Retinal origin of orientation but not direction selective maps in the superior colliculus.

Neurons in the mouse superior colliculus ("colliculus") are arranged in ordered spatial maps. While orientation-selective (OS) neurons form a concentric map aligned to the center of vision, direction-selective (DS) neurons are arranged in patches with changing preferences across the visual field. It remains unclear whether these maps are a consequence of feedforward input from the retina or local computations in the colliculus. To determine whether these maps originate in the retina, we mapped the local and global distribution of OS and DS retinal ganglion cell axon boutons using in vivo two-photon calcium imaging. We found that OS boutons formed patches that matched the distribution of OS neurons within the colliculus. DS boutons displayed fewer regional specializations, better reflecting the organization of DS neurons in the retina. Both eyes convey similar orientation but different DS inputs to the colliculus, as shown in recordings from retinal explants. These data demonstrate that orientation and direction maps within the colliculus are independent, where orientation maps are likely inherited from the retina, but direction maps require additional computations.

Genomic stability of self-inactivating rabies.

Transsynaptic viral vectors provide means to gain genetic access to neurons based on synaptic connectivity and are essential tools for the dissection of neural circuit function. Among them, the retrograde monosynaptic ΔG-Rabies has been widely used in neuroscience research. A recently developed engineered version of the ΔG-Rabies, the non-toxic self-inactivating (SiR) virus, allows the long term genetic manipulation of neural circuits. However, the high mutational rate of the rabies virus poses a risk that mutations targeting the key genetic regulatory element in the SiR genome could emerge and revert it to a canonical ΔG-Rabies. Such revertant mutations have recently been identified in a SiR batch. To address the origin, incidence and relevance of these mutations, we investigated the genomic stability of SiR in vitro and in vivo. We found that "revertant" mutations are rare and accumulate only when SiR is extensively amplified in vitro, particularly in suboptimal production cell lines that have insufficient levels of TEV protease activity. Moreover, we confirmed that SiR-CRE, unlike canonical ΔG-Rab-CRE or revertant-SiR-CRE, is non-toxic and that revertant mutations do not emerge in vivo during long-term experiments.

Collicular circuits supporting the perceptual, motor and cognitive demands of ethological environments.

Animals evolve to survive in their environment. Accordingly, a reasonable hypothesis is that brain evolution prioritises the processing of useful sensory information over complete representation of the surroundings. The superior colliculus or tectum is a brain area that processes the animal's surroundings and directs movements in space. Here, we review recent studies on the role of the superior colliculus to assess the validity of this "utility hypothesis". We discuss how the response properties of collicular neurons vary across anatomical regions to capture ethologically relevant stimuli at a given portion of the sensory field. Next, we focus on the recent advances dissecting the role of defined types of sensory and motor neurons of the colliculus in prey capture. Finally, we discuss the recent literature describing how this ancient structure, with neural circuits over 500 million years old, implements the necessary degree of cognitive control for flexible sensorimotor transformation.

Secreted amyloid-ß precursor protein functions as a GABABR1a ligand to modulate synaptic transmission.

Amyloid-ß precursor protein (APP) is central to the pathogenesis of Alzheimer's disease, yet its physiological function remains unresolved. Accumulating evidence suggests that APP has a synaptic function mediated by an unidentified receptor for secreted APP (sAPP). Here we show that the sAPP extension domain directly bound the sushi 1 domain specific to the γ-aminobutyric acid type B receptor subunit 1a (GABABR1a). sAPP-GABABR1a binding suppressed synaptic transmission and enhanced short-term facilitation in mouse hippocampal synapses via inhibition of synaptic vesicle release. A 17-amino acid peptide corresponding to the GABABR1a binding region within APP suppressed in vivo spontaneous neuronal activity in the hippocampus of anesthetized Thy1-GCaMP6s mice. Our findings identify GABABR1a as a synaptic receptor for sAPP and reveal a physiological role for sAPP in regulating GABABR1a function to modulate synaptic transmission.

Retinotopic Separation of Nasal and Temporal Motion Selectivity in the Mouse Superior Colliculus.

Sensory neurons often display an ordered spatial arrangement that enhances the encoding of specific features on different sides of natural borders in the visual field (for example, [1-3]). In central visual areas, one prominent natural border is formed by the confluence of information from the two eyes, the monocular-binocular border [4]. Here, we investigate whether receptive field properties of neurons in the mouse superior colliculus show any systematic organization about the monocular-binocular border. The superior colliculus is a layered midbrain structure that plays a significant role in the orienting responses of the eye, head, and body [5]. Its superficial layers receive direct input from the majority of retinal ganglion cells and are retinotopically organized [6, 7]. Using two-photon calcium imaging, we recorded the activity of collicular neurons from the superficial layers of awake mice and determined their direction selectivity, orientation selectivity, and retinotopic location. This revealed that nearby direction-selective neurons have a strong tendency to prefer the same motion direction. In retinotopic space, the local preference of direction-selective neurons shows a sharp transition in the preference for nasal versus temporal motion at the monocular-binocular border. The maps representing orientation and direction appear to be independent. These results illustrate the important coherence between the spatial organization of inputs and response properties within the visual system and suggest a re-analysis of the receptive field organization within the superior colliculus from an ecological perspective.