The Superior Colliculus:Cell Types,Connectivity,and Behavior

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.

Time-dependent changes in eye-specific segregation in the dorsal lateral geniculate nucleus and superior colliculus of postnatal mice

Eye-specific segregation in the dorsal lateral geniculate nucleus(dLGN) and superior colliculus(SC) starts from the embryonic stage and continues to develop postnatally until eye-opening in mice. However, there have been few systematic studies on the details of this developmental process. Here, we carried out time-dependent studies of eye-specific segregation in the dLGN and SC. Our results demonstrated that the development of eye-specific segregation in the SC is completed before postnatal day 12(P12), which is earlier than in the dLGN(P20). During the whole period, ipsilateral and overlapping axonal projections decreased continuously in both the dLGN and SC. On the other hand, contralateral axonal projections showed little change, except for a slight decrease between P8 and P20 in the dLGN.

Short-Term Visual Experience Leads to Potentiation of Spontaneous Activity in Mouse Superior Colliculus

Spontaneous activity in the brain maintains an internal structured pattern that reflects the external environment,which is essential for processing information and developing perception and cognition.An essential prerequisite of spontaneous activity for perception is the ability to reverberate external information,such as by potentiation.Yet its role in the processing of potentiation in mouse superior colliculus(SC)neurons is less studied.Here,we used electrophysiological recording,optogenetics,and drug infusion methods to investigate the mechanism of potentiation in SC neurons.We found that visual experience potentiated SC neurons several minutes later in different developmental stages,and the similarity between spontaneous and visually-evoked activity increased with age.Before eye-opening,activation of retinal ganglion cells that expressed ChR2 also induced the potentiation of spontaneous activity in the mouse SC.Potentiation was dependenton stimulus number and showed feature selectivity for direction and orientation.Optogenetic activation of parvalbumin neurons in the SC attenuated the potentiation induced by visual experience.Furthermore,potentiation in SC neurons was blocked by inhibiting the glutamate transporter GLT1.These results indicated that the potentiation induced by a visual stimulus might play a key role in shaping the internal representation of the environment,and serves as a carrier for short-term memory consolidation.

Differentiation and functional connectivity of fetal tectal transplants

Data from studies analyzing the differentiation and functional connectivity of embryo nic neural tissue grafted into the mammalian nervous system has led to the clinical testing of the fetal graft approach in patients with neurodegenerative disease.While some success has been achieved,ethical concerns have led to a search for alternative therapeutic strategies,mostly exploring the use of neural precursors or neurons derived from pluripotent stem cells to replace damaged host neurons and restore lost circuitries.These more recent studies address questions of graft viability,differentiation,and connectivity similar to those posed by researchers in earlier fetal transplant work,thus reviews of the fetal graft literature may inform and help guide ongoing research in the stem cell/organoid field.This brief review describes some key observations from research into the transplantation of neural tissue into the rat visual syste m,focusing on grafts of the fetal supe rior colliculus(tectal grafts) into neonatal or adult hosts.In neonate hosts,grafts quickly develop connections with the underlying host mid b rain and attain a morphology typical of mature grafts by about 2 weeks.G rafts consistently contain numerous localized regions which,based on neurofibrillar staining,neuronal morphology(Golgi),neurochemistry,receptor expression,and glial architecture,are homologous to the stratum griseum supe rficiale of normal superior colliculus.These localized "patches" are also seen after explant culture and when donor tectal tissue is dissociated and reaggregated prior to transplantation.In almost all circumstances,host retinal innervation is restricted to these localized patches,but only those that are located adjacent to the graft surfa ce.Synapses are formed and there is evidence of functional drive.The only exception occurs when Schwann cells are added to dissociated tecta prior to reaggregation.In these co-grafts,the peripheral glia appear to compete with local target fa ctors and host retinal ingrowth is more widespread.Other afferent systems(e.g.,host co rtex,serotonin) show different patterns of innervation.The host cortical input originates more from extrastriate regions and establishes functional excitato ry synapses with grafted neurons.Finally,when grafted into optic tra ct lesions in adult rat hosts,spontaneously regrowing host retinal axons retain the capacity to selectively innervate the localized patches in embryonic tectal grafts,showing that the specific affinities between adult retinal axons and their targets are not lost during regeneration.While the research described here provides some pertinent information about development and plasticity in visual pathways,a more general aim is to highlight how the review of the extensive fetal graft lite rature may aid in an appreciation of the positive(and negative) fa ctors that influence survival,differentiation,connectivity and functionality of engineered cells and organoids transplanted into the central nervous system.

