RESUMEN
The mammalian superior colliculus (SC) is a sensorimotor midbrain structure responsible for orienting behaviors. Although many SC features are known, details of its intrinsic microcircuits are lacking. We used transgenic mice expressing reporter genes in parvalbumin-positive (PV+) and gamma aminobutyric acid-positive (GABA+) neurons to test the hypothesis that PV+ neurons co-localize GABA and form inhibitory circuits within the SC. We found more PV+ neurons in the superficial compared to the intermediate SC, although a larger percentage of PV+ neurons co-expressed GABA in the latter. Unlike PV+ neurons, PV+/GABA+ neurons showed predominantly rapidly inactivating spiking patterns. Optogenetic activation of PV+ neurons revealed direct and feedforward GABAergic inhibitory synaptic responses, as well as excitatory glutamatergic synapses. We propose that PV+ neurons in the SC may be specialized for a variety of circuit functions within the SC rather than forming a homogeneous, GABAergic neuronal subtype as they appear to in other regions of the brain.
Asunto(s)
Parvalbúminas/metabolismo , Colículos Superiores/fisiología , Sinapsis/fisiología , Ácido gamma-Aminobutírico/metabolismo , Animales , Neuronas GABAérgicas/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , Optogenética/métodosRESUMEN
Attenuation of visual activity in the superficial layers (SLs), stratum griseum superficiale and stratum opticum, of the superior colliculus during saccades may contribute to reducing perceptual blur during saccades and also may help prevent subsequent unwanted saccades. GABAergic neurons in the intermediate, premotor, layer (SGI), stratum griseum intermedium, send an inhibitory input to SL. This pathway provided the basis for a model proposing that the SGI premotor cells that project to brainstem gaze centers and discharge before saccades also activate neighboring GABAergic neurons that suppress saccade-induced visual activity in SL. The in vitro method allowed us to test this model. We made whole-cell patch-clamp recordings in collicular slices from either rats or GAD67-GFP knock-in mice, in which GABAergic neurons could be identified by their expression of green fluorescence protein (GFP). Antidromic electrical stimulation of SGI premotor cells was produced by applying pulse currents in which their axons congregate after exiting the superior colliculus. The stimulation evoked monosynaptic EPSCs in SGI GABAergic neurons that project to SL, as would be predicted if these neurons receive excitatory input from the premotor cells. Second, IPSCs were evoked in SL neurons, some of which project to the visual thalamus. These IPSCs were polysynaptically mediated by the GABAergic neurons that were excited by the antidromically activated SGI neurons. These results support the hypothesis that collaterals of premotor neuron axons excite GABAergic neurons that inhibit SL visuosensory cells.
Asunto(s)
Modelos Neurológicos , Red Nerviosa/fisiología , Neuronas/fisiología , Movimientos Sacádicos/fisiología , Colículos Superiores/citología , Colículos Superiores/fisiología , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Animales , Animales Modificados Genéticamente , Animales Recién Nacidos , Biofisica , Estimulación Eléctrica/métodos , Antagonistas de Aminoácidos Excitadores/farmacología , Antagonistas del GABA/farmacología , Glutamato Descarboxilasa/genética , Proteínas Fluorescentes Verdes/genética , Técnicas In Vitro , Potenciales Postsinápticos Inhibidores/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/genética , Potenciales de la Membrana/fisiología , Ratones , Ratones Endogámicos C57BL , Técnicas de Placa-Clamp/métodos , Piridazinas/farmacología , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacos , Bloqueadores de los Canales de Sodio/farmacología , Tetrodotoxina/farmacología , Valina/análogos & derivados , Valina/farmacología , Aglutinina del Germen de Trigo-Peroxidasa de Rábano Silvestre Conjugada/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Neurons in the superficial gray layer (SGS) of the superior colliculus receive visual input and excite intermediate layer (SGI) neurons that play a critical role in initiating rapid orienting movements of the eyes, called saccades. In the present study, two types of experiments demonstrate that a population of SGI neurons gives rise to a reciprocal pathway that inhibits neurons in SGS. First, in GAD67-GFP knockin mice, GABAergic SGI neurons that expressed GFP fluorescence were injected with the tracer biocytin to reveal their axonal projections. Axons arising from GFP-positive neurons in SGI terminated densely in SGS. Next, SGI neurons in rats and mice were stimulated by using the photolysis of caged glutamate, and in vitro whole-cell patch-clamp recordings were used to measure the responses evoked in SGS cells. Large, synaptically mediated outward currents were evoked in SGS neurons. These currents were blocked by gabazine, confirming that they were GABA(A) receptor-mediated inhibitory postsynaptic currents. This inhibitory pathway from SGI transiently suppresses visual activity in SGS, which in turn could have multiple effects. These effects could include reduction of perceptual blurring during saccades as well as prevention of eye movements that might be spuriously triggered by the sweep of the visual field across the retina.