Neurons in the cerebral cortex are organized into anatomical columns, with ensembles of cells arranged from the surface to the whitematter.Withinacolumn,neuronsoftensharefunctionalproperties,suchasselectivityforstimulusorientation;columnswith distinctproperties,suchasdifferentpreferredorientations,tilethecorticalsurfaceinorderlypatterns.Thisfunctionalarchitecture was discovered with the relatively sparse sampling of microelectrode recordings. Optical imaging of membrane voltage or metabolic activity elucidated the overall geometry of functional maps, but is averaged over many cells (resolution >100mm). Consequently, the purity of functional domains and the precision of the borders between them could not be resolved. Here, we labelled thousands of neurons of the visual cortex with a calcium-sensitive indicator in vivo. We then imaged the activity of neuronal populations at single-cell resolution with two-photon microscopy up to a depth of 400mm. In rat primary visual cortex, neurons had robust orientation selectivity but there was no discernible local structure; neighbouring neurons often responded to different orientations. In area 18 of cat visual cortex, functional maps were organized at a fine scale. Neurons with opposite preferences for stimulus direction were segregated with extraordinary spatial precision in three dimensions, with columnar borders one to two cells wide. These results indicate that cortical maps can be built with single-cell precision.

/pdf/functional-imaging-with-cellular-resolution-reveals-precise-1ja68x3iun.pdf

Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex

Genetic methods available in mice are likely to be powerful tools in dissecting cortical circuits. However, the visual cortex, in which sensory coding has been most thoroughly studied in other species, has essentially been neglected in mice perhaps because of their poor spatial acuity and the lack of columnar organization such as orientation maps. We have now applied quantitative methods to characterize visual receptive fields in mouse primary visual cortex V1 by making extracellular recordings with silicon electrode arrays in anesthetized mice. We used current source density analysis to determine laminar location and spike waveforms to discriminate putative excitatory and inhibitory units. We find that, although the spatial scale of mouse receptive fields is up to one or two orders of magnitude larger, neurons show selectivity for stimulus parameters such as orientation and spatial frequency that is near to that found in other species. Furthermore, typical response properties such as linear versus nonlinear spatial summation (i.e., simple and complex cells) and contrast-invariant tuning are also present in mouse V1 and correlate with laminar position and cell type. Interestingly, we find that putative inhibitory neurons generally have less selective, and nonlinear, responses. This quantitative description of receptive field properties should facilitate the use of mouse visual cortex as a system to address longstanding questions of visual neuroscience and cortical processing.

https://www.jneurosci.org/content/jneuro/28/30/7520.full.pdf

Highly Selective Receptive Fields in Mouse Visual Cortex

The ability to follow arbitrary associations, such as “stop at red”, is integral to everyday behaviour and the primate brain is quick to learn them. Both the prefrontal complex and the striatum have been implicated in this process, but their respective roles are largely unknown. An experiment in which brain activity in these two areas was recorded while monkeys learned new associations shows that the learning-related changes occur much more quickly in the striatum, but that changes in the prefrontal cortex were more closely related to improved performance of the new task. It is possible that the striatum learns first, then ‘trains’ the prefrontal cortex. To navigate our complex world, our brains have evolved a sophisticated ability to quickly learn arbitrary rules such as ‘stop at red’. Studies in monkeys using a laboratory test of this capacity—conditional association learning—have revealed that frontal lobe structures (including the prefrontal cortex) as well as subcortical nuclei of the basal ganglia are involved in such learning1,2,3,4,5. Neural correlates of associative learning have been observed in both brain regions6,7,8,9,10,11,12,13,14, but whether or not these regions have unique functions is unclear, as they have typically been studied separately using different tasks. Here we show that during associative learning in monkeys, neural activity in these areas changes at different rates: the striatum (an input structure of the basal ganglia) showed rapid, almost bistable, changes compared with a slower trend in the prefrontal cortex that was more in accordance with slow improvements in behavioural performance. Also, pre-saccadic activity began progressively earlier in the striatum but not in the prefrontal cortex as learning took place. These results support the hypothesis that rewarded associations are first identified by the basal ganglia, the output of which ‘trains’ slower learning mechanisms in the frontal cortex15.

