Crossed Connections From Insular Cortex to the Contralateral Thalamus

Sensory information in all modalities, except olfaction, is processed at the level of the thalamus before subsequent transmission to the cerebral cortex. This incoming sensory stream is refined and modulated in the thalamus by numerous descending corticothalamic projections originating in layer 6 that ultimately alter the sensitivity and selectivity for sensory features. In general, these sensory thalamo-cortico-thalamic loops are considered strictly unilateral, i.e., no contralateral crosstalk between cortex and thalamus. However, in contrast to this canonical view, we characterize here a prominent contralateral corticothalamic projection originating in the insular cortex, utilizing both retrograde tracing and cre-lox mediated viral anterograde tracing strategies with the Ntsr1-Cre transgenic mouse line. From our studies, we find that the insular contralateral corticothalamic projection originates from a separate population of layer 6 neurons than the ipsilateral corticothalamic projection. Furthermore, the contralateral projection targets a topographically distinct subregion of the thalamus than the ipsilateral projection. These findings suggest a unique bilateral mechanism for the top-down refinement of ascending sensory information.

Primary Graviceptive System and Astasia: Case Report and Literature Review

Purpose of ReviewAstasia refers to the inability to maintain upright posture during standing, despite having full motor strength. However, the pathophysiology and neural pathways of astasia remains unclear.Recent FindingsWe analyzed 26, including ours, non-psychogenic astasia patients in English literature. Seventy-three percent of them were man, 73% were associated with other neurologic symptoms and 62% of reported lesions were at right side. Contralateral lateropulsion was very common followed by retropulsion while describing astasia. Infarction (54%) was the most commonly reported cause. Thalamus (65%) was the most commonly reported location. Infarction being the mostly likely to recover (mean:10.6 days), while lesions at brainstem had longer time to recover (mean: 61.6 days).SummaryThe underlying interrupted pathway may be the primary graviceptive system, which composed of at least five unilateral and contralateral projection fibers from vestibular nuclei to thalamic nuclei, and thalamo-cortical projections including subcortical white matter tracts and cortical areas.

Transneuronal Retinal Projections to V1 Form “Minicolumns” in Layer 1: Comparison with Projections to Layer 4 in Normal and Visually Deprived Long Evans Rats

Lattice-like patterns in layer 1 (L1) of primary visual cortex (V1) of mice have been demonstrated following injections of tracers into the lateral geniculate nucleus (LGN) of the thalamus (Ji et al., 2015). To distinguish the ipsilateral and contralateral components of this projection, we made unilateral intravitreal injections of the transneuronal tracer WGA-HRP in Long Evans rats, a strain in which projections to L4 form ocular dominance columns (ODCs, Laing et al., 2015). We have shown that ODCs form by postnatal day 10 (P10), and that they are susceptible to monocular enucleation and monocular deprivation by eyelid suture during development (Olavarria et al., 2021). We now show that lattice-like patterns in L1 are also visible by P10, but unlike the normal contralateral projection to L4, which does not encroach into ipsilateral eye territory, the contralateral projections to layer 1 in P10 and adult normal rats are distributed throughout V1, including ipsilateral eye territories. Moreover, this pattern does not change in visually deprived rats, suggesting that L1 projections are not susceptible to visual deprivation as L4 projections are. Notably, contralateral projections to L4 in visually deprived rats do encroach into ipsilateral eye territory, resembling the projection pattern in L1. Together, these observations suggest that geniculate projections to L1 or L4 differ not only in the cues guiding their target selection, but also in cues determining their distribution within V1, and the way they respond to visual deprivation during development.

A specialized reciprocal connectivity suggests a link between the mechanisms by which the superior colliculus and parabigeminal nucleus produce defensive behaviors in rodents

The parabigeminal nucleus (PBG) is the mammalian homologue to the isthmic complex of other vertebrates. Optogenetic stimulation of the PBG induces freezing and escape in mice, a result thought to be caused by a PBG projection to the central nucleus of the amygdala. However, the isthmic complex, including the PBG, has been classically considered satellite nuclei of the Superior Colliculus (SC), which upon stimulation of its medial part also triggers fear and avoidance reactions. As the PBG-SC connectivity is not well characterized, we investigated whether the topology of the PBG projection to the SC could be related to the behavioral consequences of PBG stimulation. To that end, we performed immunohistochemistry, in situ hybridization and neural tracer injections in the SC and PBG in a diurnal rodent, the Octodon degus. We found that all PBG neurons expressed both glutamatergic and cholinergic markers and were distributed in clearly defined anterior (aPBG) and posterior (pPBG) subdivisions. The pPBG is connected reciprocally and topographically to the ipsilateral SC, whereas the aPBG receives afferent axons from the ipsilateral SC and projected exclusively to the contralateral SC. This contralateral projection forms a dense field of terminals that is restricted to the medial SC, in correspondence with the SC representation of the aerial binocular field which, we also found, in O. degus prompted escape reactions upon looming stimulation. Therefore, this specialized topography allows binocular interactions in the SC region controlling responses to aerial predators, suggesting a link between the mechanisms by which the SC and PBG produce defensive behaviors.

