Multiple Visuotopically Organized Subdivisions of the Lateral Pulvinar/Central Lateral Inferior Pulvinar Project into Thin and Thick Stripe Compartments of V2 in Macaques.

The lateral and central lateral inferior pulvinar (PL/PIcl) of primates has been implicated in playing an important role in visual processing, but its physiological and anatomical characteristics remain to be elucidated. It has been suggested that there are two complete visuotopic maps in the PL/PIcl, each of which sends afferents into V2 and V4 in primates. Given that functionally distinct thin and thick stripes of V2 both receive inputs from the PL/PIcl, this raises the possibility of a presence of parallel segregated pathways within the PL/PIcl. To address this question, we selectively injected three types of retrograde tracers (CTB-488, CTB-555, and BDA) into thin or thick stripes in V2 and examined labeling in the PL/PIcl in macaques. As a result, we found that every cluster of retrograde labeling in the PL/PIcl included all three types of signals next to each other, suggesting that thin stripe- and thick stripe-projecting compartments are not segregated into domains. Unexpectedly, we found at least five topographically organized retrograde labeling clusters in the PL/PIcl, indicating the presence of more than two V2-projecting maps. Our results suggest that the PL/PIcl exhibits greater compartmentalization than previously thought. They may be functionally similar but participate in multiple cortico-pulvinar-cortical loops.

The visual white matter connecting human area prostriata and the thalamus is retinotopically organized.

The human visual system is capable of processing visual information from fovea to the far peripheral visual field. Recent fMRI studies have shown a full and detailed retinotopic map in area prostriata, located ventro-dorsally and anterior to the calcarine sulcus along the parieto-occipital sulcus with strong preference for peripheral and wide-field stimulation. Here, we report the anatomical pattern of white matter connections between area prostriata and the thalamus encompassing the lateral geniculate nucleus (LGN). To this end, we developed and utilized an automated pipeline comprising a series of Apps that run openly on the cloud computing platform brainlife.io to analyse 139 subjects of the Human Connectome Project (HCP). We observe a continuous and extended bundle of white matter fibers from which two subcomponents can be extracted: one passing ventrally parallel to the optic radiations (OR) and another passing dorsally circumventing the lateral ventricle. Interestingly, the loop travelling dorsally connects the thalamus with the central visual field representation of prostriata located anteriorly, while the other loop travelling more ventrally connects the LGN with the more peripheral visual field representation located posteriorly. We then analyse an additional cohort of 10 HCP subjects using a manual plane extraction method outside brainlife.io to study the relationship between the two extracted white matter subcomponents and eccentricity, myelin and cortical thickness gradients within prostriata. Our results are consistent with a retinotopic segregation recently demonstrated in the OR, connecting the LGN and V1 in humans and reveal for the first time a retinotopic segregation regarding the trajectory of a fiber bundle between the thalamus and an associative visual area.

Cortical and thalamic connectivity of posterior parietal visual cortical areas PPc and PPr of the domestic ferret (Mustela putorius furo).

The present study describes the ipsilateral and contralateral cortico-cortical and cortico-thalamic connectivity of the parietal visual areas, posterior parietal caudal cortical area (PPc) and posterior parietal rostral cortical area (PPr), in the ferret using standard anatomical tract-tracing methods. The two divisions of posterior parietal cortex of the ferret are strongly interconnected, however area PPc shows stronger connectivity with the occipital and suprasylvian visual cortex, while area PPr shows stronger connectivity with the somatomotor cortex, reflecting the functional specificity of these two areas. This pattern of connectivity is mirrored in the contralateral callosal connections. In addition, PPc and PPr are connected with the visual and somatomotor nuclei of the dorsal thalamus. Numerous connectional similarities exist between the posterior parietal cortex of the ferret (PPc and PPr) and the cat (area 7 and 5), indicative of the homology of these areas within the Carnivora. These findings highlight the existence of a frontoparietal network as a shared feature of the organization of parietal cortex across Euarchontoglires and Laurasiatherians, with the degree of expression varying in relation to the expansion and areal complexity of the posterior parietal cortex. This observation indicates that the ferret is a potentially valuable experimental model animal for understanding the evolution and function of the posterior parietal cortex and the frontoparietal network across mammals. The data generated will also contribute to a connectomics database, to further cross-species analyses of connectomes and illuminate wiring principles of cortical connectivity across mammals.

