Absence Of Retinal Input Research Articles

Retinal inputs signal astrocytes to recruit interneurons into visual thalamus

Inhibitory interneurons comprise a fraction of the total neurons in the visual thalamus but are essential for sharpening receptive field properties and improving contrast-gain of retinogeniculate transmission. During early development, these interneurons undergo long-range migration from germinal zones, a process regulated by the innervation of the visual thalamus by retinal ganglion cells. Here, using transcriptomic approaches, we identified a motogenic cue, fibroblast growth factor 15 (FGF15), whose expression in the visual thalamus is regulated by retinal input. Targeted deletion of functional FGF15 in mice led to a reduction in thalamic GABAergic interneurons similar to that observed in the absence of retinal input. This loss may be attributed, at least in part, to misrouting of interneurons into nonvisual thalamic nuclei. Unexpectedly, expression analysis revealed that FGF15 is generated by thalamic astrocytes and not retino-recipient neurons. Thus, these data show that retinal inputs signal through astrocytes to direct the long-range recruitment of interneurons into the visual thalamus.

Growth and Behavior of Congenitally Anophthalmic Lee-Sung Pigs.

Circadian rhythm is usually regulated by the environmental light-dark cycle. Congenitally anophthalmic miniature pigs provide a valuable model for the study of factors affecting circadian rhythms in the absence of visual exposure to the light-dark cycle. This study investigated the growth and daily behavior patterns of Lee-Sung pigs with congenital anophthalmia. Growth in 5 Lee-Sung pigs (LSP) with congenital anophthalmia (LSP-A) and 10 normally developed pigs (LSP-N) was assessed when they were 1 through 6 mo old. Behavioral studies using digital video recording were completed in 6 sexually mature LSP (3 LSP-A and 3 LSP-N). MRI showed that LSP-A lose their vision because of a lack of retinal input and optic chiasm development. LSP-N and LSP-A did not differ in body weight or size at 2, 4, and 6 mo of age. Behavior and activity pattern studies showed that both LSP-A and LSP-N were active mainly during daylight, but LSP-A spent significantly more time exploring their environment during the day (28%) and night (10%) than did LSP-N. This study revealed that growth performance was similar between LSP-A and normal pigs, but their behavior and activity patterns differed. LSP-A showed circadian rhythm abnormalities similar to those in blind humans. This study provides basic data on LSP-A as a model for studying compensatory cross-modal brain plasticity and hormone regulation in the absence of retinal input is deficient and for understanding the role of circadian rhythm regulation.

A Possible Explanation of Oriented Bar Filling-in at the Blind- Spot in the light of Hierarchical Prediction Mechanism

Despite the absence of retinal input, the blind-spot gets filled up with surrounding visual attributes. This phenomenon is called the perceptual filling-in or completion. Various possible neural mechanisms have been proposed but most of these are not entirely consistent with the findings of brain activation and brain organization. In one study, recently, it has been shown that the filling-in of the shifting bar and the anisotropy in the filling-in of misaligned bars could be explained by incorporating a common general principle called hierarchical predictive coding (HPC). In this report, we have extended this proposition to explain the filling-in of oriented bars. We have considered a three level (LGN-V1-V2) HPC model network in which, the blind-spot was emulated by removing the corresponding feed-forward (LGN-V1) connection. We simulated the responses of predictive estimator (PE) neurons at blind-spot while stimulating the network with oriented bar stimuli. Results show that the filling-in is best for aligned bars but it faded away with increasing orientation and moreover, corners were not predicted in any orientation. Qualitatively, these results are consistent with the findings of psychophysical experiments. We discussed this phenomenon in the HPC framework and argue that in the absence feed-forward connections, the best prediction is dominated by learned statistical regularities that include an abundance of bar and similar structures. These results suggest that the filling-in process could be a manifestation of HPC.

Resting-State Retinotopic Organization in the Absence of Retinal Input and Visual Experience.

Early visual areas have neuronal receptive fields that form a sampling mosaic of visual space, resulting in a series of retinotopic maps in which the same region of space is represented in multiple visual areas. It is not clear to what extent the development and maintenance of this retinotopic organization in humans depend on retinal waves and/or visual experience. We examined the corticocortical receptive field organization of resting-state BOLD data in normally sighted, early blind, and anophthalmic (in which both eyes fail to develop) individuals and found that resting-state correlations between V1 and V2/V3 were retinotopically organized for all subject groups. These results show that the gross retinotopic pattern of resting-state connectivity across V1-V3 requires neither retinal waves nor visual experience to develop and persist into adulthood. Significance statement: Evidence from resting-state BOLD data suggests that the connections between early visual areas develop and are maintained even in the absence of retinal waves and visual experience.

