The Superior Colliculus: Cell Types, Connectivity, and Behavior

Abstract

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.

Keywords: GABAergic neurons; Glutamatergic neurons; Innate behaviors; Neuronal circuits; Superior colliculus.

Fig. 1

Superior colliculus/optic tectum afferent and efferent connections across vertebrates. A Humans. B Rhesus monkeys. C Mice. D Zebrafish. Using schematic sagittal brain sections, the figure shows homologous circuits across species for the superior colliculus (SC) and optic tectum (OT), with inputs to the SC in green and SC outputs in blue. Light blue represents SC connectivity, which is not yet fully determined. Light red indicates that the nucleus is reciprocally connected with the SC/OT. The middle and right-hand columns show schematics and coronal histological sections, respectively, of the SC or OT in different species. AIC, agranular insular cortex; A/LIP, anterior/lateral intraparietal area; Amyg, amygdala; AUD, auditory cortex; ATN, anterior group of the dorsal thalamus; CIN, cingulate cortex; CnB, cerebellar nucleus; cMRF, central mesencephalic reticular formation; CUN, cuneiform nucleus; DLPFC, dorsolateral prefrontal cortex; FEF, frontal eye field; GP, globus pallidus; GRN, gigantocellular reticular nucleus; HB, hind brain; IC, inferior colliculus; ILM, intralaminar nuclei of the thalamus; IO, inferior olivary complex; LHA, lateroanterior hypothalamic nucleus; LC, locus coeruleus; LDT, laterodorsal tegmentum; LGN, lateral geniculate nucleus; LHb, lateral habenular; LP, lateral posterior thalamic nucleus; M1, primary motor cortex; M2, secondary motor cortex; MC, motor cortex; MD, mediodorsal thalamus; MDRN, medullary reticular nucleus; MRN, midbrain reticular nucleus; MT, middle temporal area; NI, nucleus isthmi; NRTP, nucleus reticularis tegmenti pontis; ORB, orbital area; PAG, periaqueductal grey; PB, parabrachial nucleus; PBGN, parabigeminal nucleus; PCG, postcentral gyrus; PFG, inferior parietal lobule area 7b; PUL, pulvinar; PM, premotor cortex; PN, pretectal nucleus including anterior, medial, and posterior; PT, pretectum; PTL, parietal association cortex; PPN, pedunculotegmental nucleus; PRN, pontine reticular nucleus; PSV, principal sensory nucleus of the trigeminal; PVN, paraventricular nucleus of the hypothalamus; Re, reuniens thalamic nucleus; RF, reticular formation; RGC, retinal ganglion cell; RH, rostral hypothalamus; RN, raphe nucleus; RPO, nucleus raphe pontis; S1, primary somatosensory cortex; S2, secondary somatosensory cortex; SAG, nucleus sagulum; SEF, supplementary eye field; SI, substantia innominata; SNr, substantia nigra pars reticulata; SOC, superior olivary complex; SPF, subparafascicular nucleus; SPV, spinal nucleus of the trigeminal; TEa, temporal association area; TEG, tegmentum; Tha, thalamus; TPJ, temporoparietal junction; TRN, tegmental reticular nucleus; V1, primary visual cortex; V2, secondary visual cortex; VC, visual cortex; VENT, ventral group of the dorsal thalamus; VI, abducens nucleus; VII, facial motor nucleus; VLPFC, ventral lateral prefrontal cortex; VTA, ventral tegmental area; ZI, zona incerta. Right panel of A is adapted from Michigan State University, https://brains.anatomy.msu.edu/brains/human/coronal/2390_cell_labelled.html. Right panels of B and C are from the Allen Institute for Brain Science http://www.blueprintnhpatlas.org/static/referencedata, http://mouse.brain-map.org/static/atlas, Right panel of D from The Zebrafish Information Network http://zfin.org/ZDB-IMAGE-011218-26.