Cortical and thalamic connectivity of occipital visual cortical areas 17, 18, 19, and 21 of the domestic ferret (Mustela putorius furo).

The present study describes the ipsilateral and contralateral corticocortical and corticothalamic connectivity of the occipital visual areas 17, 18, 19, and 21 in the ferret using standard anatomical tract-tracing methods. In line with previous studies of mammalian visual cortex connectivity, substantially more anterograde and retrograde label was present in the hemisphere ipsilateral to the injection site compared to the contralateral hemisphere. Ipsilateral reciprocal connectivity was the strongest within the occipital visual areas, while weaker connectivity strength was observed in the temporal, suprasylvian, and parietal visual areas. Callosal connectivity tended to be strongest in the homotopic cortical areas, and revealed a similar areal distribution to that observed in the ipsilateral hemisphere, although often less widespread across cortical areas. Ipsilateral reciprocal connectivity was observed throughout the visual nuclei of the dorsal thalamus, with no contralateral connections to the visual thalamus being observed. The current study, along with previous studies of connectivity in the cat, identified the posteromedial lateral suprasylvian visual area (PMLS) as a distinct network hub external to the occipital visual areas in carnivores, implicating PMLS as a potential gateway to the parietal cortex for dorsal stream processing. These data will also contribute to a macro connectome database of the ferret brain, providing essential data for connectomics analyses and cross-species analyses of connectomes and brain connectivity matrices, as well as providing data relevant to additional studies of cortical connectivity across mammals and the evolution of cortical connectivity variation.

Cortical and thalamic connectivity of temporal visual cortical areas 20a and 20b of the domestic ferret (Mustela putorius furo).

The present study describes the ipsilateral and contralateral corticocortical and corticothalamic connectivity of the temporal visual areas 20a and 20b in the ferret using standard anatomical tract-tracing methods. The two temporal visual areas are strongly interconnected, but area 20a is primarily connected to the occipital visual areas, whereas area 20b maintains more widespread connections with the occipital, parietal and suprasylvian visual areas and the secondary auditory cortex. The callosal connectivity, although homotopic, consists mainly of very weak anterograde labeling which was more widespread in area 20a than area 20b. Although areas 20a and 20b are well connected with the visual dorsal thalamus, the injection into area 20a resulted in more anterograde label, whereas more retrograde label was observed in the visual thalamus following the injection into area 20b. Most interestingly, comparisons to previous connectional studies of cat areas 20a and 20b reveal a common pattern of connectivity of the temporal visual cortex in carnivores, where the posterior parietal cortex and the central temporal region (PMLS) provide network points required for dorsal and ventral stream interaction enroute to integration in the prefrontal cortex. This pattern of network connectivity is not dissimilar to that observed in primates, which highlights the ferret as a useful animal model to understand visual sensory integration between the dorsal and ventral streams. The data generated will also contribute to a connectomics database, to facilitate cross species analysis of brain connectomes and wiring principles of the brain.

Tractography optimization using quantitative T1 mapping in the human optic radiation.

Diffusion MRI tractography is essential for reconstructing white-matter projections in the living human brain. Yet tractography results miss some projections and falsely identify others. A challenging example is the optic radiation (OR) that connects the thalamus and the primary visual cortex. Here, we tested whether OR tractography can be optimized using quantitative T1 mapping. Based on histology, we proposed that myelin-sensitive T1 values along the OR should remain consistently low compared with adjacent white matter. We found that complementary information from the T1 map allows for increasing the specificity of the reconstructed OR tract by eliminating falsely identified projections. This T1-filtering outperforms other, diffusion-based tractography filters. These results provide evidence that the smooth microstructural signature along the tract can be used as constructive input for tractography. Finally, we demonstrate that this approach can be applied in a case of multiple sclerosis, and generalized to the HCP-available MRI measurements. We conclude that multimodal MRI microstructural information can be used to eliminate spurious tractography results in the case of the OR.

