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.

BMP Signaling Interferes with Optic Chiasm Formation and Retinal Ganglion Cell Pathfinding in Zebrafish

Decussation of axonal tracts is an important hallmark of vertebrate neuroanatomy resulting in one brain hemisphere controlling the contralateral side of the body and also computing the sensory information originating from that respective side. Here, we show that BMP interferes with optic chiasm formation and RGC pathfinding in zebrafish. Experimental induction of BMP4 at 15 hpf results in a complete ipsilateral projection of RGC axons and failure of commissural connections of the forebrain, in part as the result of an interaction with shh signaling, transcriptional regulation of midline guidance cues and an affected optic stalk morphogenesis. Experimental induction of BMP4 at 24 hpf, resulting in only a mild repression of forebrain shh ligand expression but in a broad expression of pax2a in the diencephalon, does not per se prevent RGC axons from crossing the midline. It nevertheless shows severe pathologies of RGC projections e.g., the fasciculation of RGC axons with the ipsilateral optic tract resulting in the innervation of one tectum by two eyes or the projection of RGC axons in the direction of the contralateral eye.

BMP signaling interferes with optic chiasm formation and retinal ganglion cell pathfinding in zebrafish

Decussation of axonal tracts is an important hallmark of vertebrate neuroanatomy resulting in one brain hemisphere controlling the contralateral side of the body and also computing the sensory information originating from that respective side. Here, we show that BMP interferes with optic chiasm formation and RGC pathfinding in zebrafish. Experimental induction of BMP4 at 15 hpf results in a complete ipsilateral projection of RGC axons and failure of commissural connections of the forebrain in part being the result of an interaction with shh signaling, transcriptional regulation of midline guidance cues and an affected optic stalk morphogenesis. Experimental induction of BMP4 at 24 hpf, resulting in only a mild repression of forebrain shh ligand expression but in a broad expression of pax2a in the diencephalon, does not per se prevent RGC axons from crossing the midline. It nevertheless shows severe pathologies of RGC projections e.g. the fasciculation of RGC axons with the ipsilateral optic tract resulting in the innervation of one tectum by two eyes or the projection of RGC axons in the direction of the contralateral eye.

Retinal Ganglion Cell Axon Wiring Establishing the Binocular Circuit

Binocular vision depends on retinal ganglion cell (RGC) axon projection either to the same side or to the opposite side of the brain. In this article, we review the molecular mechanisms for decussation of RGC axons, with a focus on axon guidance signaling at the optic chiasm and ipsi- and contralateral axon organization in the optic tract prior to and during targeting. The spatial and temporal features of RGC neurogenesis that give rise to ipsilateral and contralateral identity are described. The albino visual system is highlighted as an apt comparative model for understanding RGC decussation, as albinos have a reduced ipsilateral projection and altered RGC neurogenesis associated with perturbed melanogenesis in the retinal pigment epithelium. Understanding the steps for RGC specification into ipsi- and contralateral subtypes will facilitate differentiation of stem cells into RGCs with proper navigational abilities for effective axon regeneration and correct targeting of higher-order visual centers.

Brainstem Neurons that Command Left/Right Locomotor Asymmetries

Descending command neurons instruct spinal networks to execute basic locomotor functions, such as which gait and what speed. The command functions for gait and speed are symmetric, implying that a separate unknown system directs asymmetric movements—the ability to move left or right. Here we report the discovery that Chx10-lineage reticulospinal neurons act to control the direction of locomotor movements in mammals. Chx10 neurons exhibit ipsilateral projection, and can decrease spinal limb-based locomotor activity ipsilaterally. This circuit mechanism acts as the basis for left or right locomotor movements in freely moving animals: selective unilateral activation of Chx10 neurons causes ipsilateral movements whereas inhibition causes contralateral movements. Spontaneous forward locomotion is thus transformed into an ipsilateral movement by braking locomotion on the ipsilateral side. We identify sensorimotor brain regions that project onto Chx10 reticulospinal neurons, and demonstrate that their unilateral activation can impart left/right directional commands. Together these data identify the descending motor system which commands left/right locomotor asymmetries in mammals.

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.

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.