Neurexin1⍺ differentially regulates synaptic efficacy within striatal circuits.

Mutations in genes essential for synaptic function, such as the presynaptic adhesion molecule Neurexin1α (Nrxn1α), are strongly implicated in neuropsychiatric pathophysiology. As the input nucleus of the basal ganglia, the striatum integrates diverse excitatory projections governing cognitive and motor control, and its impairment may represent a recurrent pathway to disease. Here, we test the functional relevance of Nrxn1α in striatal circuits by employing optogenetic-mediated afferent recruitment of dorsal prefrontal cortical (dPFC) and parafascicular thalamic connections onto dorsomedial striatal (DMS) spiny projection neurons (SPNs). For dPFC-DMS circuits, we find decreased synaptic strength specifically onto indirect pathway SPNs in both Nrxn1α+/- and Nrxn1α-/- mice, driven by reductions in neurotransmitter release. In contrast, thalamic excitatory inputs to DMS exhibit relatively normal excitatory synaptic strength despite changes in synaptic N-methyl-D-aspartate receptor (NMDAR) content. These findings suggest that dysregulation of Nrxn1α modulates striatal function in an input- and target-specific manner.

Olfaction in Lamprey Pallium Revisited-Dual Projections of Mitral and Tufted Cells.

The presence of two separate afferent channels from the olfactory glomeruli to different targets in the brain is unravelled in the lamprey. The mitral-like cells send axonal projections directly to the piriform cortex in the ventral part of pallium, whereas the smaller tufted-like cells project separately and exclusively to a relay nucleus called the dorsomedial telencephalic nucleus (dmtn). This nucleus, located at the interface between the olfactory bulb and pallium, in turn projects to a circumscribed area in the anteromedial, ventral part of pallium. The tufted-like cells are activated with short latency from the olfactory nerve and terminate with mossy fibers on the dmtn cells, wherein they elicit large unitary excitatory postsynaptic potentials (EPSPs). In all synapses along this tufted-like cell pathway, there is no concurrent inhibition, in contrast to the mitral-like cell pathway. This is similar to recent findings in rodents establishing two separate exclusive projection patterns, suggesting an evolutionarily conserved organization.

Afferent and efferent connections of the nucleus prethalamicus in the yellowfin goby Acanthogobius flavimanus.

The nucleus prethalamicus (PTh) receives fibers from the optic tectum and then projects to the dorsal telencephalon in the yellowfin goby Acanthogobius flavimanus. However, it remained unclear whether the PTh is a visual relay nucleus, because the optic tectum receives not only visual but also other sensory modalities. Furthermore, precise telencephalic regions receiving prethalamic input remained unknown in the goby. We therefore investigated the full set of afferent and efferent connections of the PTh by direct tracer injections into the nucleus. Injections into the PTh labeled cells in the optic tectum, ventromedial thalamic nucleus, central and medial parts of the dorsal telencephalon, and caudal lobe of the cerebellum. We found that the somata of most tecto-prethalamic neurons are present in the stratum periventriculare. Their dendrites ascend to reach the major retinorecipient layers of the tectum. The PTh is composed of two subnuclei (medial and lateral) and topographic organization was appreciated only for tectal projections to the lateral subnucleus (PTh-l), which also receives sparse retinal projections. In contrast, the medial subnucleus receives fibers only from the medial tectum. We found that the PTh projects to nine subregions in the dorsal telencephalon and four in the ventral telencephalon. Furthermore, cerebellar injections revealed that cerebello-prethalamic fibers cross the midline twice to innervate the PTh-l on both sides. The present study is the first detailed report on the full set of the connections of PTh, which suggests that the PTh relays visual information from the optic tectum to the telencephalon.

Circuit-Specific Plasticity of Callosal Inputs Underlies Cortical Takeover.

