The sensory thalamus and visual midbrain in mouse lemurs.

Mouse lemurs are the smallest of extant primates and are thought to resemble early primates in many ways. We provide histological descriptions of the major sensory nuclei of the dorsal thalamus and the superior colliculus (SC) of mouse lemurs (Microcebus murinus). The dorsal lateral geniculate nucleus has the six layers typical of strepsirrhine primates, with matching pairs of magnocellular, parvocellular, and koniocellular layers, one of each pair for each eye. Unlike most primates, magnocellular and parvocellular layers exhibit only small differences in cell size. All layers express vesicular glutamate transporter 2 (VGLUT2), reflecting terminations of retinal inputs, and the expression of VGLUT2 is much less dense in the koniocellular layers. Parvalbumin is densely expressed in all layers, while SMI-32 is densely expressed only in the magnocellular layers. The adjoining pulvinar complex has a posterior nucleus with strong VGLUT2 expression, reflecting terminations from the SC. The SC is laminated with dense expression of VGLUT2 in the upper superficial gray layer, reflecting terminations from the retina. The ventral (MGNv), medial, and dorsal divisions of the medial geniculate complex are only moderately differentiated, although patches of dense VGLUT2 expression are found along the outer border of MGNv. The ventroposterior nucleus has darkly stained cells in Nissl stained sections, and narrow septa separating patchy regions of dense VGLUT2 expression that likely represent different body parts. Overall, these structures resemble those in other strepsirrhine primates, although they are smaller, with the sensory nuclei appearing to occupy proportionately more of the dorsal thalamus than in larger primates.

Architectonic characteristics of the visual thalamus and superior colliculus in titi monkeys.

Titi monkeys are arboreal, diurnal New World monkeys whose ancestors were the first surviving branch of the New World radiation. In the current study, we use cytoarchitectonic and immunohistochemical characteristics to compare titi monkey subcortical structures associated with visual processing with those of other well-studied primates. Our goal was to appreciate features that are similar across all New World monkeys, and primates in general, versus those features that are unique to titi monkeys and other primate taxa. We examined tissue stained for Nissl substance, cytochrome oxidase (CO), acetylcholinesterase (AChE), calbindin (Cb), parvalbumin (Pv), and vesicular glutamate transporter 2 (VGLUT2) to characterize the superior colliculus, lateral geniculate nucleus, and visual pulvinar. This is the first study to characterize VGLUT2 in multiple subcortical structures of any New World monkey. Our results from tissue processed for VGLUT2, in combination with other histological stains, revealed distinct features of subcortical structures that are similar to other primates, but also some features that are slightly modified compared to other New World monkeys and other primates. These included subdivisions of the inferior pulvinar, sublamina within the stratum griseum superficiale (SGS) of the superior colliculus, and specific koniocellular layers within the lateral geniculate nucleus. Compared to other New World primates, many features of the subcortical structures that we examined in titi monkeys were most similar to those in owl monkeys and marmosets, with the lateral geniculate nucleus consisting of two main parvocellular layers and two magnocellular layers separated by interlaminar zones or koniocellular layers.

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.

The Zona Incerta Regulates Communication between the Superior Colliculus and the Posteromedial Thalamus: Implications for Thalamic Interactions with the Dorsolateral Striatum.

