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M Weliky

Publications and source records attributed to M Weliky.

12 recordsLinked to original sources

Spontaneous activity in developing ferret visual cortex in vivo.

Multi-electrode extracellular recordings in area 17 of awake behaving ferrets were conducted to characterize the pattern of spontaneous activity in the developing visual cortex before eye opening. A linear array of 16 microwire electrodes was used to record extracellular neuronal activity across a 3.2 mm strip of visual cortex between postnatal days 22 and 28. Whereas synchronous bursts of activity were observed at all recording sites, cross-correlation analysis revealed that the timing of spike activity at all electrodes was not precisely correlated. Correlated activity between cortical sites exhibited a patchy organization having long-range components. Long-range correlated activity was observed between cortical patches that were separated by a mean distance of 1 mm. The spatial pattern of correlated activity persisted during transient lateral geniculate nucleus (LGN) activity block, indicating that long-range correlated activity is generated by intrinsic circuits within the cortex, independent of LGN input activity. These results demonstrate an innate patchy organization of correlated spontaneous activity within the cortex during the early development of cortical functional and anatomical organization.

Action Potentials↗

Correlational structure of spontaneous neuronal activity in the developing lateral geniculate nucleus in vivo.

The properties of spontaneous activity in the developing visual pathway beyond the retina are unknown. Multielectrode recordings in the lateral geniculate nucleus (LGN) of awake behaving ferrets, before eye opening, revealed patterns of spontaneous activity that reflect a reshaping of retinal drive within higher visual stages. Significant binocular correlations were present only when cortico-thalamic feedback was intact. In the absence of retinal drive, cortico-thalamic feedback was required to sustain correlated LGN bursting. Activity originating from the contralateral eye drove thalamic activity far more strongly than that originating from the ipsilateral eye. Thus, in vivo patterns of LGN spontaneous activity emerge from interactions between retina, thalamus, and cortex.

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Recording and manipulating the in vivo correlational structure of neuronal activity during visual cortical development.

Many aspects of visual cortical functional architecture, such as orientation and ocular dominance columns, are present before animals have had any visual experience, indicating that the initial formation of cortical circuitry takes place without the influence of environmental cues. For this reason, it has been proposed that spontaneous activity within the developing visual pathway carries instructive information to guide the early establishment of cortical circuits. Recently developed recording and stimulation techniques are revealing new information about the in vivo organization of this spontaneous activity and its contribution to cortical development. Multielectrode recordings in the developing lateral geniculate nucleus (LGN) of ferrets demonstrate that retinal spontaneous activity is not simply relayed to the visual cortex, but is reshaped and transformed by a variety of mechanisms including cortical feedback and endogenous oscillatory activity. The resulting patterns are consistent with many of the predictions of correlation-based models of cortical development. In addition, the introduction of artificially correlated activity into the visual pathway disrupts some but not all aspects of orientation tuning development. Thus, while these results support an instructive role of spontaneous activity in shaping cortical development, there still appears to be a number of aspects of this process that cannot be accounted for by activity alone.

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Disruption of orientation tuning in visual cortex by artificially correlated neuronal activity.

In the primary visual cortex, the development of orientation selectivity is influenced by patterns of neural activity. The introduction of artificially correlated activity into the visual pathway (through synchronous activation of retinal ganglion cell axons in the optic nerve) substantially weakens the orientation selectivity of neurons in superficial and deep cortical layers. This is consistent with activity having an instructive role in shaping cortical neuron receptive field tuning properties.

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Relationships between local synaptic connections and orientation domains in primary visual cortex.

Combined optical imaging of ferret primary visual cortex in vivo and scanning laser photostimulation in brain slices were used to determine the spatial relationships between synaptic inputs onto individual neurons and the pattern of orientation columns. In the upper cortical layers, both excitatory and inhibitory inputs originated primarily from regions with orientation tuning similar to that of the recorded neurons; the shapes of the input tuning curves were indistinguishable. The orientation distributions of both types of inputs centered around the orientation of the recorded neurons, and no evidence for preferential cross-orientation inputs, either excitatory or inhibitory, was observed. These patterns of synaptic connectivity are most consistent with feedforward models for generation of orientation selectivity and are inconsistent with the patterns required by models based on cross-orientation inhibition.

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A systematic map of direction preference in primary visual cortex.

Neurons in the primary visual cortex respond selectively to the orientation of edges and their direction of motion. Orientation preference is mapped in a systematic fashion across the cortical surface, such that neurons in adjacent columns have similar but slightly shifted preferred orientations. Microelectrode studies have suggested that direction preference is also arranged in a systematic fashion, but exactly how this response property is mapped remains unclear. Here we show by optical imaging of intrinsic signals in ferret cortical area 17 that there is a mosaic-like map of direction preference. This map consists of numerous regions within which direction preference changes in a slow, continuous fashion. These regions are separated by winding boundaries (fractures) across which direction preference shifts abruptly, often by 180 degrees. Comparison of direction and orientation preference maps shows that these fractures subdivide iso-orientation domains into regions selective for opposite directions of motion.

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Patterns of excitation and inhibition evoked by horizontal connections in visual cortex share a common relationship to orientation columns.

Combined optical imaging and electrophysiological techniques were used to assess directly the functional nature of long-range excitatory and inhibitory synaptic interactions between orientation columns in area 17 of ferret visual cortex. A significant correlation was found between the layout of iso-orientation columns and the pattern of evoked synaptic inputs between cortical sites: the largest-amplitude inhibitory and excitatory synaptic responses were evoked in single neurons when stimulation and recording electrodes were located in orientation columns sharing the same angle preference. Both excitatory and inhibitory synaptic responses decreased in amplitude when stimulation and recording electrodes were located in orientation columns with orthogonal angle preferences. Changing the stimulus intensity altered the balance of evoked excitation and inhibition without changing the columnar specificity of inputs. These results directly demonstrate that horizontal connections modulate both excitatory and inhibitory synaptic interactions between iso-orientation columns.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Functional mapping of horizontal connections in developing ferret visual cortex: experiments and modeling.