Injury induces synaptic, circuit, and systems reorganization. After unilateral amputation or stroke, this functional loss disrupts the interhemispheric interaction between intact and deprived somatomotor cortices to recruit deprived cortex in response to intact limb stimulation. This recruitment has been implicated in enhanced intact sensory function. In other patients, maladaptive consequences such as phantom limb pain can occur. We used unilateral whisker denervation in male and female mice to detect circuitry alterations underlying interhemispheric cortical reorganization. Enhanced synaptic strength from the intact cortex via the corpus callosum (CC) onto deep neurons in deprived primary somatosensory barrel cortex (S1BC) has previously been detected. It was hypothesized that specificity in this plasticity may depend on to which area these neurons projected. Increased connectivity to somatomotor areas such as contralateral S1BC, primary motor cortex (M1) and secondary somatosensory cortex (S2) may underlie beneficial adaptations, while increased connectivity to pain areas like anterior cingulate cortex (ACC) might underlie maladaptive pain phenotypes. Neurons from the deprived S1BC that project to intact S1BC were hyperexcitable, had stronger responses and reduced inhibitory input to CC stimulation. M1-projecting neurons also showed increases in excitability and CC input strength that was offset with enhanced inhibition. S2 and ACC-projecting neurons showed no changes in excitability or CC input. These results demonstrate that subgroups of output neurons undergo dramatic and specific plasticity after peripheral injury. The changes in S1BC-projecting neurons likely underlie enhanced reciprocal connectivity of S1BC after unilateral deprivation consistent with the model that interhemispheric takeover supports intact whisker processing.SIGNIFICANCE STATEMENT Amputation, peripheral injury, and stroke patients experience widespread alterations in neural activity after sensory loss. A hallmark of this reorganization is the recruitment of deprived cortical space which likely aids processing and thus enhances performance on intact sensory systems. Conversely, this recruitment of deprived cortical space has been hypothesized to underlie phenotypes like phantom limb pain and hinder recovery. A mouse model of unilateral denervation detected remarkable specificity in alterations in the somatomotor circuit. These changes underlie increased reciprocal connectivity between intact and deprived cortical hemispheres. This increased connectivity may help explain the enhanced intact sensory processing detected in humans.

A subset of broadly responsive Type III taste cells contribute to the detection of bitter, sweet and umami stimuli.

Taste receptor cells use multiple signaling pathways to detect chemicals in potential food items. These cells are functionally grouped into different types: Type I cells act as support cells and have glial-like properties; Type II cells detect bitter, sweet, and umami taste stimuli; and Type III cells detect sour and salty stimuli. We have identified a new population of taste cells that are broadly tuned to multiple taste stimuli including bitter, sweet, sour, and umami. The goal of this study was to characterize these broadly responsive (BR) taste cells. We used an IP3R3-KO mouse (does not release calcium (Ca2+) from internal stores in Type II cells when stimulated with bitter, sweet, or umami stimuli) to characterize the BR cells without any potentially confounding input from Type II cells. Using live cell Ca2+ imaging in isolated taste cells from the IP3R3-KO mouse, we found that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLCß signaling pathway to respond to bitter, sweet, and umami stimuli. Unlike Type II cells, individual BR cells are broadly tuned and respond to multiple stimuli across different taste modalities. Live cell imaging in a PLCß3-KO mouse confirmed that BR cells use this signaling pathway to respond to bitter, sweet, and umami stimuli. Short term behavioral assays revealed that BR cells make significant contributions to taste driven behaviors and found that loss of either PLCß3 in BR cells or IP3R3 in Type II cells caused similar behavioral deficits to bitter, sweet, and umami stimuli. Analysis of c-Fos activity in the nucleus of the solitary tract (NTS) also demonstrated that functional Type II and BR cells are required for normal stimulus induced expression.

The Parabrachial Nucleus Directly Channels Spinal Nociceptive Signals to the Intralaminar Thalamic Nuclei, but Not the Amygdala.

