Vision drives correlated activity without patterned spontaneous activity in developing Xenopus retina

Developing amphibians need vision to avoid predators and locate food before visual system circuits fully mature. Xenopus tadpoles can respond to visual stimuli as soon as retinal ganglion cells (RGCs) innervate the brain, however, in mammals, chicks and turtles, RGCs reach their central targets many days, or even weeks, before their retinas are capable of vision. In the absence of vision, activity-dependent refinement in these amniote species is mediated by waves of spontaneous activity that periodically spread across the retina, correlating the firing of action potentials in neighboring RGCs. Theory suggests that retinorecipient neurons in the brain use patterned RGC activity to sharpen the retinotopy first established by genetic cues. We find that in both wild type and albino Xenopus tadpoles, RGCs are spontaneously active at all stages of tadpole development studied, but their population activity never coalesces into waves. Even at the earliest stages recorded, visual stimulation dominates over spontaneous activity and can generate patterns of RGC activity similar to the locally correlated spontaneous activity observed in amniotes. In addition, we show that blocking AMPA and NMDA type glutamate receptors significantly decreases spontaneous activity in young Xenopus retina, but that blocking GABA(A) receptor blockers does not. Our findings indicate that vision drives correlated activity required for topographic map formation. They further suggest that developing retinal circuits in the two major subdivisions of tetrapods, amphibians and amniotes, evolved different strategies to supply appropriately patterned RGC activity to drive visual circuit refinement.     

An instructive role for patterned spontaneous retinal activity in mouse visual map development

Complex neural circuits in the mammalian brain develop through a combination of genetic instruction and activity-dependent refinement. The relative role of these factors and the form of neuronal activity responsible for circuit development is a matter of significant debate. In the mammalian visual system, retinal ganglion cell projections to the brain are mapped with respect to retinotopic location and eye of origin. We manipulated the pattern of spontaneous retinal waves present during development without changing overall activity levels through the transgenic expression of β2-nicotinic acetylcholine receptors in retinal ganglion cells of mice. We used this manipulation to demonstrate that spontaneous retinal activity is not just permissive, but instructive in the emergence of eye-specific segregation and retinotopic refinement in the mouse visual system. This suggests that specific patterns of spontaneous activity throughout the developing brain are essential in the emergence of specific and distinct patterns of neuronal connectivity.     

Cerebral cortex: the singular precision of visual cortex maps

A remarkable new technique, two-photon confocal fluorescence microscopy, has revealed an extraordinarily precise organization in the visual cortex. The methodology seems set to become the tool of choice for studying cortical maps.     

Pattern and correlation of fast and slow spontaneous unit activity in the visual cortex

Spontaneous unit activity in the visual cortex and its changes during stimulation by continuous light or flashes were investigated in waking rabbits. The study of distributions of adjacent intervals showed that the neurons differ in the ratio of burst (fast, with intervals of up to 15–40 msec) and nonburst (slow) activity and in the character of changes from one type of activity to the other. Of the total number of spikes 63% were outside bursts; the ratio of their number to the number of spikes within bursts consisting of two or of three or more spikes was 27:3:1. The relative stability of the burst structure of spontaneous activity and the limited number of spikes in them (on average 2.4) were demonstrated. Bursts of three or more spikes (mean 3.6) were irregular, and in 79% of them a longer interval (18.6±2.4 msec) was observed before the shortest interval (7.9±0.9 msec). Bursts of spikes of most neurons during photic stimulation contain more spikes with shorter intervals; they also began more frequently with the shortest interval, possibly signifying an increase in the steepness and amplitude of the EPSPs lying at their basis. However, in 20% of neurons spontaneous bursts included more spikes and with shorter intervals than bursts evoked by flash stimulation.Research Institute of Psychiatry, Ministry of Health of the RSFSR, Moscow. Translated from Neirofiziologiya, Vol. 11, No. 4, pp. 311–320, July–August, 1979.     

Cortical development: the sources of spontaneous patterned activity

A recent study has found that spontaneous neural activity in the developing visual cortex has two distinct origins - local intracortical circuits and spontaneous activity in the retina.     