LRRTM1 underlies synaptic convergence in visual thalamus.

It has long been thought that the mammalian visual system is organized into parallel pathways, with incoming visual signals being parsed in the retina based on feature (e.g. color, contrast and motion) and then transmitted to the brain in unmixed, feature-specific channels. To faithfully convey feature-specific information from retina to cortex, thalamic relay cells must receive inputs from only a small number of functionally similar retinal ganglion cells. However, recent studies challenged this by revealing substantial levels of retinal convergence onto relay cells. Here, we sought to identify mechanisms responsible for the assembly of such convergence. Using an unbiased transcriptomics approach and targeted mutant mice, we discovered a critical role for the synaptic adhesion molecule Leucine Rich Repeat Transmembrane Neuronal 1 (LRRTM1) in the emergence of retinothalamic convergence. Importantly, LRRTM1 mutant mice display impairment in visual behaviors, suggesting a functional role of retinothalamic convergence in vision.

Optic nerve, superior colliculus, visual thalamus, and primary visual cortex of the northern elephant seal (Mirounga angustirostris) and California sea lion (Zalophus californianus).

The northern elephant seal (Mirounga angustirostris) and California sea lion (Zalophus californianus) are members of a diverse clade of carnivorous mammals known as pinnipeds. Pinnipeds are notable for their large, ape-sized brains, yet little is known about their central nervous system. Both the northern elephant seal and California sea lion spend most of their lives at sea, but each also spends time on land to breed and give birth. These unique coastal niches may be reflected in specific evolutionary adaptations to their sensory systems. Here, we report on components of the visual pathway in these two species. We found evidence for two classes of myelinated fibers within the pinniped optic nerve, those with thick myelin sheaths (elephant seal: 9%, sea lion: 7%) and thin myelin sheaths (elephant seal: 91%, sea lion: 93%). In order to investigate the architecture of the lateral geniculate nucleus, superior colliculus, and primary visual cortex, we processed brain sections from seal and sea lion pups for Nissl substance, cytochrome oxidase, and vesicular glutamate transporters. As in other carnivores, the dorsal lateral geniculate nucleus consisted of three main layers, A, A1, and C, while each superior colliculus similarly consisted of seven distinct layers. The sea lion visual cortex is located at the posterior side of cortex between the upper and lower banks of the postlateral sulcus, while the elephant seal visual cortex extends far more anteriorly along the dorsal surface and medial wall. These results are relevant to comparative studies related to the evolution of large brains.

Geniculo-Cortical Projection Diversity Revealed within the Mouse Visual Thalamus.

The mouse dorsal lateral geniculate nucleus (dLGN) is an intermediary between retina and primary visual cortex (V1). Recent investigations are beginning to reveal regional complexity in mouse dLGN. Using local injections of retrograde tracers into V1 of adult and neonatal mice, we examined the developing organisation of geniculate projection columns: the population of dLGN-V1 projection neurons that converge in cortex. Serial sectioning of the dLGN enabled the distribution of labelled projection neurons to be reconstructed and collated within a common standardised space. This enabled us to determine: the organisation of cells within the dLGN-V1 projection columns; their internal organisation (topology); and their order relative to V1 (topography). Here, we report parameters of projection columns that are highly variable in young animals and refined in the adult, exhibiting profiles consistent with shell and core zones of the dLGN. Additionally, such profiles are disrupted in adult animals with reduced correlated spontaneous activity during development. Assessing the variability between groups with partial least squares regression suggests that 4-6 cryptic lamina may exist along the length of the projection column. Our findings further spotlight the diversity of the mouse dLGN--an increasingly important model system for understanding the pre-cortical organisation and processing of visual information. Furthermore, our approach of using standardised spaces and pooling information across many animals will enhance future functional studies of the dLGN.