The parabrachial nucleus (PBN) is one of the major targets of spinal projection neurons and plays important roles in pain. However, the architecture of the spinoparabrachial pathway underlying its functional role in nociceptive information processing remains elusive. Here, we report that the PBN directly relays nociceptive signals from the spinal cord to the intralaminar thalamic nuclei (ILN). We demonstrate that the spinal cord connects with the PBN in a bilateral manner and that the ipsilateral spinoparabrachial pathway is critical for nocifensive behavior. We identify Tacr1-expressing neurons as the major neuronal subtype in the PBN that receives direct spinal input and show that these neurons are critical for processing nociceptive information. Furthermore, PBN neurons receiving spinal input form functional monosynaptic excitatory connections with neurons in the ILN, but not the amygdala. Together, our results delineate the neural circuit underlying nocifensive behavior, providing crucial insight into the circuit mechanism underlying nociceptive information processing.

Thalamic afferents emphasize the different functions of macaque precuneate areas.

We studied the thalamic afferents to cortical areas in the precuneus using injections of retrograde fluorescent neuronal tracers in four male macaques (Macaca fascicularis). Six injections were within the limits of cytoarchitectural area PGm, one in area 31 and one in area PEci. Precuneate areas shared strong input from the posterior thalamus (lateral posterior nucleus and pulvinar complex) and moderate input from the medial, lateral, and intralaminar thalamic regions. Area PGm received strong connections from the subdivisions of the pulvinar linked to association and visual function (the medial and lateral nuclei), whereas areas 31 and PEci received afferents from the oral division of the pulvinar. All three cytoarchitectural areas also received input from subdivisions of the lateral thalamus linked to motor function (ventral lateral and ventral anterior nuclei), with area PEci receiving additional input from a subdivision linked to somatosensory function (ventral posterior lateral nucleus). Finally, only PGm received substantial limbic association afferents, mainly via the lateral dorsal nucleus. These results indicate that area PGm integrates information from visual association, motor and limbic regions of the thalamus, in line with a hypothesized role in spatial cognition, including navigation. By comparison, dorsal precuneate areas (31 and PEci) are more involved in sensorimotor functions, being akin to adjacent areas of the dorsal parietal cortex.

Afferent connections of the thalamic nucleus reuniens in the mouse.

The nucleus reuniens (RE) is part of the midline thalamus and one of the major sources of thalamic inputs to the hippocampal formation and the medial prefrontal cortex. However, it not only sends strong efferents to these areas but is also heavily innervated by both brain regions. Based on its connectivity and supported by functional studies the RE has been suggested to represent a major hub in reciprocal hippocampal-prefrontal communication. Indeed, inactivation studies have demonstrated that this nucleus is particularly important for cognitive behaviors which depend on prefrontal-hippocampal communication, such as working memory or memory consolidation. However, besides its central role in mediating hippocampal-prefrontal communication, the RE is target of a multitude of other cortical and subcortical afferents, which likely modulate its function. So far, however, studies that have systematically investigated the afferents of the RE have only been performed in rats. Because of the unique role of the mouse as a genetically accessible model system for mammalian brain circuit analysis we have mapped the afferent connectivity of the mouse RE using retrograde Fluoro-Gold tracing. Comparison with similar data from rats indicated a very high level of similarity in prefrontal and hippocampal afferents but some differences in afferent connectivity with other brain regions. In particular, our results suggest interspecies differences regarding the integration of the RE in circuits of fear, aversion, and defense.

Sour Sensing from the Tongue to the Brain.

The ability to sense sour provides an important sensory signal to prevent the ingestion of unripe, spoiled, or fermented foods. Taste and somatosensory receptors in the oral cavity trigger aversive behaviors in response to acid stimuli. Here, we show that the ion channel Otopetrin-1, a proton-selective channel normally involved in the sensation of gravity in the vestibular system, is essential for sour sensing in the taste system. We demonstrate that knockout of Otop1 eliminates acid responses from sour-sensing taste receptor cells (TRCs). In addition, we show that mice engineered to express otopetrin-1 in sweet TRCs have sweet cells that also respond to sour stimuli. Next, we genetically identified the taste ganglion neurons mediating each of the five basic taste qualities and demonstrate that sour taste uses its own dedicated labeled line from TRCs in the tongue to finely tuned taste neurons in the brain to trigger aversive behaviors.