Ephrin-as guide the formation of functional maps in the visual cortex

Ephrin-As and their receptors, EphAs, are expressed in the developing cortex where they may act to organize thalamic inputs. Here, we map the visual cortex (V1) in mice deficient for ephrin-A2, -A3, and -A5 functionally, using intrinsic signal optical imaging and microelectrode recording, and structurally, by anatomical tracing of thalamocortical projections. V1 is shifted medially, rotated, and compressed and its internal organization is degraded. Expressing ephrin-A5 ectopically by in utero electroporation in the lateral cortex shifts the map of V1 medially, and expression within V1 disrupts its internal organization. These findings indicate that interactions between gradients of EphA/ephrin-A in the cortex guide map formation, but that factors other than redundant ephrin-As are responsible for the remnant map. Together with earlier work on the retinogeniculate map, the current findings show that the same molecular interactions may operate at successive stages of the visual pathway to organize maps.     

Relationship of correlated spontaneous activity to functional ocular dominance columns in the developing visual cortex

Utilizing a multielectrode array to record spontaneous and visually evoked activity of cortical neurons in area 17, we investigate the relationship between long-range correlated spontaneous activity and functional ocular dominance columns during early ferret postnatal development (P24-P29). In regions of visual cortex containing alternating ocular dominance patches, periodic fluctuations in correlated activity are observed in which spontaneous activity is most highly correlated between cortical patches exhibiting the same eye preference. However, these fluctuations are present even within large contralateral eye-dominated bands which lack any periodic alternations in ocular dominance. Thus, the organization of ocular dominance columns cannot fully account for the patterns of correlated activity we observe. Our results suggest that patterns of long-range correlated activity reflect an intrinsic periodicity of cortical connectivity that is constrained by segregated eye-specific LGN afferents.     

Pairing-induced changes of orientation maps in cat visual cortex.

We have studied the precise temporal requirements for plasticity of orientation preference maps in kitten visual cortex. Pairing a brief visual stimulus with electrical stimulation in the cortex, we found that the relative timing determines the direction of plasticity: a shift in orientation preference toward the paired orientation occurs if the cortex is activated first visually and then electrically; the cortical response to the paired orientation is diminished if the sequence of visual and electrical activation is reversed. We furthermore show that pinwheel centers are less affected by the pairing than the pinwheel surround. Thus, plasticity is not uniformly distributed across the cortex, and, most importantly, the same spike time-dependent learning rules that have been found in single-cell in vitro studies are also valid on the level of cortical maps.     

Proprioceptive alignment of visual and somatosensory maps in the posterior parietal cortex

A touch on one hand can enhance the response to a visual stimulus delivered at a nearby location [1, 2], improving our interactions with the external world. In order to keep such visual-tactile spatial interactions effective, the brain updates the continuous postural changes, like those typically accompanying hand actions, through proprioception, thus maintaining the somatosensory and visual maps in spatial register [2, 3]. The posterior parietal cortex (PPC) might be critical for such a spatial remapping [4]; nevertheless, a direct causal demonstration of its involvement is lacking. Here, we found that unattended touches to one hand enhanced visual sensitivity for phosphenes induced by occipital trancranial magnetic stimulation (TMS) [5] when the touched hand was spatially coincident to the reported location of the phosphenes in external space. Notably, this spatially specific crossmodal facilitation was maintained after hand crossing, suggesting an efficient visual-tactile remapping. Critically, after 1 Hz repetitive TMS interference [6] over the PPC, but not over the primary somatosensory cortex, phosphene detection was still enhanced by spatially coincident touches with uncrossed hands, but it was enhanced by spatially noncoincident touches after hand crossing. This is the first causal evidence in humans that the PPC constantly updates the representation of the body in space in order to facilitate crossmodal interactions.     

Spontaneously emerging direction selectivity maps in visual cortex through STDP

It is still an open question as to whether, and how, direction-selective neuronal responses in primary visual cortex are generated by feedforward thalamocortical or recurrent intracortical connections, or a combination of both. Here we present an investigation that concentrates on and, only for the sake of simplicity, restricts itself to intracortical circuits, in particular, with respect to the developmental aspects of direction selectivity through spike-timing-dependent synaptic plasticity. We show that directional responses can emerge in a recurrent network model of visual cortex with spiking neurons that integrate inputs mainly from a particular direction, thus giving rise to an asymmetrically shaped receptive field. A moving stimulus that enters the receptive field from this (preferred) direction will activate a neuron most strongly because of the increased number and/or strength of inputs from this direction and since delayed isotropic inhibition will neither overlap with, nor cancel excitation, as would be the case for other stimulus directions. It is demonstrated how direction-selective responses result from spatial asymmetries in the distribution of synaptic contacts or weights of inputs delivered to a neuron by slowly conducting intracortical axonal delay lines. By means of spike-timing-dependent synaptic plasticity with an asymmetric learning window this kind of coupling asymmetry develops naturally in a recurrent network of stochastically spiking neurons in a scenario where the neurons are activated by unidirectionally moving bar stimuli and even when only intrinsic spontaneous activity drives the learning process. We also present simulation results to show the ability of this model to produce direction preference maps similar to experimental findings     

