two applications of electroporation, one in utero and the other ex vivo, to specifically target embryonic murine RGCs[5, 6].With in utero retinal electroporation, we can misexpress or downregulate specific genes in RGCs and follow their axon projections through the visual pathways in vivo, allowing examination of guidance decisions at intermediate targets, such as the optic chiasm, or at target regions, such as the lateral geniculate nucleus. Perturbing gene expression in a subset of RGCs in an otherwise wild-type background facilitates an understanding of gene function throughout the retinal pathway. Additionally, we have developed a companion technique for analyzing RGC axon growth in vitro. We electroporate embryonic heads ex vivo, collect and incubate the whole retina, then prepare explants from these retinae several days later. Retinal explants can be used in a variety of in vitro assays in order to examine the response of electroporated RGC axons to guidance cues or other factors. In sum, this set of techniques enhances our ability to misexpress or downregulate genes in RGCs and should greatly aid studies examining RGC development and axon projections.

The retina and its sole output neuron, the retinal ganglion cell (RGC), comprise an excellent model in which to examine biological questions such as cell differentiation, axon guidance, retinotopic organization and synapse formation[1]. One drawback is the inability to efficiently and reliably manipulate gene expression in RGCs in vivo, especially in the otherwise accessible murine visual pathways. Transgenic mice can be used to manipulate gene expression, but this approach is often expensive, time consuming, and can produce unwanted side effects. In chick, in ovo electroporation is used to manipulate gene expression in RGCs for examining retina and RGC development. Although similar electroporation techniques have been developed in neonatal mouse pups[2], adult rats[3], and embryonic murine retinae in vitro[4], none of these strategies allow full characterization of RGC development and axon projections in vivo. To this end, we have developed two applications of electroporation, one in utero and the other ex vivo, to specifically target embryonic murine RGCs[5, 6]. With in utero retinal electroporation, we can misexpress or downregulate specific genes in RGCs and follow their axon projections through the visual pathways in vivo, allowing examination of guidance decisions at intermediate targets, such as the optic chiasm, or at target regions, such as the lateral geniculate nucleus. Perturbing gene expression in a subset of RGCs in an otherwise wild-type background facilitates an understanding of gene function throughout the retinal pathway. Additionally, we have developed a companion technique for analyzing RGC axon growth in vitro. We electroporate embryonic heads ex vivo, collect and incubate the whole retina, then prepare explants from these retinae several days later. Retinal explants can be used in a variety of in vitro assays in order to examine the response of electroporated RGC axons to guidance cues or other factors. In sum, this set of techniques enhances our ability to misexpress or downregulate genes in RGCs and should greatly aid studies examining RGC development and axon projections.

Mechanisms of Neuronal Computation in Mammalian Visual Cortex

The fibre arrangement in the optic chiasma (OC) and tract (OT) was investigated with anatomical and physiological methods. In silver impregnated material, principal fibre streams can be demonstrated. In the OC, fibre bundles from each eye cross in a regular basket weave pattern, but deviations of single fibres from the predominant stream are often seen. In the OT, fibres run essentially parallel, and crossings of individual fibres are mainly restricted to the periphery of the tract, or around capillaries. Fibres in the upper segment of the OT are of thin, in the lower segments of thick diameter. Individual fibres labelled by HRP injected in the lateral geniculate body (LGB) run essentially parallel over long distances. Ventromedially to the LGB, bifurcations are found with one branch entering the LGB, the other continuing. 57% of OT-fibres had a receptive field (RF) in the contralateral, 43% in the homolateral eye; 60% in the lower, 40% in the upper visual field; and 6% had a RF in the homolateral visual field, mostly near the vertical meridian. Fibres from the central area were underrepresented in our sample. Fibres from the two eyes were mixed. The RFs of consecutively recorded fibres showed a systematic progression only exceptionally. After plotting RFs of a single penetration on a transformed isodensity ganglion cell map of the visual field, the RF's were distributed along elongated paths on this map. In the OT, such paths ran parallel or slightly inclined relative to the horizontal meridian. They were restricted to either the upper or the lower quadrant or to a path along the horizontal meridian. In the OC, the RF-paths mostly crossed the horizontal meridian at an obtuse angle (average 70 degrees). Thus, the visual field representation rotates by nearly 90 degrees from the OC to the OT. In the OC, the central area is located anteriorly, in the OT dorsally, with the upper visual quadrant laterally and the lower medially. Fibres from the two eyes were mixed and, within the range of the scatter, RFs from the homo- and contralateral eye were in register. It is concluded, that the distribution of fibres in the OC and the OT show a basic retinotopic organization superimposed by scatter.

Feedback from the visual cortex (V1) to the Lateral Geniculate Nucleus (LGN) in macaque monkey increase contrast gain of LGN neurons for black and white (B&W) and for color (C) stimuli. LGN parvocellular cells responses to B&W gratings are enhanced by feedback multiplicatively and in contrast independent manner. However, in magnocellular neurons corticofugal pathways enhance cells responses in a contrast-dependent non-linear manner. For C stimuli cortical feedback enhances parvocellular neurons responses in a very strong contrast-dependent manner. Based on these results [13] we propose a model which includes excitatory and inhibitory effects on cells activity (shunting equations) in retina and LGN while taking into account the anatomy of cortical feedback connections. The main mechanisms related to different algorithms of the data processing in the visual brain are differences in feedback properties from Vl to parvocellular (PC) and to magnocellular (MC) neurons. Descending pathways from Vl change differently receptive field (RF) structure of PC and MC cells. For B&W stimuli, in PC cells feedback changes gain similarly in the RF center and in the RF surround, leaving PC RF structure invariant. However, feedback influence MC cells in two ways: directly and through LGN interneurons, which together changes gain and sizes of their RF center differently than gain and size of the RF surround. For C stimuli PC cells operate like MC cells for B&W. The first mechanism extracts from the stimulus an important features in a independent way from other stimulus parameters, whereas the second channel changes its tuning properties as a function of other stimulus attributes like contrast and/or spatial extension. The model suggests novel idea about the possible functional role of PC and MC pathways.