A new anterograde trans-synaptic tracer based on Sindbis virus

Mapping neural circuits is critical for understanding the structure and function of the nervous system.Engineered viruses are a valuable tool for tracing neural circuits.However,current tracers do not fully meet the needs for this approach because of various drawbacks,such as toxicity and characteristics that are difficult to modify.Therefore,there is an urgent need to develop a new tracer with low toxicity and that allows for long-term studies.In this study,we constructed an engineered Sindbis virus(SINV)expressing enhanced green fluorescent protein(EGFP)reporter gene(SINV-EGFP)and found that it had no significant difference in biological characterization compared with the wild-type Sindbis virus in BHK-21 cells and neurons in vitro.We injected the virus into the visual circuit of mouse brain and found that the virus infected neurons in the local injected site and anterogradely spread in the neural circuits.Although the efficiency of transmission was limited,the findings demonstrate that SINV can be used as a new anterograde tracer to map neural circuits in mouse brain and that it spreads exclusively in the anterograde direction.Further,use of SINV in mouse brain research will provide longer time windows for circuit tracing than is possible with herpes simplex virus and vesicular stomatitis virus tracers.

A Non-canonical Excitatory PV RGC–PV SC Visual Pathway for Mediating the Looming-evoked Innate Defensive Response

Parvalbumin-positive retinal ganglion cells(PV+RGCs)are an essential subset of RGCs found in various species.However,their role in transmitting visual information remains unclear.Here,we characterized PV+RGCs in the retina and explored the functions of the PV+RGC-mediated visual pathway.By applying multiple viral tracing strategies,we investigated the downstream of PV+RGCs across the whole brain.Interestingly,we found that the PV+RGCs provided direct monosynaptic input to PV+excitatory neurons in the superficial layers of the superior colliculus(SC).Ablation or suppression of SC-projecting PV+RGCs abolished or severely impaired the flight response to looming visual stimuli in mice without affecting visual acuity.Furthermore,using transcriptome expression profiling of individual cells and immunofluorescence colocalization for RGCs,we found that PV+RGCs are predominant glutamatergic neurons.Thus,our findings indicate the critical role of PV+RGCs in an innate defensive response and suggest a non-canonical subcortical visual pathway from excitatory PV+RGCs to PV+SC neurons that regulates looming visual stimuli.These results provide a potential target for intervening and treating diseases related to this circuit,such as schizophrenia and autism.

The Amygdala Responds Rapidly to Flashes Linked to Direct Retinal Innervation:A Flash-evoked Potential Study Across Cortical and Subcortical Visual Pathways

Rapid detection and response to visual threats are critical for survival in animals.The amygdala(AMY)is hypothesized to be involved in this process,but how it interacts with the visual system to do this remains unclear.By recording flash-evoked potentials simultaneously from the superior colliculus(SC),lateral posterior nucleus of the thalamus,AMY,lateral geniculate nucleus(LGN)and visual cortex,which belong to the cortical and subcortical pathways for visual fear processing,we investigated the temporal relationship between these regions in visual processing in rats.A quick flash-evoked potential(FEP)component was identified in the AMY.This emerged as early as in the LGN and was approximately 25 ms prior to the earliest component recorded in the SC,which was assumed to be an important area in visual fear.This quick P1 component in the AMY was not affected by restraint stress or corticosterone injection,but was diminished by RU38486,a glucocorticoid receptor blocker.By injecting a monosynaptic retrograde AAV tracer into the AMY,we found that it received a direct projection from the retina.These results confirm the existence of a direct connection from the retina to the AMY,that the latency in the AMY to flashes is equivalent to that in the sensory thalamus,and that the response is modulated by glucocorticoids.