Afferent neuropeptide Y projections to the ventral tegmental area in normal-weight male Wistar rats.

The hypothalamic neuropeptide Y (NPY) circuitry is a key regulator of feeding behavior. NPY also acts in the mesolimbic dopaminergic circuitry, where it can increase motivational aspects of feeding behavior through effects on dopamine output in the nucleus accumbens (NAc) and on neurotransmission in the ventral tegmental area (VTA). Endogenous NPY in the NAc originates from local interneurons and afferent projections from the hypothalamic arcuate nucleus (Arc). However, the origin of endogenous NPY in the VTA is unknown. We determined, in normal-weight male Wistar rats, if the source of VTA NPY is local, and/or whether it is derived from VTA-projecting neurons. Immunocytochemistry, in situ hybridization and RT-qPCR were utilized, when appropriate in combination with colchicine treatment or 24 hr fasting, to assess NPY/Npy expression locally in the VTA. Retrograde tracing using cholera toxin beta (CTB) in the VTA, fluorescent immunocytochemistry and confocal microscopy were used to determine NPY-immunoreactive afferents to the VTA. NPY in the VTA was observed in fibers, but not following colchicine pretreatment. No NPY- or Npy-expressing cell bodies were observed in the VTA. Fasting for 24 hr, which increased Npy expression in the Arc, failed to induce Npy expression in the VTA. Double-labeling with CTB and NPY was observed in the Arc and in the ventrolateral medulla. Thus, VTA NPY originates from the hypothalamic Arc and the ventrolateral medulla of the brainstem in normal-weight male Wistar rats. These afferent connections link hypothalamic and brainstem processing of physiologic state to VTA-driven motivational behavior.

Central connections of the trigeminal motor command system in the weakly electric Elephantnose fish (Gnathonemus petersii).

The highly mobile chin appendage of Gnathonemus petersii, the Schnauzenorgan, is used to actively probe the environment and is known to be a fovea of the electrosensory system. It receives an important innervation from both the trigeminal sensory and motor systems. However, little is known about the premotor control pathways that coordinate the movements of the Schnauzenorgan, or about central pathways originating from the trigeminal motor nucleus. The present study focuses on the central connections of the trigeminal motor system to elucidate premotor centers controlling Schnauzenorgan movements, with particular interest in the possible connections between the electrosensory and trigeminal systems. Neurotracer injections into the trigeminal motor nucleus revealed bilateral, reciprocal connections between the two trigeminal motor nuclei and between the trigeminal sensory and motor nuclei by bilateral labeling of cells and terminals. Prominent afferent input to the trigeminal motor nucleus originates from the nucleus lateralis valvulae, the nucleus dorsalis mesencephali, the cerebellar corpus C1, the reticular formation, and the Raphe nuclei. Retrogradely labeled cells were also observed in the central pretectal nucleus, the dorsal anterior pretectal nucleus, the tectum, the ventroposterior nucleus of the torus semicircularis, the gustatory sensory and motor nuclei, and in the hypothalamus. Labeled terminals, but not cell bodies, were observed in the nucleus lateralis valvulae and the reticular formation. No direct connections were found between the electrosensory system and the V motor nucleus but the central connections identified would provide several multisynaptic pathways linking these two systems, including possible efference copy and corollary discharge mechanisms.

Thalamocortical Afferents Innervate the Cortical Subplate much Earlier in Development in Primate than in Rodent.