Refinement of the Primate Corticospinal Pathway During Prenatal Development

Perturbation of the developmental refinement of the corticospinal (CS) pathway leads to motor disorders. While non-primate developmental refinement is well documented, in primates invasive investigations of the developing CS pathway have been confined to neonatal and postnatal stages when refinement is relatively modest. Here, we investigated the developmental changes in the distribution of CS projection neurons in cynomolgus monkey (Macaca fascicularis). Injections of retrograde tracer at cervical levels of the spinal cord at embryonic day (E) 95 and E105 show that: (i) areal distribution of back-labeled neurons is more extensive than in the neonate and dense labeling is found in prefrontal, limbic, temporal, and occipital cortex; (ii) distributions of contralateral and ipsilateral projecting CS neurons are comparable in terms of location and numbers of labeled neurons, in contrast to the adult where the contralateral projection is an order of magnitude higher than the ipsilateral projection. Findings from one largely restricted injection suggest a hitherto unsuspected early innervation of the gray matter. In the fetus there was in addition dense labeling in the central nucleus of the amygdala, the hypothalamus, the subthalamic nucleus, and the adjacent region of the zona incerta, subcortical structures with only minor projections in the adult control.

Refinement of the primate corticospinal pathway during prenatal development

Perturbation of the developmental refinement of the corticospinal pathway leads to motor disorders. In non-primates developmental refinement is well documented, however in primates invasive investigations of the developing corticospinal pathway have been confined to neonatal and postnatal stages when refinement is relatively modest.Here, we investigated the developmental changes in the distribution of corticospinal projection neurons in cynomolgus monkey. Injections of retrograde tracer at the cervical levels of the spinal cord at embryonic day (E) 95 and E105 show that (i) areal distribution of back-labeled neurons is more extensive than in the neonate and dense labeling is found in prefrontal, limbic, temporal and occipital cortex; (ii) distributions of contra- and ipsilateral projecting corticospinal neurons are comparable in terms of location and numbers of labeled neurons, in contrast to the adult where the contralateral projection is an order of magnitude higher than the ipsilateral projection. Findings from one largely restricted injection suggest a hitherto unsuspected early innervation of the gray matter.In the fetus there was in addition dense labeling in the central nucleus of the amygdala, the hypothalamus, the subthalamic nucleus and the adjacent region of the zona incerta, subcortical structures with only minor projections in the adult control.

Developmental system drift in motor ganglion patterning between distantly related tunicates

The larval nervous system of the solitary tunicate Ciona is a simple model for the study of chordate neurodevelopment. The development and connectivity of the Ciona Motor Ganglion (MG) has been studied in fine detail, but how this important structure develops in other tunicates is not well known. By comparing gene expression patterns in the developing MG of the distantly related tunicate Molgula occidentalis, we found that its patterning is highly conserved compared to the Ciona MG. MG neuronal subtypes in Molgula were specified in the exact same positions as in Ciona, though the timing of subtype-specific gene expression onset was slightly shifted to begin earlier, relative to mitotic exit and differentiation. In transgenic Molgula embryos electroporated with Dmbx reporter plasmids, we were also able to characterize the morphology of the lone pair of descending decussating neurons (ddNs) in Molgula, revealing the same unique contralateral projection seen in Ciona ddNs and their putative vertebrate homologs the Mauthner cells. Although Dmbx expression labels the ddNs in both species, cross-species transgenic assays revealed significant changes to the cis-regulatory logic underlying Dmbx transcription. We found that Dmbx cis-regulatory DNAs from Ciona can drive highly specific reporter gene expression in Molgula ddNs, but Molgula sequences are not active in Ciona ddNs. This acute divergence in the molecular mechanisms that underlie otherwise functionally conserved cis-regulatory DNAs supports the recently proposed idea that the extreme genetic plasticity observed in tunicates may be attributed to the extreme rigidity of the spatial organization of their embryonic cell lineages.

The subtlety of simple eyes: the tuning of visual fields to perceptual challenges in birds

Birds show interspecific variation both in the size of the fields of individual eyes and in the ways that these fields are brought together to produce the total visual field. Variation is found in the dimensions of all main parameters: binocular region, cyclopean field and blind areas. There is a phylogenetic signal with respect to maximum width of the binocular field in that passerine species have significantly broader field widths than non-passerines; broadest fields are found among crows (Corvidae). Among non-passerines, visual fields show considerable variation within families and even within some genera. It is argued that (i) the main drivers of differences in visual fields are associated with perceptual challenges that arise through different modes of foraging, and (ii) the primary function of binocularity in birds lies in the control of bill position rather than in the control of locomotion. The informational function of binocular vision does not lie in binocularity per se (two eyes receiving slightly different information simultaneously about the same objects from which higher-order depth information is extracted), but in the contralateral projection of the visual field of each eye. Contralateral projection ensures that each eye receives information from a symmetrically expanding optic flow-field from which direction of travel and time to contact targets can be extracted, particularly with respect to the control of bill position.

Current source density analysis of contra- and ipsilateral isthmotectal connections of the frog

The nucleus isthmi (NI) of the frog receives input from the ipsilateral optic tectum and projects back to both optic tecta. After ablation of NI, frogs display no visually elicited prey-catching or threat avoidance behavior. Neural mechanisms that underlie the loss of such important behavior have not been solved. Electrophysiological examination of the contralateral isthmotectal projection has proved that it contributes to binocular vision. On the other hand, there are very few physiological investigations of the ipsilateral isthmotectal projection. In this study, current source density (CSD) analysis was applied to contra- and ipsilateral isthmotectal projections. The contralateral projection produced monosynaptic sinks in superficial layers and in layer 8. The results confirmed former findings obtained by single unit recordings. The ipsilateral projection elicited a prominent monosynaptic sink in layer 8. Recipient neurons were located in layers 6–7. These results, combined with those from the former intracellular study, led to the following neuronal circuit. Afferents from the ipsilateral NI inhibit non-efferent pear shaped neurons in the superficial layers, and strongly excite large ganglionic neurons projecting to the descending motor regions. Thus feedback to the output neurons strengthens the visually elicited responses.