Transcranial temporal interference stimulation (tTIS) is a novel non-invasive neuromodulation technique with the potential to precisely target deep brain structures. This study explores the neural and behavioral effects of tTIS on the superior colliculus (SC), a region involved in eye movement control, in mice. Computational modeling revealed that tTIS delivers more focused stimulation to the SC than traditional transcranial alternating current stimulation. In vivo experiments, including Ca²⁺ signal recordings and eye movement tracking, showed that tTIS effectively modulates SC neural activity and induces eye movements. A significant correlation was found between stimulation frequency and saccade frequency, suggesting direct tTIS-induced modulation of SC activity. These results demonstrate the precision of tTIS in targeting deep brain regions and regulating eye movements, highlighting its potential for neuroscientific research and therapeutic applications.
Animals ; Superior Colliculi/physiology* ; Transcranial Direct Current Stimulation/methods* ; Eye Movements/physiology* ; Male ; Mice ; Mice, Inbred C57BL

The looming stimulus-evoked flight response to approaching predators is a defensive behavior in most animals. However, how looming stimuli are detected in the retina and transmitted to the brain remains unclear. Here, we report that a group of GABAergic retinal ganglion cells (RGCs) projecting to the superior colliculus (SC) transmit looming signals from the retina to the brain, mediating the looming-evoked flight behavior by releasing GABA. GAD2-Cre and vGAT-Cre transgenic mice were used in combination with Cre-activated anterograde or retrograde tracer viruses to map the inputs to specific GABAergic RGC circuits. Optogenetic technology was used to assess the function of SC-projecting GABAergic RGCs (scpgRGCs) in the SC. FDIO-DTA (Flp-dependent Double-Floxed Inverted Open reading frame-Diphtheria toxin) combined with the FLP (Florfenicol, Lincomycin & Prednisolone) approach was used to ablate or silence scpgRGCs. In the mouse retina, GABAergic RGCs project to different brain areas, including the SC. ScpgRGCs are monosynaptically connected to parvalbumin-positive SC neurons known to be required for the looming-evoked flight response. Optogenetic activation of scpgRGCs triggers GABA-mediated inhibition in SC neurons. Ablation or silencing of scpgRGCs compromises looming-evoked flight responses without affecting image-forming functions. Our study reveals that scpgRGCs control the looming-evoked flight response by regulating SC neurons via GABA, providing novel insight into the regulation of innate defensive behaviors.
Animals ; Superior Colliculi/physiology* ; Retinal Ganglion Cells/physiology* ; GABAergic Neurons/physiology* ; Mice, Transgenic ; Mice ; Optogenetics ; Visual Pathways/physiology* ; Mice, Inbred C57BL ; Photic Stimulation/methods* ; gamma-Aminobutyric Acid/metabolism* ; Male

The superior colliculus (SC), one of the most well-characterized midbrain sensorimotor structures where visual, auditory, and somatosensory information are integrated to initiate motor commands, is highly conserved across vertebrate evolution. Moreover, cell-type-specific SC neurons integrate afferent signals within local networks to generate defined output related to innate and cognitive behaviors. This review focuses on the recent progress in understanding of phenotypic diversity amongst SC neurons and their intrinsic circuits and long-projection targets. We further describe relevant neural circuits and specific cell types in relation to behavioral outputs and cognitive functions. The systematic delineation of SC organization, cell types, and neural connections is further put into context across species as these depend upon laminar architecture. Moreover, we focus on SC neural circuitry involving saccadic eye movement, and cognitive and innate behaviors. Overall, the review provides insight into SC functioning and represents a basis for further understanding of the pathology associated with SC dysfunction.
Superior Colliculi/physiology* ; Saccades ; Neurons/physiology*

Environmental threats often trigger innate defensive responses in mammals. However, the gradual development of functional properties of these responses during the postnatal development stage remains unclear. Here, we report that looming stimulation in mice evoked flight behavior commencing at P14-16 and had fully developed by P20-24. The visual-evoked innate defensive response was not significantly altered by sensory deprivation at an early postnatal stage. Furthermore, the percentages of wide-field and horizontal cells in the superior colliculus were notably elevated at P20-24. Our findings define a developmental time window for the formation of the visual innate defense response during the early postnatal period and provide important insight into the underlying mechanism.
Animals ; Evoked Potentials, Visual ; Fear/physiology* ; Mammals ; Mice ; Mice, Inbred C57BL ; Neurons/physiology* ; Superior Colliculi/physiology*

