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

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*

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*

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