During vision, it is believed that neural activity in the primary visual cortex is predominantly driven by sensory input from the environment. However, visual cortical neurons respond to repeated presentations of the same stimulus with a high degree of variability. Although this variability has been considered to be noise owing to random spontaneous activity within the cortex, recent studies show that spontaneous activity has a highly coherent spatio-temporal structure. This raises the possibility that the pattern of this spontaneous activity may shape neural responses during natural viewing conditions to a larger extent than previously thought. Here, we examine the relationship between spontaneous activity and the response of primary visual cortical neurons to dynamic natural-scene and random-noise film images in awake, freely viewing ferrets from the time of eye opening to maturity. The correspondence between evoked neural activity and the structure of the input signal was weak in young animals, but systematically improved with age. This improvement was linked to a shift in the dynamics of spontaneous activity. At all ages including the mature animal, correlations in spontaneous neural firing were only slightly modified by visual stimulation, irrespective of the sensory input. These results suggest that in both the developing and mature visual cortex, sensory evoked neural activity represents the modulation and triggering of ongoing circuit dynamics by input signals, rather than directly reflecting the structure of the input signal itself.

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.

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.

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.

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.

Natural scene coding in ferret visual cortex was investigated using a new technique for multi-site recording of neuronal activity from the cortical surface. Surface recordings accurately reflected radially aligned layer 2/3 activity. At individual sites, evoked activity to natural scenes was weakly correlated with the local image contrast structure falling within the cells' classical receptive field. However, a population code, derived from activity integrated across cortical sites having retinotopically overlapping receptive fields, correlated strongly with the local image contrast structure. Cell responses demonstrated high lifetime sparseness, population sparseness, and high dispersal values, implying efficient neural coding in terms of information processing. These results indicate that while cells at an individual cortical site do not provide a reliable estimate of the local contrast structure in natural scenes, cell activity integrated across distributed cortical sites is closely related to this structure in the form of a sparse and dispersed code.

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.

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.