Patterns of correlated spontaneous bursting activity in the developing mammalian retina

The adult visual system is highly organized in its patterns of connectivity. Connections between the retina and its central target, the dorsal lateral geniculate nucleus (dLGN), are remodeled during development as inappropriate synaptic inputs are eliminated by a process that requires retinal activity. Multineuronal recordings of the neonatal ferret retina reveal that during the refinement period, retinal ganglion cells spontaneously display rhythmic bursting activity in which the bursts of neighboring cells are correlated by propagating excitatory waves. These spontaneous retinal waves have temporal and spatial properties that appear instructive for the refinement of the early patterns of retinogeniculate connections prior to visual stimulation.     

Acetylcholinesterase activity in visual cortex structures during early visual deprivation

By means of quantitative histochemical methods it has been shown that an early photic deprivation (animals kept in a dark chamber for two months after their birth) leads to a decrease in the activity level of acetylcholinesterase (AChE) in the visual area of the cerebral cortex. With the recovery of the visual function (animals kept in normal photic conditions for two weeks) the AChE activity becomes markedly normalized. The obtained data allow to suggest that the decrease in AChE activity due to deprivation is functionally determined.     

Development of phosphodiesterase activity in the chick retina

Significant cyclic GMP phosphodiesterase activity is apparent in the early stages of development of the chick neural retina. By day 8, specific activity drops by approximately two-thirds. After day 14, a sharp rise in activity is observed, continuing through the time of hatching. Cyclic AMP phosphodiesterase activity is considerably lower and does not markedly change over the embryonic period.     

Innate visual learning through spontaneous activity patterns

Patterns of spontaneous activity in the developing retina, LGN, and cortex are necessary for the proper development of visual cortex. With these patterns intact, the primary visual cortices of many newborn animals develop properties similar to those of the adult cortex but without the training benefit of visual experience. Previous models have demonstrated how V1 responses can be initialized through mechanisms specific to development and prior to visual experience, such as using axonal guidance cues or relying on simple, pairwise correlations on spontaneous activity with additional developmental constraints. We argue that these spontaneous patterns may be better understood as part of an "innate learning" strategy, which learns similarly on activity both before and during visual experience. With an abstraction of spontaneous activity models, we show how the visual system may be able to bootstrap an efficient code for its natural environment prior to external visual experience, and we continue the same refinement strategy upon natural experience. The patterns are generated through simple, local interactions and contain the same relevant statistical properties of retinal waves and hypothesized waves in the LGN and V1. An efficient encoding of these patterns resembles a sparse coding of natural images by producing neurons with localized, oriented, bandpass structure-the same code found in early visual cortical cells. We address the relevance of higher-order statistical properties of spontaneous activity, how this relates to a system that may adapt similarly on activity prior to and during natural experience, and how these concepts ultimately relate to an efficient coding of our natural world.     

Recognition of visual stimuli from multiple neuronal activity in monkey visual cortex

Response patterns recorded with 30 microelectrodes from area 17 of anaesthetized monkeys are analysed. A proportion of the patterns are used to define prototype response patterns. These in turn are used to recognize the stimulus from further non-averaged response patterns. In comparison, recognition by a feedforward neural network is much slower, and slightly inferior. The excitation time structure, with a resolution of about 20 ms, is found to contribute strongly to the recognition. There is some inter-ocular recognition for oriented moving bars, and for on and off phases of switched lights, but none for colours. Generalizations over some stimulus parameters (i.e. cases of confusion) are examined: If small jerking shapes are incorrectly recognized, in general the jerk direction often is the correct one. The onset of a response can most easily be found by determining the dissimilarity relative to spontaneous activity in a sliding window.     

Cue-triggered activity replay in human early visual cortex

The recall of learned temporal sequences by a visual cue is an important form of experience-based neural plasticity. Here we observed such reactivation in awake human visual cortex using intracranial recording. After repeated exposure to a moving dot, a flash of the dot was able to trigger neural reactivation in the downstream receptive field along the motion path. This effect was observed only when the cue appeared near the receptive field. The estimated traveling speed was faster compared to the activation induced by the real motion. We suggest a range-limited, time-compressed reactivation as a result of repeated visual exposure in awake human visual cortex.