The current model, based on rodent data, proposes that thalamocortical afferents (TCA) innervate the subplate towards the end of cortical neurogenesis. This implies that the laminar identity of cortical neurons is specified by intrinsic instructions rather than information of thalamic origin. In order to determine whether this mechanism is conserved in the primates, we examined the growth of thalamocortical (TCA) and corticofugal afferents in early human and monkey fetal development. In the human, TCA, identified by secretagogin, calbindin, and ROBO1 immunoreactivity, were observed in the internal capsule of the ventral telencephalon as early as 7-7.5 PCW, crossing the pallial/subpallial boundary (PSB) by 8 PCW before the calretinin immunoreactive corticofugal fibers do. Furthermore, TCA were observed to be passing through the intermediate zone and innervating the presubplate of the dorsolateral cortex, and already by 10-12 PCW TCAs were occupying much of the cortex. Observations at equivalent stages in the marmoset confirmed that this pattern is conserved across primates. Therefore, our results demonstrate that in primates, TCAs innervate the cortical presubplate at earlier stages than previously demonstrated by acetylcholinesterase histochemistry, suggesting that pioneer thalamic afferents may contribute to early cortical circuitry that can participate in defining cortical neuron phenotypes.

Differential innervation within a transverse plane of spinal gray matter by sensorimotor cortices, with special reference to the somatosensory cortices.

The corticospinal (CS) neurons projecting to the cervical cord distribute not only in motor-related cortical areas, but also in somatosensory areas, including the primary somatosensory cortex (S1). The exact functions of these widely distributed CS neurons are largely unknown, however. In this study, we injected mice with adeno-associated virus encoding membrane-binding fluorescent proteins to investigate the distribution of axons from CS neurons in different regions within a broad cortical area. We found that CS axons from the primary motor cortex (M1), the rostral part of S1 (S1r), and the caudal part of S1 (S1c) differentially project to specific compartments within the spinal gray matter of the seventh cervical cord segment: (a) M1 projects mainly to intermediate and ventral areas, (b) S1r to the mediodorsal area, and (c) S1c to the dorsolateral area. We also found that the projection from S1r, which corresponds to the forelimb area, largely overlaps the cutaneous afferent terminals from the forepaw (hand) in the dorsal horn, and we detected a similar relation between S1c and the trunk. Our findings suggest the existence of considerably fine somatotopic compartments within the dorsal horn that process somatosensation and descending information, which is provided mainly by S1 CS neurons and contribute to delicate control of sensory information in generation of movement.

Cortical Afferents of Area 10 in Cebus Monkeys: Implications for the Evolution of the Frontal Pole.

Area 10, located in the frontal pole, is a unique specialization of the primate cortex. We studied the cortical connections of area 10 in the New World Cebus monkey, using injections of retrograde tracers in different parts of this area. We found that injections throughout area 10 labeled neurons in a consistent set of areas in the dorsolateral, ventrolateral, orbital, and medial parts of the frontal cortex, superior temporal association cortex, and posterior cingulate/retrosplenial region. However, sites on the midline surface of area 10 received more substantial projections from the temporal lobe, including clear auditory connections, whereas those in more lateral parts received >90% of their afferents from other frontal areas. This difference in anatomical connectivity reflects functional connectivity findings in the human brain. The pattern of connections in Cebus is very similar to that observed in the Old World macaque monkey, despite >40 million years of evolutionary separation, but lacks some of the connections reported in the more closely related but smaller marmoset monkey. These findings suggest that the clearer segregation observed in the human frontal pole reflects regional differences already present in early simian primates, and that overall brain mass influences the pattern of cortico-cortical connectivity.

Somatotopic organization of central arbors from nociceptive afferents develops independently of their intact peripheral target innervation.