Different time courses of learning-related activity in the prefrontal cortex and striatum

The specificity of cortical neuron connections creates columns of functionally similar neurons spanning from the pia to the white matter. Here we investigate whether there is an additional, finer level of specificity that creates subnetworks of excitatory neurons within functional columns. We tested for fine-scale specificity of connections to cortical layer 2/3 pyramidal neurons in rat visual cortex by using cross-correlation analyses of synaptic currents evoked by photostimulation. Recording simultaneously from adjacent layer 2/3 pyramidal cells, we find that when they are connected to each other (20% of all recorded pairs) they share common input from layer 4 and within layer 2/3. When adjacent layer 2/3 neurons are not connected to each other, they share very little (if any) common excitatory input from layers 4 and 2/3. In contrast, all layer 2/3 neurons share common excitatory input from layer 5 and inhibitory input from layers 2/3 and 4, regardless of whether they are connected to each other. Thus, excitatory connections from layer 4 to layer 2/3 and within layer 2/3 form fine-scale assemblies of selectively interconnected neurons; inhibitory connections and excitatory connections from layer 5 link neurons across these fine-scale subnetworks. Relatively independent subnetworks of excitatory neurons are therefore embedded within the larger-scale functional architecture; this allows neighbouring neurons to convey information more independently than suggested by previous descriptions of cortical circuitry.

Excitatory cortical neurons form fine-scale functional networks

Broadly Tuned Response Properties of Diverse Inhibitory Neuron Subtypes in Mouse Visual Cortex

The rat is used widely to study various aspects of vision including developmental events and numerous pathologies, but surprisingly little is known about the functional properties of single neurons...

Receptive field properties of single neurons in rat primary visual cortex.

Transplantation of olfactory ensheathing cells into spinal cord lesions promotes regeneration of cut axons into terminal fields and functional recovery. This repair involves the formation of a peripheral nerve-like bridge in which perineurial-like fibroblasts are organized into a longitudinal stack of parallel tubular channels, some of which contain regenerating axons enwrapped by Schwann-like olfactory ensheathing cells. The present study examines whether cut retinal ganglion cell axons will also respond to these cells, and if so, whether they form the same type of arrangement. In adult rats, the optic nerve was completely severed behind the optic disc, and a matrix containing cultured olfactory ensheathing cells was inserted between the proximal and distal stumps. After 6 months, the transplanted cells had migrated for up to 10 mm into the distal stump. Anterograde labeling with cholera toxin B showed that cut retinal ganglion cell axons had regenerated through the transplants, entered the distal stump, and elongated for 10 mm together with the transplanted cells. Electron microscopy showed that a peripheral nerve-like tissue had been formed, similar to that seen in the spinal cord transplants. However, in contrast to the spinal cord, the axons did not reach the terminal fields, but terminated in large vesicle-filled expansions beyond which the distal optic nerve stump was reduced to a densely interwoven mass of astrocytic processes.

https://www.jneurosci.org/content/jneuro/23/21/7783.full.pdf

Transplanted Olfactory Ensheathing Cells Promote Regeneration of Cut Adult Rat Optic Nerve Axons

METHODS. Purified neonatal Schwann cells derived from congenic rats were grafted into the subretinal space of 3- to 4-week-old dystrophic RCS rats. Graft placement was confirmed using Schwann cells labeled in vitro with the fluorescent dye Hoechst 33342 or in grafted eyes processed for electron microscopy (48-hour to 1-month survival). At longer intervals, up to 9 months after surgery, animals were examined for photoreceptor survival; preservation of a visual reflex, headtracking to moving stripes; and preservation of visual receptive fields associated with the region of graft placement. RESULTS. One week after the graft was performed, Schwann cells had integrated into the subretinal space with little evidence of a reactive response. When screened for head-tracking to moving stripes, Schwann cell‐ grafted animals performed better than sham-treated or control dystrophic animals. Threshold sensitivity measurements and visual field assessment made by recording from the superior colliculus also showed a significant level of preserved function compared with control animals. Functional rescue was correlated with photoreceptor survival and could be observed for at least 9 months after grafting. CONCLUSIONS. Schwann cells injected into the subretinal space limit functional deterioration and prolong photoreceptor survival. It is suggested that they act by local release of growth factors that either support photoreceptors directly and/or stimulate phagocytosis in RPE cells. (Invest Ophthalmol Vis Sci. 2000;41:518 ‐528)

https://espace.library.uq.edu.au/view/UQ:269193/UQ269193_OA.pdf

Yves Sauvé

Papers

Receptive field properties of single neurons in rat primary visual cortex.

Transplanted Olfactory Ensheathing Cells Promote Regeneration of Cut Adult Rat Optic Nerve Axons

Schwann cell grafting into the retina of the dystrophic RCS rat limits functional deterioration