Morphological properties of tectal neurons that project to the nucleus geniculatus lateralis, pars ventralis (GLv) and the surrounding ventral thalamus in chicks.

Layer 10 neurons of the chick tectum were morphologically investigated. The layer 10 neurons displayed heterogeneous immunoreactivities to calcium-binding proteins (CaBPs). Calbindin (CB)-immunoreactive (ir) neurons had pyramidal or round somata, primarily found in layers 5, 9, and 13. Parvalbumin (PV)-ir neurons were of various shapes with small to large somata (109.7±48.6µm(2)) that were located mainly in layers 4 and 10. Calretinin (CR)-ir neurons had small to middle-sized somata (79.3±9.7µm(2)) located primarily in layers 10 and 13, and most of them were similar to typical radial cells in size and shape. Two distinct types of neurons that projected to the nucleus geniculatus lateralis, pars ventralis (GLv) and ventral thalamus were demonstrated in layer 10. Type 1 cells had small to middle-sized somata (74.3±33µm(2)), and each cell had a single apical dendrite that ramified into bush-like branches in layer 7. These cells corresponded to CR-ir neurons and radial cells in size and shape. Type 2 cells had larger somata (124.7±52.6µm(2)), and their shapes were pyramidal, polygonal, or oval. They had multiple obliquely ascending dendrites that ramified into bush-like branches in layer 7. These cells often appeared similar to PV-ir neurons.

What can mice tell us about how vision works?

Understanding the neural basis of visual perception is a long-standing fundamental goal of neuroscience. Historically, most vision studies were carried out on humans, macaques and cats. Over the past 5 years, however, a growing number of researchers have begun using mice to parse the mechanisms underlying visual processing; the rationale is that, despite having relatively poor acuity, mice are unmatched in terms of the variety and sophistication of tools available to label, monitor and manipulate specific cell types and circuits. In this review, we discuss recent advances in understanding the mouse visual system at the anatomical, receptive field and perceptual level, focusing on the opportunities and constraints those features provide toward the goal of understanding how vision works.

Superior colliculus connections with visual thalamus in gray squirrels (Sciurus carolinensis): evidence for four subdivisions within the pulvinar complex.

As diurnal rodents with a well-developed visual system, squirrels provide a useful comparison of visual system organization with other highly visual mammals such as tree shrews and primates. Here, we describe the projection pattern of gray squirrel superior colliculus (SC) with the large and well-differentiated pulvinar complex. Our anatomical results support the conclusion that the pulvinar complex of squirrels consists of four distinct nuclei. The caudal (C) nucleus, distinct in cytochrome oxidase (CO), acetylcholinesterase (AChE), and vesicular glutamate transporter-2 (VGluT2) preparations, received widespread projections from the ipsilateral SC, although a crude retinotopic organization was suggested. The caudal nucleus also received weaker projections from the contralateral SC. The caudal nucleus also projects back to the ipsilateral SC. Lateral (RLl) and medial (RLm) parts of the previously defined rostral lateral pulvinar (RL) were architectonically distinct, and each nucleus received its own retinotopic pattern of focused ipsilateral SC projections. The SC did not project to the rostral medial (RM) nucleus of the pulvinar. SC injections also revealed ipsilateral connections with the dorsal and ventral lateral geniculate nuclei, nuclei of the pretectum, and nucleus of the brachium of the inferior colliculus and bilateral connections with the parabigeminal nuclei. Comparisons with other rodents suggest that a variously named caudal nucleus, which relays visual inputs from the SC to temporal visual cortex, is common to all rodents and possibly most mammals. RM and RL divisions of the pulvinar complex also appear to have homologues in other rodents.

Adaptive changes in firing of primary auditory cortical neurons following illumination shift from light to dark in freely moving guinea pigs.

