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Biomedical subjects

Barbara Chapman

Publications and source records attributed to Barbara Chapman.

7 recordsLinked to original sources

Spontaneous retinal activity mediates development of ocular dominance columns and binocular receptive fields in v1.

The mechanisms that give rise to ocular dominance columns (ODCs) during development are controversial. Early experiments indicated a key role for retinal activity in ODC formation. However, later studies showed that in those early experiments, the retinal activity perturbation was initiated after ODCs had already formed. Moreover, recent studies concluded that early eye removals do not impact ODC segregation. Here we blocked spontaneous retinal activity during the very early stages of ODC development. This permanently disrupted the anatomical organization of ODCs and led to a dramatic increase in receptive field size for binocular cells in primary visual cortex. Our data suggest that early spontaneous retinal activity conveys crucial information about whether thalamocortical axons represent one or the other eye and that this activity mediates binocular competition important for shaping receptive fields in primary visual cortex.

Action Potentials↗

Neuronal pentraxins mediate synaptic refinement in the developing visual system.

Neuronal pentraxins (NPs) define a family of proteins that are homologous to C-reactive and acute-phase proteins in the immune system and have been hypothesized to be involved in activity-dependent synaptic plasticity. To investigate the role of NPs in vivo, we generated mice that lack one, two, or all three NPs. NP1/2 knock-out mice exhibited defects in the segregation of eye-specific retinal ganglion cell (RGC) projections to the dorsal lateral geniculate nucleus, a process that involves activity-dependent synapse formation and elimination. Retinas from mice lacking NP1 and NP2 had cholinergically driven waves of activity that occurred at a frequency similar to that of wild-type mice, but several other parameters of retinal activity were altered. RGCs cultured from these mice exhibited a significant delay in functional maturation of glutamatergic synapses. Other developmental processes, such as pathfinding of RGCs at the optic chiasm and hippocampal long-term potentiation and long-term depression, appeared normal in NP-deficient mice. These data indicate that NPs are necessary for early synaptic refinements in the mammalian retina and dorsal lateral geniculate nucleus. We speculate that NPs exert their effects through mechanisms that parallel the known role of short pentraxins outside the CNS.

Animals↗

Ephrin-As mediate targeting of eye-specific projections to the lateral geniculate nucleus.

Axon guidance cues contributing to the development of eye-specific visual projections to the lateral geniculate nucleus (LGN) have not previously been identified. Here we show that gradients of ephrin-As and their receptors (EphAs) direct retinal ganglion cell (RGC) axons from the two eyes into their stereotyped pattern of layers in the LGN. Overexpression of EphAs in ferret RGCs using in vivo electroporation induced axons from both eyes to misproject within the LGN. The effects of EphA overexpression were competition-dependent and restricted to the early postnatal period. These findings represent the first demonstration of eye-specific pathfinding mediated by axon guidance cues and, taken with other reports, indicate that ephrin-As can mediate several mapping functions within individual target structures.

Aging↗

Eye-specific retinogeniculate segregation independent of normal neuronal activity.

The segregation of initially intermingled left and right eye inputs to the dorsal lateral geniculate nucleus (DLGN) during development is thought to be in response to precise spatial and temporal patterns of spontaneous ganglion cell activity. To test this hypothesis, we disrupted the correlated activity of neighboring ganglion cells in the developing ferret retina through immunotoxin depletion of starburst amacrine cells. Despite the absence of this type of correlated activity, left and right eye inputs segregated normally in the DLGN. By contrast, when all spontaneous activity was blocked, the projections from the two eyes remained intermingled. Thus, certain features of normal neural activity patterns are not required for the formation of eye-specific projections to the DLGN.

Action Potentials↗

Receptive fields and response properties of neurons in layer 4 of ferret visual cortex.

The ferret has become a model animal for studies exploring the development of the visual system. However, little is known about the receptive-field structure and response properties of neurons in the adult visual cortex of the ferret. We performed single-unit recordings from neurons in layer 4 of adult ferret primary visual cortex to determine the receptive-field structure and visual-response properties of individual neurons. In particular, we asked what is the spatiotemporal structure of receptive fields of layer 4 neurons and what is the orientation selectivity of layer 4 neurons? Receptive fields of layer 4 neurons were mapped using a white-noise stimulus; orientation selectivity was determined using drifting, sine-wave gratings. Our results show that most neurons (84%) within layer 4 are simple cells with elongated, spatially segregated, ON and OFF subregions. These neurons are also selective for stimulus orientation; peaks in orientation-tuning curves have, on average, a half-width at half-maximum response of 21.5 +/- 1.2 degrees (mean +/- SD). The remaining neurons in layer 4 (16%) lack orientation selectivity and have center/surround receptive fields. Although the organization of geniculate inputs to layer 4 differs substantially between ferret and cat, our results demonstrate that, like in the cat, most neurons in ferret layer 4 are orientation-selective simple cells.

Animals↗

Decoupling eye-specific segregation from lamination in the lateral geniculate nucleus.

To determine whether there is a critical period for development of eye-specific layers in the lateral geniculate nucleus (LGN), we prevented the normal segregation of retinogeniculate afferents and then allowed an extended period of time for recovery. After recovery, both anatomy and physiology revealed strictly nonoverlapping territories of input from the two eyes. However, the normal stereotyped pattern of eye-specific afferent and cellular layers never developed. Instead, the eye-specific territories of afferent input emerged as variable and disorganized patches with no corresponding interlaminar spaces in the LGN. These findings reveal a critical period for coordinating the development of three processes in the LGN: the segregation of afferents from the two eyes, the spatial organization of those afferents into layers, and the alignment of postsynaptic cytoarchitecture with the afferent inputs. We also assessed the physiological consequences of preventing normal lamination and found normal single-cell responses and topographic representation of visual space in the LGN. Clusters of ON-center and OFF-center LGN cells were segregated from one another as in normal animals. However, the organization of ON and OFF sublaminas in the treated animals was disrupted.

Aging↗

No ON-OFF maps in supragranular layers of ferret visual cortex.

Primary visual cortex contains functional maps of a number of stimulus properties including ocular dominance, orientation, direction, color, and spatial frequency. These maps must be organized with respect to each other and to a single continuous retinotopic map of visual space such that each stimulus parameter is represented at each point in space. In the ferret, geniculo-cortical inputs to cortical layer IV are segregated into ON- and OFF-center patches, suggesting the possibility that there might be an additional cortical map in this species. We have used optical imaging of intrinsic signals to search for ON-OFF maps in ferret visual cortical cells and have found none. This suggests that the high degree of ON-OFF segregation seen subcortically in the ferret may play a role in the development of visual cortical receptive fields rather than in adult cortical function.

Aminobutyrates↗