Functionally important regions of sensory maps are overrepresented in the sensory pathways and cortex, but the underlying developmental mechanisms are not clear. In the spinal cord dorsal horn (DH), we recently showed that paw innervating Mrgprd+ nonpeptidergic nociceptors display distinctive central arbor morphologies that well correlate with increased synapse transmission efficiency and heightened sensitivity of distal limb skin. Given that peripheral and central arbor formation of Mrgprd+ neurons co-occurs around the time of birth, we tested whether peripheral cues from different skin areas and/or postnatal reorganization mechanisms could instruct this somatotopic difference among central arbors. We found that, while terminal outgrowth/refinement occurs during early postnatal development in both the skin and the DH, postnatal refinement of central terminals precedes that of peripheral terminals. Furthermore, we used single-cell ablation of Ret to genetically disrupt epidermal innervation of Mrgprd+ neurons and revealed that the somatotopic difference among their central arbors was unaffected by this manipulation. Finally, we saw that region-specific Mrgprd+ central terminal arbors are present from the earliest postnatal stages, before skin terminals are evident. In summary, we find that region-specific organization of Mrgprd+ neuron central arbors is present shortly after initial central terminal formation, which likely develops independently of peripheral target innervation. Our data suggest that either cell-intrinsic and/or DH prepatterning mechanisms are likely to establish this somatotopic difference.

The greater occipital nerve and its spinal and brainstem afferent projections: A stereological and tract-tracing study in the rat.

The neuromodulation of the greater occipital nerve (GON) has proved effective to treat chronic refractory neurovascular headaches, in particular migraine and cluster headache. Moreover, animal studies have shown convergence of cervical and trigeminal afferents on the same territories of the upper cervical and lower medullary dorsal horn (DH), the so-called trigeminocervical complex (TCC), and recent studies in rat models of migraine and craniofacial neuropathy have shown that GON block or stimulation alter nociceptive processing in TCC. The present study examines in detail the anatomy of GON and its central projections in the rat applying different tracers to the nerve and quantifying its ultrastructure, the ganglion neurons subserving GON, and their innervation territories in the spinal cord and brainstem. With considerable intersubject variability in size, GON contains on average 900 myelinated and 3,300 unmyelinated axons, more than 90% of which emerge from C2 ganglion neurons. Unmyelinated afferents from GON innervates exclusively laminae I-II of the lateral DH, mostly extending along segments C2-3 . Myelinated fibers distribute mainly in laminae I and III-V of the lateral DH between C1 and C6 and, with different terminal patterns, in medial parts of the DH at upper cervical segments, and ventrolateral rostral cuneate, paratrigeminal, and marginal part of the spinal caudal and interpolar nuclei. Sparse projections also appear in other locations nearby. These findings will help to better understand the bases of sensory convergence on spinomedullary systems, a critical pathophysiological factor for pain referral and spread in severe painful craniofacial disorders.

A single GABA neuron receives contacts from myelinated primary afferents of two adjacent peripheral nerves. A possible role in neuropathic pain.

GAD67-EGFP mice were used in a series of experiments to provide anatomical evidence for the role of the reduction in myelinated primary afferent input to GABA spinal neurons in the production of neuropathic pain following peripheral L5 nerve injury. First, we confirmed that L5 injury in these mice produced mechanical and thermal hyperalgesia in the ipsilateral foot. Second, we injected a mixture of cholera toxin subunit-B (CTb) and isolectin B4 (IB4) in the sciatic nerve to selectively label its myelinated and unmyelinated primary afferents. Results showed that primary afferents of sciatic nerve extend from L2-L6 spinal segments. Third, we determined the central terminations of myelinated primary afferents of L4 and L5 spinal nerves following CTb injection in either nerve. The myelinated primary afferents of both nerves terminated in the corresponding and two to three rostral spinal segments with some fibers descending to terminate in the segment caudal to the level at which they entered indicating an intermingling of their terminals at the dorsal horn of the spinal cord. Fourthly, we injected CTb in L5 nerve and CTb HRP-conjugate in L4 nerve. Confocal microscopy and subsequent image analyses showed that individual EGFP-labeled neurons in L4 segment receive myelinated primary afferent contacts from both L4 and L5 nerves. Eliminating inputs from L5 nerve following its injury would result in less involvement of spinal GABA neurons which would very likely initiate neuronal sensitization in L4 segment. This could lead to the development of hyperalgesia in response to the stimulation of the adjacent uninjured L4 nerve.