Visual representation in the absence of retinal input

Visual representation in the absence of retinal input

Visual callosal topography in the absence of retinal input

Using probabilistic diffusion tractography, we examined the retinotopic organization of splenial callosal connections within early blind, anophthalmic, and control subjects. Early blind subjects experienced prenatal retinal “waves” of spontaneous activity similar to those of sighted subjects, and only lack postnatal visual experience. In anophthalmia, the eye is either absent or arrested at an early prenatal stage, depriving these subjects of both pre- and postnatal visual input. Therefore, comparing these two groups provides a way of separating the influence of pre- and postnatal retinal input on the organization of visual connections across hemispheres. We found that retinotopic mapping within the splenium was not measurably disrupted in early blind or anophthalmic subjects compared to visually normal controls. No significant differences in splenial volume were observed across groups. No significant differences in diffusivity were found between early blind subjects and sighted controls, though some differences in diffusivity were noted between anophthalmic subjects and controls. These results suggest that neither prenatal retinal activity nor postnatal visual experience plays a role in the large-scale topographic organization of visual callosal connections within the splenium.

MSTd Neurons Encode Nonlinear Combinations of Retinal and Extra-retinal Signals

AbstractNeuronal activity in the dorsal Medial Superior Temporal area (MSTd) is assumed to depend on both retinal and extra-retinal input. Most of the neurons show activity when presented with a moving large-field visual stimulus. In addition, many MSTd neurons are activated during smooth pursuit eye movements even in the absence of retinal input. However, the interaction between the retinal and extra-retinal input is not yet fully understood.Here we present novel insights regarding the tuning of MSTd neurons for combinations of different input variables using an information-theoretic approach. Neuronal tuning functions can be expressed by the conditional probability of observing a spike given any combination of input variables. However, accurately determining such probabilistic tuning functions from experimental data poses several challenges such as determining the neuronal latencies and finding the combination of input variables which is most related to neuronal activity. Our approach solves these issues by maximizing the mutual information between the probability distributions of spike occurrence and input variables.We analyzed the dependence of MSTd neuronal activity in monkeys on various retinal and extra-retinal signals during presentation of a large-field visual stimulus moving randomly with quasi equally distributed frequencies (white noise). Across the population, neuronal activity depended on different combinations of retinal and extra-retinal input. The interrelation between the input variables exhibited in many cases strong non-linear characteristics. These findings support the hypothesis that MSTd uses a basis function representation for encoding various retinal and extra-retinal signals.

The neuromagnetic correlates of self-initiated smooth pursuit eye movements and finger tracking in the absence of retinal input

The neuromagnetic correlates of self-initiated smooth pursuit eye movements and finger tracking in the absence of retinal input

A multivariate population density model of the dLGN/PGN relay

Using a population density approach we study the dynamics of two interacting collections of integrate-and-fire-or-burst (IFB) neurons representing thalamocortical (TC) cells from the dorsal lateral geniculate nucleus (dLGN) and thalamic reticular (RE) cells from the perigeniculate nucleus (PGN). Each population of neurons is described by a multivariate probability density function that satisfies a conservation equation with appropriately defined probability fluxes and boundary conditions. The state variables of each neuron are the membrane potential and the inactivation gating variable of the low-threshold Ca2+ current I(T). The synaptic coupling of the populations and external excitatory drive are modeled by instantaneous jumps in the membrane potential of postsynaptic neurons. The population density model is validated by comparing its response to time-varying retinal input to Monte Carlo simulations of the corresponding IFB network composed of 100 to 1,000 cells per population. In the absence of retinal input, the population density model exhibits rhythmic bursting similar to the 7 to 14 Hz oscillations associated with slow wave sleep that require feedback inhibition from RE to TC cells. When the TC and RE cell potassium leakage conductances are adjusted to represent cholingergic neuromodulation and arousal of the network, rhythmic bursting of the probability density model may either persists or be eliminated depending on the number of excitatory (TC to RE) or inhibitory (RE to TC) connections made by each presynaptic cell. When the probability density model is stimulated with constant retinal input (10-100 spikes/sec), a wide range of responses are observed depending on cellular parameters and network connectivity. These include asynchronous burst and tonic spikes, sleep spindle-like rhythmic bursting, and oscillations in population firing rate that are distinguishable from sleep spindles due to their amplitude, frequency, or the presence of tonic spikes. In this context of dLGN/PGN network modeling, we find the population density approach using 2,500 mesh points and resolving membrane voltage to 0.7 mV is over 30 times more efficient than 1,000-cell Monte Carlo simulations.

Synaptogenesis in the occipital cortex of macaque monkey devoid of retinal input from early embryonic stages.