In cat striate cortex, patchy horizontal axonal projections link columns of similar orientation specificity. To assess the physiological correlates of such clustered projections, a new multisite stimulation technique was used to functionally map the pattern of horizontal synaptic inputs onto single layer 2/3 cells within tangential slices of developing ferret visual cortex. Twenty-four separate sets of horizontal fibers were stimulated within a 1200 microns strip of cortex, while evoked synaptic responses were recorded using whole-cell patch methods. For most cells, input maps demonstrated the presence of clustered horizontal connections in which multiple strong and weak synaptic responses were alternately evoked across the stimulated cortical region. Recordings from up to nine cells in a single slice revealed that patterns of synaptic input were closely correlated for cells in close proximity, and that this correlation decreased with distance, with no correlation at distances greater than 500 microns. To determine whether these physiological results were consistent with the known anatomical linkage of iso-orientation columns by clustered horizontal connections, mathematical analysis and computer simulations were performed upon orientation tuning maps obtained from optical imaging of activity-dependent intrinsic signals in mature ferret visual cortex. Optical imaging revealed an organization of iso-orientation domains consisting of broad regions of cortex across which orientation preference smoothly varied, together with "orientation centers" around which orientation preference was arranged in a pinwheel manner. The distribution of synaptic connections between different cortical sites was simulated by a model of functionally linked iso- orientation columns. Simulated synaptic input maps, generated by the same stimulation and recording arrangements used in our experimental protocol, accurately reproduced the observed patterns of clustered inputs onto experimentally recorded cells. These results indicate that even at the time of eye opening, prior to extensive visual experience, most cells receive patterns of synaptic inputs consistent with a clustered organization of horizontal connections that functionally link iso-orientation columns.

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Notochord morphogenesis in Xenopus laevis: simulation of cell behavior underlying tissue convergence and extension.

Cell intercalation and cell shape changes drive notochord morphogenesis in the African frog, Xenopus laevis. Experimental observations show that cells elongate mediolaterally and intercalate between one another, causing the notochord to lengthen and narrow. Descriptive observations provide few clues as to the mechanisms that coordinate and drive these cell movements. It is possible that a few rules governing cell behavior could orchestrate the shaping of the entire tissue. We test this hypothesis by constructing a computer model of the tissue to investigate how rules governing cell motility and cell-cell interactions can account for the major features of notochord morphogenesis. These rules are drawn from the literature on in vitro cell studies and experimental observations of notochord cell behavior. The following types of motility rules are investigated: (1) refractory tissue boundaries that inhibit cell motility, (2) statistical persistence of motion, (3) contact inhibition of protrusion between cells, and (4) polarized and nonpolarized protrusive activity. We show that only the combination of refractory boundaries, contact inhibition and polarized protrusive activity reproduces normal notochord development. Guided by these rules, cells spontaneously align into a parallel array of elongating cells. Self alignment optimizes the geometric conditions for polarized protrusive activity by progressively minimizing contact inhibition between cells. Cell polarization, initiated at refractory tissue boundaries, spreads along successive cell rows into the tissue interior as cells restrict and constrain their neighbors' directional bias. The model demonstrates that several experimentally observed intrinsic cell behaviors, operating simultaneously, may underlie the generation of coordinated cell movements within the developing notochord.

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The mechanical basis of cell rearrangement. I. Epithelial morphogenesis during Fundulus epiboly.

Many morphogenetic processes are accomplished by coordinated cell rearrangements. These rearrangements are accompanied by substantial shifts in the neighbor relationships between cells. Here we propose a model for studying morphogenesis in epithelial sheets by directed cell neighbor change. Our model describes cell rearrangements by accounting for the balance of forces between neighboring cells within an epithelium. Cell rearrangement and cell shape changes occur when these forces are not in mechanical equilibrium. We will show that cell rearrangement within the epidermal enveloping layer (EVL) of the teleost fish Fundulus during epiboly can be explained solely in terms of the balance of forces generated among constituent epithelial cells. Within a cell, we account for circumferential elastic forces and the force generated by hydrostatic and osmotic pressure. The model treats epithelial cells as two-dimensional polygons where the mechanical forces are applied to the polygonal nodes. A cell node protrudes or contracts when the nodal forces are not in mechanical equilibrium. In an epithelial sheet, adjacent cells share common boundary nodes; in this way, mechanical force is transmitted from cell to cell, mimicking junctional coupling. These junctional nodes can slide, and nodes may appear or disappear, so that the number of polygonal sides is variable. Computer graphics allows us to compare numerical simulations of the model with time-lapse cinemicroscopy of cell rearrangements in the living embryo, and data obtained from fixed and silver stained embryos. By manipulating the mechanical properties of the model cells we can study the conditions necessary to reproduce normal cell behavior during Fundulus epiboly. We find that simple stress relaxation is sufficient to account for cell rearrangements among interior cells of the EVL when they are isotropically contractile. Experimental observations show that the number of EVL marginal cells continuously decreases throughout epiboly. In order for the simulation to reproduce this behavior, cells at the EVL boundary must generate protrusive forces rather than contractile tension forces. Therefore, the simulation results suggest that the mechanical properties of EVL marginal cells at their leading edge must be quite different from EVL interior cells.

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