Some animals are forced to rely more on non-visual signals, such as audition or olfaction, than on vision when a bright environment becomes dark. By recording from a primary-like auditory cortex (field A) in freely moving guinea pigs, possible changes in the responsiveness of single units were explored in association with illumination changes. For a subset of units, we found that robust decreases (off-decrease) or increases (off-increase) in baseline discharge (BsD) were initiated soon after room light was silently extinguished. These neuronal changes were accompanied by the initiation of explorative locomotion, possibly reflecting a changed internal brain state. Preferred acoustic stimuli evoked salient excitatory responses against the reduced BsD level in the dark for the off-decrease units, and salient inhibitory responses against the increased BsD level for the off-increase units. Histological verification indicated that the units showing such BsD changes were located predominantly in layer V or its vicinity. These results are discussed in the context of the effects of the brainstem neuromodulatory systems that are activated during behavioral adaptation to new environments.

Differential gene expression in the developing lateral geniculate nucleus and medial geniculate nucleus reveals novel roles for Zic4 and Foxp2 in visual and auditory pathway development.

Primary sensory nuclei of the thalamus process and relay parallel channels of sensory input into the cortex. The developmental processes by which these nuclei acquire distinct functional roles are not well understood. To identify novel groups of genes with a potential role in differentiating two adjacent sensory nuclei, we performed a microarray screen comparing perinatal gene expression in the principal auditory relay nucleus, the medial geniculate nucleus (MGN), and principal visual relay nucleus, the lateral geniculate nucleus (LGN). We discovered and confirmed groups of highly ranked, differentially expressed genes with qRT-PCR and in situ hybridization. A functional role for Zic4, a transcription factor highly enriched in the LGN, was investigated using Zic4-null mice, which were found to have changes in topographic patterning of retinogeniculate projections. Foxp2, a transcriptional repressor expressed strongly in the MGN, was found to be positively regulated by activity in the MGN. These findings identify roles for two differentially expressed genes, Zic4 and Foxp2, in visual and auditory pathway development. Finally, to test whether modality-specific patterns of gene expression are influenced by extrinsic patterns of input, we performed an additional microarray screen comparing the normal MGN to "rewired" MGN, in which normal auditory afferents are ablated and novel retinal inputs innervate the MGN. Data from this screen indicate that rewired MGN acquires some patterns of gene expression that are present in the developing LGN, including an upregulation of Zic4 expression, as well as novel patterns of expression which may represent unique processes of cross-modal plasticity.

Purinergic modulation in the development of the rat uncrossed retinotectal pathway.

Adenosine is a neuromodulator implicated in nervous system development and plasticity and its effects are mediated by inhibitory (A(1), A(3)) and excitatory (A(2a), A(2b)) receptors. The role of adenosine in the synaptic activity depends mainly on a balanced activation of A(1) and A(2a) receptors which are activated by various ranges of adenosine concentrations. Herein, we investigated the expression of A(1) and A(2a) receptors and also the accumulation of cAMP in the superior colliculus at different stages of development. Furthermore, we examined the effects of an acute in vivo blockade of adenosine deaminase during the critical period when the elimination of misplaced axons/terminals takes place with a simultaneous fine tuning of terminal arbors into appropriate terminal zones. Lister Hooded rats ranging from postnatal days (PND) 0-70 were used for ontogeny studies. Our results indicate that A(1) expression in the visual layers of the superior colliculus is higher until PND 28, while A(2a) expression increases after PND 28 in a complementary developmental pattern. Accordingly, the incubation of collicular slices with 5'-N-ethylcarboxamido-adenosine, a non-specific adenosine receptor agonist, showed a significant reduction in cAMP accumulation at PND 14 and an increase in adults. For the anatomical studies, the uncrossed retinotectal projections were traced after the intraocular injection of horseradish peroxidase. One group received daily injections of an adenosine deaminase inhibitor (erythro-9(2-hydroxy-3-nonyl adenine), 10 mg/kg i.p.) between PND 10 and 13, while control groups were treated with vehicle injections (NaCl 0.9%, i.p.). We found that a short-term blockade of adenosine deaminase during the second postnatal week induced an expansion of retinotectal terminal fields in the rostrocaudal axis of the tectum. Taken together, the results suggest that a balance of purinergic A(1) and A(2a) receptors through cAMP signaling plays a pivotal role during the development of topographic order in the retinotectal pathway.