In order to present the optimal neuroscience tutorial material for medical students and researchers, this study is aimed to make neuro-digital slide and neuro-atlas based on the histological specimens of human spinal cord and brain stem. Cadavers which had agreed for organ donation for research purpose were used in this study. Brains and spinal cords were extracted within 24 hours after death, and then fixed with 10% neutral buffered formalin. Paraffin blocks were made with the following regions; 8 regions from the spinal cord (the levels of the upper cervical segment, the cervical enlargement, the upper thoracic segment, the mid thoracic segment, the lower thoracic segment, the upper lumbar segment, the lumbar enlargement, the sacral segment), 14 regions from the brain stem (the levels of the spinomedullary junction, the pyramidal decussation, the medial lemniscus decussation, the obex, the mid-olivary medulla, the upper medulla, the pontomedullary junction, the lower pons, the mid pons, the upper pons, the isthmus rhombencephali, the inferior colliculus, the superior colliculus, the posterior commissure). Using virtual microscope software, we made digital neuro-slides which can be used anywhere and anytime regardless of equipment of microscope. To help understanding anatomy and functions of nervous tissue, we also made neuro-atlas based on the digital slide images. As results, the outline and detailed structures of nuclei and tracts are easily discriminated and also matched with marks and nomenclatures of neuro-atlas. Moreover, the cytoarchitecture of each nucleus and histological features can be well distinguished. We hope that this product would be used as a useful neuroscience tutorial material for the medical and paramedical school students, clinical trainees like interns and residents, and also neuroscience researchers.
Brain ; Brain Stem ; Formaldehyde ; Humans ; Inferior Colliculi ; Neurosciences ; Paraffin ; Pons ; Pyramidal Tracts ; Spinal Cord ; Students, Medical ; Superior Colliculi ; Tissue and Organ Procurement

EphA/ephrin-A mediated signaling has emerged as a key mechanism regulating axon guidance and topographic mapping, particularly in the well-characterized visual system from the retina to the superior colliculus (SC). In this study, EphA8 bacterial artificial chromosome (BAC) was manipulated to contain a floxed eGFP and human ephrin-A5 expression cassette using homologous recombination method. In the mice containing the recombinant BAC, it was shown that GFP is expressed in an anterior>posterior gradient in the SC. Furthermore, when these mice were crossed with the transgenic mice expressing Cre under the EphA8 promoter, it was evident that a GFP expression cassette was eliminated, and that human ephrin-A5 was ectopically expressed in the anterior region of the SC. This transgenic model would be useful to analyze the role of ephrin-A5 in the SC during the retinocollicular topography formation.
Animals ; Axons ; Chromosomes, Artificial, Bacterial ; Ephrin-A5 ; Homologous Recombination ; Humans ; Mice ; Mice, Transgenic ; Retina ; Superior Colliculi

OBJECTIVEA few investigations have been reported about pretectal suppressive influences on the optic tectum of frog, but characteristics of tectal activity to pretectal input are left unknown. We made intracellular recordings to demonstrate the unexpected complexity in synaptic mechanisms involved in the suppressive influences of pretecal stimulation on the tectal cells.

METHODSIn the present study, we investigated the neuronal activity evoked by pretectal (Lpd/P) nuclei stimulation using intracellular recording technique.

RESULTSThe pretectal stimulation mainly elicited two types of responses in the ipsilateral tectum: an excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP) and a pure IPSP. The latter predominated in the tectal cells responding to pretectal stimulation. In a few cells, biphasic hyperpolarization appeared under stronger stimulus intensities. The spikes of tecto-pretectal projecting cells elicited by antidromical stimulation were recorded in the ipsilateral tectum, which revealed reciprocal connections between the tectum and particular pretectal nuclei. The synaptic natures underlying pretecto-tectal information transformation have also been demonstrated. EPSPs with short latencies were concluded to be monosynaptic. Most IPSPs were generated through polysynaptic paths, but monosynaptic IPSPs were also recorded in the tectum. Nearly 98% of impaled tectal cells (except for antidromically projecting cells) showed inhibitory responses to pretectal stimulation.