There is uncertainty concerning the circuit connections by which the superior colliculus interacts with the basal ganglia. To address this issue, anterograde and retrograde tracers were placed, respectively, into the superior colliculus and globus pallidus of Sprague-Dawley rats. In this two-tracer experiment, the projections from the superior colliculus terminated densely in the ventral zona incerta (ZIv), but did not overlap the labeled neurons observed in the subthalamic nucleus. In cases in which anterograde and retrograde tracers were placed, respectively, in sensory-responsive sites in the superior colliculus and posteromedial (POm) thalamus, the labeled projections from superior colliculus innervated the ZIv regions that contained the labeled neurons that project to POm. We also confirmed this colliculo-incertal-POm pathway by depositing a mixture of retrograde and anterograde tracers at focal sites in ZIv to reveal retrogradely labeled neurons in superior colliculus and anterogradely labeled terminals in POm. When combined with retrograde tracer injections in POm, immunohistochemical processing proved that most ZIv projections to POm are GABAergic. Consistent with these findings, direct stimulation of superior colliculus evoked neuronal excitation in ZIv and caused inhibition of spontaneous activity in POm. Collectively, these results indicate that superior colliculus can activate the inhibitory projections from ZIv to the POm. This is significant because it suggests that the superior colliculus could suppress the interactions between POm and the dorsolateral striatum, presumably to halt ongoing behaviors so that more adaptive motor actions are selected in response to unexpected sensory events. SIGNIFICANCE STATEMENT: By demonstrating that the zona incerta regulates communication between the superior colliculus and the posteromedial thalamus, we have uncovered a circuit that partly explains the behavioral changes that occur in response to unexpected sensory stimuli. Furthermore, this circuit could explain why deep brain stimulation of the zona incerta is beneficial to patients who suffer from Parkinson's disease.

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.

The superior colliculus of the ferret: cortical afferents and efferent connections to dorsal thalamus.

By injecting both biotinylated and fluorescent dextran amines into the superior colliculus of the ferret we traced its afferent connections from the cerebral cortex and its projections to nuclei of the dorsal thalamus. All visual and auditory cortical areas had retrogradely labelled layer 5 pyramidal neurons projecting to the superior colliculus, with the highest density in areas 18 and 21. Secondary somatosensory and motor cortical regions also projected to the superior colliculus. No retrograde labelling was observed in primary somatosensory, primary motor or prefrontal cortex. All visual dorsal thalamic nuclei received connections from the superior colliculus. Within the LGN, lamina C and the medial interlaminar nucleus (MIN) received dense afferents terminating with large labelled boutons. Within the lateral posterior nucleus (LP) a distinct band of moderately dense small, labelled boutons was observed, and within the pulvinar a broader and less dense region of small bouton labelling was observed. For the most part these connections are similar to those seen in the cat and other mammals, however, specific comparisons appear to delineate potential evolutionary trends related to complexity of the visual system.

Topography and physiology of ascending streams in the auditory tectothalamic pathway.

Auditory information is relayed from the cochlea along parallel pathways and reaches the inferior colliculus (IC) and the medial geniculate body (MGB) en route to the cortex. Although the ascending tectothalamic pathway to the ventral division of the MGB is regarded as a high-fidelity information-bearing channel, the roles of the pathways to the dorsal and medial divisions are more opaque. Here, we show fundamental differences between these ascending pathways using an in vitro slice preparation. Using photostimulation, we found three main patterns of input (excitatory, inhibitory, and mixed) that differed in each pathway. Furthermore, electrical stimulation of the central nucleus of the IC evoked a depressing response in the MGB with no metabotropic glutamate (mGlu) receptor component, whereas stimulation of the lateral cortex of the IC evoked a facilitating response with an mGlu receptor component. These data suggest that the ascending tectothalamic pathways are functionally distinct from one another.

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.

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.

Long-term astroglial reaction and neuronal plasticity in the subcortical visual pathways after a complete ablation of telencephalon in pigeons (Columba livia).

This paper analyzes the astroglial and neuronal responses in subtelencephalic structures, following a bilateral ablation of the telencephalon in the Columba livia pigeons. Control birds received a sham operation. Four months later the birds were sacrificed and their brains processed for glial fibrillary acid protein (GFAP) and neurofilament immunohistochemistry, markers for astrocytes and neurons, respectively. Computer-assisted image analysis was employed for quantification of the immunoreactive labeling in the nucleus rotundus (N.Rt) and the optic tectum (OT) of the birds. An increased number of GFAP immunoreactive astrocytes were found in several subregions of the N.Rt (p< .001), as well as in layers 1, 2cd, 3, and 6 of the OT (p< .001) of the lesioned animals. Neurofilament immunoreactivity decreased massively in the entire N.Rt of the lesioned birds; however, remaining neurons with healthy aspect showing large cytoplasm and ramified branches were detected mainly in the periphery of the nucleus. In view of the recently described paracrine neurotrophic properties of the activated astrocytes, the data of the present study may suggest a long-lasting neuroglial interaction in regions of the lesioned bird brain far from injury. Such events may trigger neuronal plasticity in remaining brain structures that may lead spontaneous behavior recovery as the one promoted here even after a massive injury.