Mismatch negativity with visual-only and audiovisual speech.

The functional organization of cortical speech processing is thought to be hierarchical, increasing in complexity and proceeding from primary sensory areas centrifugally. The current study used the mismatch negativity (MMN) obtained with electrophysiology (EEG) to investigate the early latency period of visual speech processing under both visual-only (VO) and audiovisual (AV) conditions. Current density reconstruction (CDR) methods were used to model the cortical MMN generator locations. MMNs were obtained with VO and AV speech stimuli at early latencies (approximately 82-87 ms peak in time waveforms relative to the acoustic onset) and in regions of the right lateral temporal and parietal cortices. Latencies were consistent with bottom-up processing of the visible stimuli. We suggest that a visual pathway extracts phonetic cues from visible speech, and that previously reported effects of AV speech in classical early auditory areas, given later reported latencies, could be attributable to modulatory feedback from visual phonetic processing.

Overlap of nigrothalamic terminals and thalamostriatal neurons in the feline lateralis medialis-suprageniculate nucleus.

The lateralis medialis-suprageniculate nucleus (LM-Sg) of the feline posterior thalamus is a relay nucleus with a clear visuomotor function. In this study, we examined the distribution of axon terminals of the nigral afferent to the LM-Sg following injection of an anterograde tracer, biocytin, into the substantia nigra pars reticulata, and the distribution of the thalamostriatal projection neurons in the LM-Sg following the injection of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) as a retrograde tracer into the caudate nucleus. The biocytin-labeled terminal-like puncta were located in the ventromedial portion of this nucleus in such a way that most of the labeled elements took the form of swellings having boutons in places, while a minority appeared in clusters of 3-5 large terminal-like puncta. The retrograde WGA-HRP-labeled neurons were also found in the ventromedial part of the LM-Sg, and the distributions of labeled nigrothalamic axon terminals and labeled thalamostriatal projection neurons therefore overlapped in this region. The present results indicate that the nigral afferent may make synaptic contacts directly with the thalamostriatal projection neurons within the LM-Sg.

Visual attention: the thalamus at the centre?

New work shows that spatial attention modulates visual responses of single neurons in monkey thalamus, providing empirical support for a long-standing theoretical prediction that specific thalamic nuclei play a key role in controlling the spotlight of visual attention.

Morphological properties of chick retinal ganglion cells in relation to their central projections.

Morphological properties of chick retinal ganglion cells (RGCs) were studied in relation to their central projections in 23 chicks. A total of 217 RGCs were retrogradely labeled by applying a carbocyanine dye (DiI) to the thalamus and optic tectum. The labeled RGCs were classified into six groups on the basis of their somal areas, dendritic fields, and branching patterns. The dendrites of these RGCs extended horizontally in the inner plexiform layer (IPL) forming eight dendritic strata. The RGCs in each group showed certain specificities in their central projections. Group Ic predominantly projected to the tectum. Groups IIs and IIIs showed a high thalamic dominance. Groups Is and IIc were nonspecific with regard to their tectal and thalamic projections. Group IVc showed tectal-specific projections. Occurrence rates of the dendritic strata increased progressively toward the inner part of the IPL, i.e., DSs (dendritic strata) 1-4 were scantily distributed, DSs 5 and 6 were moderately distributed, and DSs 7 and 8 were the most frequently distributed. A total of 42 dendritic stratification patterns were identified, and of these, 18 patterns were common to the tectal RGCs (tec-RGCs) and thalamic RGCs (tha-RGCs). The common patterns were detected very frequently in the tec- and tha-RGCs (approximately 85%), and the dendritic strata were largely distributed in the inner part of the IPL (DSs 5-8). In contrast, the remaining 24 noncommon stratification patterns showed low occurrence rates (approximately 15%); however, these dendritic strata were widely distributed in both the outer (DSs 1-4) and inner (DSs 5-8) IPL.