The role of input from the retina on the development of synaptic organization in the primate striate cortex was examined in macaque monkeys enucleated at embryonic (E) day 67 and E59. Both the prenatally operated animals and their age-matched controls were delivered at term (E165) and killed either at 3 months (at the end of the rapid phase of synaptogenesis) or 3 years (at the end of the plateau phase of synaptogenesis). As expected, in the operated animals the striate cortex had a smaller surface area but a normal thickness and complement of layers. The present study revealed that the mean densities of synaptic contacts per unit area and volume of neuropil in the striate cortex of the two operated animals were similar to those of age-matched controls (approximately 30/100 microm2 or 100/100 microm3 of neuropil). Thus, the absence of retinal input via the lateral geniculate nucleus did not affect the schedule and magnitude of synaptogenesis. Likewise, the ratio of symmetrical versus asymmetrical synapses and mean lengths of synaptic junctions were within the normal range of variation in both group of animals. The proportions of synaptic contacts situated on dendritic spines and shafts were also similar in supra- and infragranular cortical layers of normal and enucleated animals. However, the ratio of synapses situated on dendritic spines and shafts in the sublayers IVAB and IVC, which normally become reversed during late adolescence, were not reversed in the enucleates. Therefore, our study indicated that certain parameters of synaptic development, such as the density of contacts per unit volume of neuropil and the proportion of basic types and their size, in the supra- and infragranular layers of the striate cortex develop to an optimal normal level in the absence of both retinae from early embryonic stages. However, in the thalamorecipient sublayers the details of the synaptic circuits such as their localization on dendritic spines or shafts, fail to mature properly in the absence of normal functional input from the periphery.

The geniculohypothalamic pathway in a congenitally anophthalmic mouse

In a previous study we described abnormalities in cytoarchitecture and vasoactive intestinal polypeptide distribution in the suprachiasmatic nucleus (SCN) of anophthalmic mice. However, the effect of anopththalmia on the geniculohypothalamic pathway, an important pathway for relay of photic information to the SCN, is not known. The present study examined the geniculohypothalamic pathway in congenitally anophthalmic and sighted control mice. The data demonstrate that the development of an intergeniculate leaflet (IGL), the expression of neuropeptide Y (NPY) by IGL neurons and the formation of NPY terminal fields in the SCN proceed in the absence of retinal input. Although the cytoarchitectural organization of the anophthalmic IGL differs from that of the control mouse, the distribution of NPY plexuses in the suprachiasmatic nucleus is remarkably similar.

Topographic organization of certain tectal afferent and efferent connections can develop normally in the absence of retinal input.

To test the hypothesis that the topographic organization of the connections of the optic tectum is determined during development by the "retinotopically" ordered input that it receives from the eye, we have mapped certain of the connections of the tectum in chicken embryos and chicks in which both eye rudiments were removed before the outgrowth of optic fibers. Because several of the connections of the tectum are normally organized retinotopically, we should expect, if this hypothesis were correct, that some or all of these connectional patterns would be significantly altered in such "eyeless" chickens. In fact, we have found that the connections formed between the optic tectum and two of the isthmic nuclei, with which it is reciprocally connected, show the same topographic organization in "eyeless" animals as in control chickens raised under the same conditions. This clearly indicates that the topographic organization of the chicken optic tectum is independently specified and is not contingent upon the input that it receives from the retina.

Lateral geniculate nucleus unitary discharge in sleep and waking: state- and rate-specific aspects.

The relationship between behavioral state, discharge pattern, and discharge rate was investigated in 26 lateral geniculate nucleus (LGN) units recorded in cats in the dark during waking (W), synchronized sleep (S), and desynchronized sleep (D). A distinctive state-dependent discharge pattern was the presence of stereotyped bursts of 2-7 spikes that occurred in 63% of the units. These bursts were most frequent in S, much less frequent in D, and rarely occurred in W. Lack of association with discharge rate changes between states showed the bursting to be a true state-dependent phenomenon. A burst consisted of 2-7 spikes, with each successive interspike interval being longer than the preceding one; in the 200 ms prior to burst occurrence, discharge probability decreased markedly. This structure of burst organization suggested a model of generation wherein each burst was caused by a unitary event of varying intensity, perhaps a rebound following a hyperpolarization. Spectral and autocorrelational analyses showed bursts occurred rhythmically in three cells at a frequency of 3-4 Hz and in two cells at a frequency of 10-12 Hz, indicating a possible linkage with slow-wave generators. While the number of bursts in the various behavioral states was a state-dependent phenomena, other aspects of discharge pattern were shown to be rate dependent. To evaluate discharge pattern apart from the occurrence of bursts, a "primary event spike train" was formed; this consisted of individual spikes and the first spike of each burst. This analysis showed that, within S, the probability of burst occurrence was highest when the primary spike rate was low. Quantitative analyses showed that first-order pattern measures (the form of the interspike interval histogram, IH) were dependent on the mean interspike interval (ISI, the inverse of mean rate). This association explained 83-89% of the variance in a power series approximation of IH form. Joint interval histograms (JIH) were used to evaluate the signature of bursts and of the form of the primary spike train. As with interval histograms, the main features of the form of the primary spike JIH were dependent on the primary spike rate. Thus, we concluded that first- and second-order discharge patterns of primary events were rate dependent and not state dependent. Our data are compatible with a model where in the absence of retinal input, the frequency of LGN primary spikes over behavioral state changes is largely determined by brain stem reticular formation input.(ABSTRACT TRUNCATED AT 400 WORDS)