Corollary discharge circuits for saccadic modulation of the pigeon visual system.

A saccadic eye movement causes a variety of transient perceptual sequelae that might be the results of corollary discharge. Here we describe the neural circuits for saccadic corollary discharge that modulates activity throughout the pigeon visual system. Saccades in pigeons caused inhibition that was mediated by corollary discharge followed by enhancement of firing activity in the telencephalic hyperpallium, visual thalamus and pretectal nucleus lentiformis mesencephali (nLM) with opposite responses in the accessory optic nucleus (nBOR). Inactivation of thalamic neurons eliminated saccadic responses in telencephalic neurons, and inactivation of both the nLM and the nBOR abolished saccadic responses in thalamic neurons. Saccade-related omnipause neurons in the brainstem raphe complex inhibited the nBOR and excited the nLM, whereas inactivation of raphe neurons eliminated saccadic responses in both optokinetic and thalamic neurons. It seems that saccadic responses in telencephalic neurons are generated by corollary discharge signals from brainstem neurons that are transmitted through optokinetic and thalamic neurons. These signals might have important roles in visual perception.

Transcriptome changes associated with instructed learning in the barn owl auditory localization pathway.

Owls reared wearing prismatic spectacles learn to make adaptive orienting movements. This instructed learning depends on re-calibration of the midbrain auditory space map, which in turn involves the formation of new synapses. Here we investigated whether these processes are associated with differential gene expression, using longSAGE. Newly fledged owls were reared for 8-36 days with prism or control lenses at which time the extent of learning was quantified by electrophysiological mapping. Transciptome profiles were obtained from the inferior colliculus (IC), the major site of synaptic plasticity, and the optic tectum (OT), which provides an instructive signal that controls the direction and extent of plasticity. Twenty-two differentially expressed sequence tags were identified in IC and 36 in OT, out of more than 35,000 unique tags. Of these, only four were regulated in both structures. These results indicate that regulation of two largely independent gene clusters is associated with synaptic remodeling (in IC) and generation of the instructive signal (in OT). Real-time PCR data confirmed the changes for two transcripts, ubiquitin/polyubiquitin and tyrosine 3-monooxgenase/tryotophan 5-monooxygenase activation protein, theta subunit (YWHAQ; also referred to as 14-3-3 protein). Ubiquitin was downregulated in IC, consistent with a model in which protein degradation pathways act as an inhibitory constraint on synaptogenesis. YWHAQ was up-regulated in OT, indicating a role in the synthesis or delivery of instructive information. In total, our results provide a path towards unraveling molecular cascades that link naturalistic experience with synaptic remodeling and, ultimately, with the expression of learned behavior.

DC electrical stimulation of the pretectal thalamus and its effects on the feeding behavior of the toad (Bufo bufo).

The feeding motivation of the common European common toad (Bufo bufo) can be quantified by the feeding sequence of arousal-orientation-approach-fixate-snap. Previous work has found that the optic tectum is an important structure responsible for the mediation of feeding behaviors, and combined electrical and visual stimulation of the optic tectum was found to increase the animals feeding behaviors. However, the pretectal thalamus has an inhibitory influence upon the optic tectum and its lesion results in disinhibited feeding behaviors. This suggests that feeding behavior of anurans is also subject to influence from the pretectal thalamus. Previous studies involving the application of DC stimulation to brain tissue has generated slow potential shifts and these shifts have been implicated in the modulation of the neural mechanisms associated with behavior. The current study investigated the application of DC stimulation to the diencephalon surface dorsal to the lateral posterodorsal pretectal thalamic nucleus in Bufo bufo, in order to assess effects on feeding motivation. The application of DC stimulation increased the incidence of avoidance behaviors to a visual prey stimulus while reducing the prey catching behavior component of approach, suggesting that the DC current applied to the pretectum increased the inhibition upon the feeding elements of the optic tectum. This can be explained by the generation of slow potential shifts.

Present concepts of oculomotor organization.