Fig. 2

Inputs to and outputs from superior colliculus/optic tectum neurons. Schematic of the synaptic connections identified to date. Superior colliculus (SC) GABAergic neurons receive inputs from retinal ganglion cells (RGC), the primary visual cortex (V1), cingulate cortex (CIN), auditory cortex (AUD), GABAergic inputs from the midbrain substantia nigra pars reticulata (SNr), and cholinergic inputs from the brainstem parabrachial region (PB). Glutamatergic SC neurons receive inputs from GABAergic neurons from the SNr, glutamate inputs from the AUD, and projections with undetermined neurotransmitters from the CIN, V1, primary motor cortex (M1), primary somatosensory cortex (S1), secondary somatosensory cortex (S2), parietal association cortex (PTL), agranular insular cortex (AIC), orbital area (ORB), lateral posterior thalamus (LP), ventral group of the dorsal thalamus (VENT) including ventral medial and posteromedial nuclei of the thalamus, and the subparafascicular nucleus (SPF). SC neurons also receive inputs from the cerebral cortex that mainly involve the ventrolateral prefrontal area (VLPFC), inferior parietal lobule area 7b (PFG), anterior and lateral intraparietal area (AIP and LIP), temporal association area (TEa), retrosplenial area cortex (RSP), prelimbic area cortex (PL), infralimbic area cortex (ILA), secondary motor cortex (M2) including dorsal and ventral premotor cortex, frontal eye field (FEF), and the supplementary eye field (SEF). Moreover, SC neurons receive thalamic input from the lateral habenula (LHb), lateral geniculate complex (LGN), midbrain inputs from the inferior colliculus (IC), midbrain reticular nucleus (MRN), and nucleus sagulum (SAG), and hindbrain input from the principal sensory nucleus of the trigeminal (PSV), spinal nucleus of the trigeminal (SPV), and the cerebellar nuclei (CnB). Also, SC neurons receive inputs from GABAergic and dopaminergic projections from the zona incerta (ZI), oxytocin-positive neurons in the paraventricular nucleus of the hypothalamus (PVN), midbrain GABAergic inputs from the pretectal nuclear complex (PNC), cholinergic inputs from the nucleus isthmi (NI), dopaminergic inputs from the substantia nigra pars compacta (SNc), serotonergic inputs from the periaqueductal grey (PAG) and raphe nucleus (RN), and a hindbrain tyrosine hydroxylase projection from the locus coeruleus (LC). SC glutamate neurons target the LP and PAG, GABA neurons of the ventral tegmental area (VTA), ZI and central mesencephalic reticular formation (cMRF). SC GABA neurons target VTA dopamine neurons. SC parvalbumin-positive neurons target the parabigeminal nucleus (PBGN), pretectum (PT) and the LP. SC neurons also target the globus pallidus (GP) and substantia innominata (SI), thalamic nuclei including the thalamic reticular nucleus (RT), LGN, pulvinar (PUL) and VENT, anterior group (ANT), lateral group (LAT) of the dorsal thalamus and reuniens thalamic nucleus (Re), as well as the SPF, intralaminar nuclei of the thalamus (ILM), LHb, mediodorsal thalamus (MD), the hypothalamus area including the subthalamic nucleus (STN), PVN, lateral hypothalamic area (LHA) and midbrain nucleus SNc, SAG, MRN, red nucleus (RN), pedunculopontine nucleus (PPN), CUN, inferior colliculus (IC) and hindbrain area tegmental reticular nucleus (TRN), gigantocellular reticular nucleus (GRN), medullary reticular nucleus (MDRN), pontine reticular nucleus (PRN), facial nucleus (FN), abducens nucleus (VI), nucleus raphe pontis (RPO), PSV, SPV, superior olivary complex (SOC), PB, laterodorsal tegmental nucleus (LDT) and its homologous structure the tegmentum (TEG), and inferior olivary complex (IO), and the pre-Bötzinger complex (preBötC). Lines and arrows extending into the box for the SCs, SCi, and SCd indicate that these pathways have confirmed subregion targeting within the SC. Lines and arrows outside the box indicate that targeting of these pathways within the SC has not been shown to have subregion specificity.

Fig. 3

Contributions of specific superior colliculus circuits to eye movements and innate behaviors. A Schematic of the inputs onto GABAergic and glutamatergic SC neurons proposed to contribute to eye movements and salient vision. B Schematic of the sources of glutamatergic inputs synapsing on zona incerta (ZI) GABAergic neurons shown to participate in prey-capture behavior [hunting test with the introduction of a cockroach (prey) to a mouse (predator) in a confined arena]. C Schematic of the inputs to GABAergic SC neurons proposed to contribute to wakefulness (an acute pulse that increases wakefulness in nocturnal animals). D Schematic of inhibitory inputs from the SNr to SC neurons proposed to contribute to drinking behavior. E Schematic of the glutamatergic, parvalbumin-positive, or tyrosine hydroxylase-positive inputs to the SC that have been proposed to contribute to visual fear behavior [an animal is exposed to an expanding dark disc (looming) stimulus to the upper visual field to mimic an approaching aerial predator]. VTA, ventral tegmental area; CEA, central medial amygdala; LP, lateral posterior thalamus; LA, lateral amygdala; LC, locus coeruleus; PBGN, parabigeminal nucleus; PAG, periaqueductal grey; SNc, substantia nigra pars compacta; RGC, retinal ganglion cells; SNr, substantia nigra pars reticulata; V1, primary visual cortex; PT, pretectum; cMRF, central mesencephalic reticular formation; PPRF, paramedian pontine reticular formation; PNC, pretectal nuclear complex; SCi, intermediate gray layer of the SC; SCs, superficial layer of the SC; FEF, frontal eye field; PB, parabrachial region.