Stereological analysis of the rhesus monkey entorhinal cortex.

The entorhinal cortex is a prominent structure of the medial temporal lobe, which plays a pivotal role in the interaction between the neocortex and the hippocampal formation in support of declarative and spatial memory functions. We implemented design-based stereological techniques to provide estimates of neuron numbers, neuronal soma size, and volume of different layers and subdivisions of the entorhinal cortex in adult rhesus monkeys (Macaca mulatta; 5-9 years of age). These data corroborate the structural differences between different subdivisions of the entorhinal cortex, which were shown in previous connectional and cytoarchitectonic studies. In particular, differences in the number of neurons contributing to distinct afferent and efferent hippocampal pathways suggest not only that different types of information may be more or less segregated between caudal and rostral subdivisions, but also, and perhaps most importantly, that the nature of the interaction between the entorhinal cortex and the rest of the hippocampal formation may vary between different subdivisions. We compare our quantitative data in monkeys with previously published stereological data for the rat and human, in order to provide a perspective on the relative development and structural organization of the main subdivisions of the entorhinal cortex in two model organisms widely used to decipher the basic functional principles of the human medial temporal lobe memory system. Altogether, these data provide fundamental information on the number of functional units that comprise the entorhinal-hippocampal circuits and should be considered in order to build realistic models of the medial temporal lobe memory system.

Connectomics of the zebrafish's lateral-line neuromast reveals wiring and miswiring in a simple microcircuit.

The lateral-line neuromast of the zebrafish displays a restricted, consistent pattern of innervation that facilitates the comparison of microcircuits across individuals, developmental stages, and genotypes. We used serial blockface scanning electron microscopy to determine from multiple specimens the neuromast connectome, a comprehensive set of connections between hair cells and afferent and efferent nerve fibers. This analysis delineated a complex but consistent wiring pattern with three striking characteristics: each nerve terminal is highly specific in receiving innervation from hair cells of a single directional sensitivity; the innervation is redundant; and the terminals manifest a hierarchy of dominance. Mutation of the canonical planar-cell-polarity gene vangl2, which decouples the asymmetric phenotypes of sibling hair-cell pairs, results in randomly positioned, randomly oriented sibling cells that nonetheless retain specific wiring. Because larvae that overexpress Notch exhibit uniformly oriented, uniformly innervating hair-cell siblings, wiring specificity is mediated by the Notch signaling pathway.

An ascending visual pathway to the dorsal telencephalon through the optic tectum and nucleus prethalamicus in the yellowfin goby Acanthogobius flavimanus (Temminck & Schlegel, 1845).

Dual visual pathways reaching the telencephalon appear to be an ancient vertebrate trait, but some teleost fish seem to possess only one pathway via the optic tectum. We undertook the present study to determine if and when this loss occurred during evolution. Tracer injection experiments to the optic nerve, the optic tectum, and the dorsal telencephalon were performed in the present study, to investigate ascending visual pathways to the dorsal telencephalon in an acanthopterygian teleost, the yellowfin goby Acanthogobius flavimanus (Temminck & Schlegel, 1845). We confirmed the presence of a nucleus prethalamicus (PTh) in the goby, which has been convincingly identified only in holocentrids, suggesting that this nucleus is present in other acanthopterygians. We found that the optic tectum projects to the PTh bilaterally. The PTh projects in turn to the dorsal telencephalon, ipsilaterally. These results suggest that the yellowfin goby possesses only an extrageniculate-like pathway, while a geniculate-like pathway could not be identified. This situation is common with that of holocentrids and may be a character common in acanthopterygians. It is possible that a geniculate-like system was lost in the common ancestor of acanthopterygians, although the scenario for the evolution of ascending visual systems in actinopterygians remains uncertain due to the lack of precise knowledge in a number of actinopterygian taxons.