This chapter gives an introduction to the oculomotor system, thus providing a framework for the subsequent chapters. This chapter describes the characteristics, and outlines the structures involved, of the five basic types of eye movements, for gaze holding ("neural integrator") and eye movements in three dimensions (Listing's law, pulleys).

Nucleus prepositus.

The cytoarchitecture and the histochemistry of nucleus prepositus hypoglossi and its afferent and efferent connections to oculomotor structures are described. The functional significance of the afferent connections of the nucleus is discussed in terms of current knowledge of the firing behavior of prepositus neurons in alert animals. The efferent connections of the nucleus and the results of lesion experiments suggest that it plays a role in a variety of functions related to the control of gaze.

The mammalian superior colliculus: laminar structure and connections.

The superior colliculus is a laminated midbrain structure that acts as one of the centers organizing gaze movements. This review will concentrate on sensory and motor inputs to the superior colliculus, on its internal circuitry, and on its connections with other brainstem gaze centers, as well as its extensive outputs to those structures with which it is reciprocally connected. This will be done in the context of its laminar arrangement. Specifically, the superficial layers receive direct retinal input, and are primarily visual sensory in nature. They project upon the visual thalamus and pretectum to influence visual perception. These visual layers also project upon the deeper layers, which are both multimodal, and premotor in nature. Thus, the deep layers receive input from both somatosensory and auditory sources, as well as from the basal ganglia and cerebellum. Sensory, association, and motor areas of cerebral cortex provide another major source of collicular input, particularly in more encephalized species. For example, visual sensory cortex terminates superficially, while the eye fields target the deeper layers. The deeper layers are themselves the source of a major projection by way of the predorsal bundle which contributes collicular target information to the brainstem structures containing gaze-related burst neurons, and the spinal cord and medullary reticular formation regions that produce head turning.

The pretectum: connections and oculomotor-related roles.

Research over the past two decades in mammals, especially primates, has greatly improved our understanding of the afferent and efferent connections of two retinorecipient pretectal nuclei, the nucleus of the optic tract (NOT) and the pretectal olivary nucleus (PON). Functional studies of these two nuclei have further elucidated some of the roles that they play both in oculomotor control and in relaying oculomotor-related signals to visual relay nuclei. Therefore, following a brief overview of the anatomy and retinal projections to the entire mammalian pretectum, the connections and potential roles of the NOT and the PON are considered in detail. Data on the specific connections of the NOT are combined with data from single-unit recording, microstimulation, and lesion studies to show that this nucleus plays critical roles in optokinetic nystagmus, short-latency ocular following, smooth pursuit eye movements, and adaptation of the gain of the horizontal vestibulo-ocular reflex. Comparable data for the PON show that this nucleus plays critical roles in the pupillary light reflex, light-evoked blinks, rapid eye movement sleep triggering, and modulating subcortical nuclei involved in circadian rhythms.

Cortico-cortical networks and cortico-subcortical loops for the higher control of eye movements.

There are multiple distinct regions, or eye fields, in the cerebral cortex that contribute directly to the initiation and control of voluntary eye movements. We concentrate on six of these: the frontal eye field, parietal eye field, supplementary eye field, middle superior temporal area, prefrontal eye field, and area 7 m (precuneus in humans). In each of these regions: (1) there is neural activity closely related to eye movements; (2) electrical microstimulation produces or modifies eye movements; (3) surgical lesions or chemical inactivation impairs eye movements; (4) there are direct neural projections to major structures in the brainstem oculomotor system; and (5) increased activity is observed during eye movement tasks in functional magnetic resonance imaging or positron emission tomography experiments in humans. Each of these eye fields is reciprocally connected with the other eye fields, and each receives visual information directly from visual association cortex. Each eye field has distinct subregions that are concerned with either saccadic or pursuit eye movements. The saccadic subregions are preferentially interconnected with other saccade subregions and the pursuit subregions are preferentially interconnected with other pursuit subregions. Current evidence strongly supports the proposal that there are parallel cortico-cortical networks that control purposeful saccadic and pursuit eye movements, and that the activity in those networks is modulated by feedback information, via the thalamus, from the superior colliculus, basal ganglia, and cerebellum.