CONCLUSIONThe results provide strong evidence that pretectal cells broadly inhibit tectal neurons as that has suggested by behavioral and extracellular recording studies.

Animals ; Electric Stimulation ; Excitatory Postsynaptic Potentials ; physiology ; Female ; Inhibitory Postsynaptic Potentials ; physiology ; Male ; Neural Inhibition ; physiology ; Neural Pathways ; cytology ; physiology ; Neurons ; physiology ; Rana catesbeiana ; physiology ; Superior Colliculi ; cytology ; physiology

Purpose: To evaluate the tracing of optic nerve tract using manganese enhanced magnetic resonance imaging. Materials and Methods: After injecting 30 microliter of MnCl2 (1 mol) into the retina of female New Zealand white rabbit, the contrast enhancements at major anatomical structures of optic nerve tract were evaluated by high resolution T1-weighted images 12 hours, 24 hours, and 48 hours after MnCl2 injection using 3D FSPGR (Fast Spoiled Gradient Recalled echo) pulse sequence at 1.5 T clinical MR scanner with high performance gradient system. Also, for quantitative evaluation, the signal-to-noise ratios of circular ROI on anatomical locations were measured. Results: The major structures on the optic nerve tract were enhanced after injecting MnCl2. The structures, which showed enhancement, were right optic nerve, optic chiasm, left optic tract, left lateral geniculate nucleus, left superior colliculus. The structures on the contralateral optic pathway to the right retina were enhanced whereas the structures on the ipsilateral pathway did not show enhancement. Conclusion: The Mn transport through axonal pathway of optic nerve system was non-invasively observed after injecting MnCl2 at the retina, which is the end terminal of optic nerve system. This Mn transport seems to occur by voltage gated calcium (Ca2+) channel and in case of direct injection into the retina, the fast transport pathway of voltage gated calcium channel seems to be responsible for Mn transport.
Axons ; Calcium ; Calcium Channels ; Evaluation Studies as Topic ; Female ; Humans ; Magnetic Resonance Imaging ; Manganese ; New Zealand ; Optic Chiasm ; Optic Nerve ; Retina ; Signal-To-Noise Ratio ; Superior Colliculi ; Visual Pathways*

Calcium-binding proteins play an important role in the protection, differentiation, and reorganization of the central nervous system. The effects of neonatal retinal deafferentiation on calretinin, and tracing of retinotectal pathway were examined immunohistochemically in the superficial layer of the rat superior colliculus. Tracing with cholera toxin was revealed on the superior colliculus contralateral to the ocular injection. On the contralateral side of superior colliculus, the calretinin-immunoreactive (IR) cells were dramatically increased, calretinin-IR fibers were markedly decreased in the superficial layer. These results show that retinal deafferentation results in an increase of calretinin-immunoreactive cells within the superficial layers of the superior colliculus, which suggest reorganization of neurons in superior colliculus.
Animals ; Calbindin 2 ; Calcium-Binding Proteins ; Central Nervous System ; Cholera Toxin ; Eye Enucleation* ; Neurons ; Rats* ; Retinaldehyde ; Superior Colliculi

PURPOSE: To investigate the change of the Beta adrenergic system in the rat visual cortex and superior colliculus after visual deprivation during a critical period of postnatal development. METHODS: The changes of beta 1 and beta 2 adrenergic receptor mRNA were investigated by using northern blot analysis in the rat visual cortex and superior colliculus. The right eyelid of visually deprived rat was sutured at the 10th postnatal days. After visual deprivation for 4 weeks, the rat were sacrificed and the visual cortex and superior colliculus tissues were removed for analysis. RESULTS: Beta 1 and beta 2 adrenergic receptor mRNA expression was decreased in the contralateral visual cortex to the deprived eye. In the superior colliculus, beta 2 adrenergic receptor mRNA expression increased in both sides, but a much greater increase was shown in the ipsilateral superior colliculus than the contralateral side. CONCLUSIONS: These results suggests that visual deprivation during a critical period of postnatal development influences the beta adrenergic system in the rat visual cortex and superior colliculus.
Animals ; Blotting, Northern ; Critical Period (Psychology) ; Eyelids ; Rats* ; Receptors, Adrenergic ; RNA, Messenger* ; Superior Colliculi* ; Visual Cortex*