Filled/non-filled pairs: an empirical challenge to the integrated information theory of consciousness

Perceptual filling-in for vision is the insertion of visual properties (e.g., color, contour, luminance, or motion) into one’s visual field, when those properties have no corresponding retinal input. This paper introduces and provides preliminary empirical support for filled/non-filled pairs, pairs of images that appear identical, yet differ by amount of filling-in. It is argued that such image pairs are important to the experimental testing of theories of consciousness. We review recent experimental research and conclude that filling-in involves brain activity with relatively high integrated information (Phi) compared to veridical visual perceptions. We then present filled/non-filled pairs as an empirical challenge to the integrated information theory of consciousness, which predicts that phenomenologically identical experiences depend on brain processes with identical Phi.

Retinal input influences pace of neurogenesis but not cell-type configuration of the visual forebrain

The brain is assembled during development by both innate and experience-dependent mechanisms1-7, but the relative contribution of these factors is poorly understood. Axons of retinal ganglion cells (RGCs) connect the eye to the brain, forming a bottleneck for the transmission of visual information to central visual areas. RGCs secrete molecules from their axons that control proliferation, differentiation and migration of downstream components7-9. Spontaneously generated waves of retinal activity, but also intense visual stimulation, can entrain responses of RGCs10 and central neurons11-16. Here we asked how the cellular composition of central targets is altered in a vertebrate brain that is depleted of retinal input throughout development. For this, we first established a molecular catalog17 and gene expression atlas18 of neuronal subpopulations in the retinorecipient areas of larval zebrafish. We then searched for changes in lakritz (atoh7-) mutants, in which RGCs do not form19. Although individual forebrain-expressed genes are dysregulated in lakritz mutants, the complete set of 77 putative neuronal cell types in thalamus, pretectum and tectum are present. While neurogenesis and differentiation trajectories are overall unaltered, a greater proportion of cells remain in an uncommitted progenitor stage in the mutant. Optogenetic stimulation of a pretectal area20,21 evokes a visual behavior in blind mutants indistinguishable from wildtype. Our analysis shows that, in this vertebrate visual system, neurons are produced more slowly, but specified and wired up in a proper configuration in the absence of any retinal signals.

Blind cavefish retain functional connectivity in the tectum despite loss of retinal input

Sensory systems display remarkable plasticity and are under strong evolutionary selection. The Mexican cavefish, Astyanax mexicanus, consists of eyed river-dwelling surface populations, and multiple independent cave populations which have converged on eye loss, providing the opportunity to examine the evolution of sensory circuits in response to environmental perturbation. Functional analysis across multiple transgenic populations expressing GCaMP6s showed that functional connectivity of the optic tectum largely did not differ between populations, except for the selective loss of negatively correlated activity within the cavefish tectum, suggesting positively correlated neural activity is resistant to an evolved loss of input from the retina. Further, analysis of surface-cave hybrid fish reveals that changes in the tectum are genetically distinct from those encoding eye-loss. Together, these findings uncover the independent evolution of multiple components of the visual system and establish the use of functional imaging in A. mexicanus to study neural circuit evolution.

Intrinsic circadian timekeeping properties of the thalamic lateral geniculate nucleus

Circadian rhythmicity in mammals is sustained by the central brain clock - the suprachiasmatic nucleus of the hypothalamus (SCN), entrained to the ambient light-dark conditions through a dense retinal input. However, recent discoveries of autonomous clock gene expression cast doubt on the supremacy of the SCN and suggest circadian timekeeping mechanisms devolve to local brain clocks. Here we use a combination of molecular, electrophysiological and optogenetic tools to evaluate intrinsic clock properties of the main retinorecipient thalamic centre - the lateral geniculate nucleus (LGN). We identify the dorsolateral geniculate nucleus (DLG) as a slave oscillator, which exhibits core clock gene expression exclusively in vivo. Additionally, we provide compelling evidence for intrinsic clock gene expression accompanied by circadian variation in neuronal activity in the intergeniculate leaflet (IGL) and ventrolateral geniculate nucleus (VLG). Finally, our optogenetic experiments propose the VLG as a light-entrainable oscillator, whose phase may be advanced by retinal input at the beginning of the projected night. Altogether, this study for the first time demonstrates autonomous timekeeping mechanisms shaping circadian physiology of the LGN.

Finger representation in the cortex of the congenitally blind

Hand representation in the primary somatosensory cortex (S1) is thought to be shaped by experience. Individuals with congenital blindness rely on their sense of touch for completing daily tasks that in sighted people would be informed by vision, and possess superior tactile acuity. It has therefore been proposed that their S1 hand representation should differ from that of sighted individuals. Alternatively, it has been proposed that the improved tactile acuity in blind individuals is due to cross-modal plasticity, when regions in the occipital and temporal cortex are typically used for processing vision become activated by touch. We probed finger representation using psychophysics and 7T fMRI (1 mm3 resolution) in three individuals with bilateral anophthalmia, a rare condition in which both eyes fail to develop, as well as sighted controls. Despite anophthalmic individuals’ increased reliance on touch and superior tactile acuity, we found no evidence that they had more pronounced hand representation in S1. This is in line with recent research highlighting the stability of early sensory cortex, despite altered sensorimotor experience in adulthood. Unlike sighted controls, anophthalmic individuals activated the left human middle temporal complex (hMT+) during finger movement. This area did not express any hallmark of typical sensorimotor organisation, suggesting this and previously reported activity does not indicate low-level sensorimotor hand representation. However, left hMT+ contained some single finger information, beyond that found in sighted controls. This latter finding suggests that when the developmentally flexible area hMT+ is unaffected by retinal input, it can acquire novel cross-modal processes, which are potentially unrelated to the area’s function in sighted people. As such, our findings highlight the opportunity for other organising principles, beyond domain specific plasticity, in shaping cross-modal reorganisation.

Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation

The development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical circuits. These glutamatergic connections are mediated by glutamate receptors including AMPA and NMDA receptors and the ratio of AMPA to NMDA receptors decreases during development. Since previous studies have shown that retinal input can regulate the early development of connections along the visual pathway, we investigated if the maturation of glutamatergic inputs to GABAergic interneurons in the visual cortex requires retinal input. We mapped the spatial pattern of glutamatergic connections to layer 4 (L4) GABAergic interneurons in mouse visual cortex at around postnatal day (P) 16 by laser-scanning photostimulation and investigated the effect of binocular enucleations at P1/P2 on these patterns. Gad2-positive interneurons in enucleated animals showed an increased fraction of AMPAR-mediated input from L2/3 and a decreased fraction of input from L5/6. Parvalbumin-expressing (PV) interneurons showed similar changes in relative connectivity. NMDAR-only input was largely unchanged by enucleation. Our results show that retinal input sculpts the integration of interneurons into V1 circuits and suggest that the development of AMPAR- and NMDAR-only connections might be regulated differently.

Illusory size determines the perception of ambiguous apparent motion

The visual system constructs perceptions based on ambiguous information. For motion perception, the correspondence problem arises, i.e., the question of which object went where. We asked at which level of processing correspondence is solved – lower levels based on information that is directly available in the retinal input or higher levels based on information that has been abstracted beyond the input directly available at the retina? We used a Ponzo-like illusion to manipulate the perceived size and separations of elements in an ambiguous apparent motion display. Specifically, we presented Ternus displays – for which the type of motion that is perceived depends on how correspondence is resolved – at apparently different distances from the viewer using pictorial depth cues. We found that the perception of motion depended on the apparent depth of the displays, indicating that correspondence processes utilize information that is produced at higher-level processes.

The Olivary Pretectal Nucleus Receives Visual Input of High Spatial Resolution

In the mouse, retinal output is computed by over 40 distinct types of retinal ganglion cells (RGCs) (Baden et al., 2016). Determining which of these many RGC types project to a retinorecipient region is a key step in elucidating the role that region plays in visually-mediated behaviors. Combining retrograde viral tracing and single-cell electrophysiology, we identify the RGC types which project to the olivary pretectal nucleus (OPN), a major visual structure. We find that retinal input to the OPN consists of a variety of intrinsically-photosensitive and conventional RGC types, the latter a diverse set of mostly ON RGCs. Surprisingly, while the OPN is most associated with the pupillary light reflex (PLR) pathway, requiring information about absolute luminance, we show that the majority of the retinal input to the OPN is from single cell type which transmits information unrelated to luminance. This ON-transient RGC accounts for two-thirds of the input to the OPN, and responds to small objects across a wide range of speeds. This finding suggests a role for the OPN in visually-mediated behaviors beyond the PLR.Significance statementThe olivary pretectal nucleus is a midbrain structure which receives direct input from retinal ganglion cells (RGC), and modulates pupil diameter in response to changing absolute light level. In the present study, we combine viral tracing and electrophysiology to identify the RGC types which project to the OPN. Surprisingly, the majority of its input comes from a single type which does not encode absolute luminance, but instead responds to small objects across a wide range of speeds. These findings are consistent with a role for the OPN apart from pupil control and suggest future experiments to elucidate its full role in visually-mediated behavior.

Photoperiod-Induced Neurotransmitter Switching in the Circadian Pacemaker Regulates Hypothalamic Dopamine Expression

Light, circadian clocks, and rhythmic behaviors interact closely to produce a temporal order that is essential for the survival of most living organisms. In mammals, the principal circadian pacemaker in the brain is the suprachiasmatic nucleus (SCN), which receives direct retinal input and synchronizes itself and other brain regions to the external light-dark cycle. Altered day length (photoperiod) and disrupted circadian rhythms are associated with impaired memory and mood in both humans and animal models. Prior work demonstrated that altering photoperiod can change neurotransmitter (NT) expression in the periventricular nucleus (PeVN) of the hypothalamus in adult rat brain. Here we show that neuromedin S-(NMS-) and vasoactive intestinal polypeptide-(VIP-) expressing neurons in the SCN also display photoperiod-induced neurotransmitter switching. Such photoperiod-dependent NT plasticity is retained in Bmal1-KO mice, indicating that NT plasticity in the SCN does not require a functional circadian clock. Utilizing a conditional viral DO-DIO vector as an historical marker of NT expression in the SCN, we further reveal that short-day photoperiod induces a cluster of non-NMS-expressing neurons to undergo NT switching and acquire the NMS phenotype. Selective chemogenetic activation of NMS neurons, but not VIP neurons, during the dark phase induces a significant delay in the timing of locomotor activity onset and is sufficient to increase the number of dopaminergic neurons in the PeVN. Our findings provide novel insights into molecular adaptations of the SCN neuronal network in response to altered photoperiod that affect neuronal circuit function in the hypothalamus and lead to changes in circadian behavior.