Forgetting is important. Without it, the relative importance of acquired memories in a changing environment is lost. We discovered that synaptotagmin-3 (Syt3) localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation. AMPA receptor internalization, long-term depression (LTD), and decay of long-term potentiation (LTP) of synaptic strength required calcium-sensing by Syt3 and were abolished through Syt3 knockout. In spatial memory tasks, mice in which Syt3 was knocked out learned normally but exhibited a lack of forgetting. Disrupting Syt3:GluA2 binding in a wild-type background mimicked the lack of LTP decay and lack of forgetting, and these effects were occluded in the Syt3 knockout background. Our findings provide evidence for a molecular mechanism in which Syt3 internalizes AMPA receptors to depress synaptic strength and promote forgetting.

A retina completely devoid of topographic variations would be homogenous, encoding any given feature uniformly across the visual field. In a naive view, such homogeneity would appear advantageous. However, it is now clear that retinal topographic variations exist across mammalian species in a variety of forms and patterns. We briefly review some of the more established topographic variations in retinas of different mammalian species and focus on the recent discovery that cells belonging to a single neuronal subtype may exhibit distinct topographic variations in distribution, morphology, and even function. We concentrate on the mouse retina—originally viewed as homogenous—in which genetic labeling of distinct neuronal subtypes and other advanced techniques have revealed unexpected anatomical and physiological topographic variations. Notably, different subtypes reveal different patterns of nonuniformity, which may even be opposite or orthogonal to one another. These topographic variations in the encoding of visual space should be considered when studying visual processing in the retina and beyond. Expected final online publication date for the Annual Review of Vision Science, Volume 6 is September 15, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The genome of Drosophila melanogaster includes homologs to approximately one-third of the currently known human disease genes. Flies and humans share many biological processes, including the principles of information processing by excitable neurons, synaptic transmission, and the chemical signals involved in intercellular communication. Studies on the molecular and behavioral impact of genetic risk factors of human neuro-developmental disorders [autism spectrum disorders (ASDs), schizophrenia, attention deficit hyperactivity disorders, and Tourette syndrome] increasingly use the well-studied social behavior of D. melanogaster, an organism that is amenable to a large variety of genetic manipulations. Neuroligins (Nlgs) are a family of phylogenetically conserved postsynaptic adhesion molecules present (among others) in nematodes, insects, and mammals. Impaired function of Nlgs (particularly of Nlg 3 and 4) has been associated with ASDs in humans and impaired social and communication behavior in mice. Making use of a set of behavioral and social assays, we, here, analyzed the impact of two Drosophila Nlgs, Dnlg2 and Dnlg4, which are differentially expressed at excitatory and inhibitory central nervous synapses, respectively. Both Nlgs seem to be associated with diurnal activity and social behavior. Even though deficiencies in Dnlg2 and Dnlg4 appeared to have no effects on sensory or motor systems, they differentially impacted on social interactions, suggesting that social behavior is distinctly regulated by these Nlgs.

SummaryThe mammalian retina is considered an autonomous circuit, yet work dating back to Ramon y Cajal indicates that it receives inputs from the brain. How such inputs affect retinal processing has remained unknown. We identified brain-to-retina projections of histaminergic neurons from the mouse hypothalamus, which densely innervated the dorsal retina. Histamine application, or chemogenetic activation of histaminergic axons, altered spontaneous and light-evoked activity of various retinal ganglion cells (RGCs), including direction-selective RGCs. These cells exhibited broader directional tuning and gained responses to high motion velocities. Such changes could improve vision when objects move fast across the visual field (e.g. while running), which fits with the known increased activity of histaminergic neurons during arousal. In humans, an antihistamine drug non-uniformly modulated visual sensitivity across the visual field, indicating an evolutionary conserved function of the histaminergic system. Our findings expose a previously unappreciated role for brain-to-retina projections in modulating retinal function.

Dopamine has long been reported to enhance antagonistic surrounds of retinal ganglion cells (RGCs). Yet, the retina contains many different RGC subtypes and the effects of dopamine can be subtype‐specific. Using multielectrode array (MEA) recordings we investigated how dopamine shapes the receptive fields of RGCs in the mouse retina. We found that the non‐selective dopamine receptor agonist apomorphine can either increase or decrease RGCs’ surround strength, depending on their subtype. We then used two‐photon targeted patch‐clamp to target a specific RGC subtype, the transient‐Off‐αRGC. In line with our MEA recordings, apomorphine did not increase the antagonistic surround of transient‐Off‐αRGCs but enhanced their responses to Off stimuli in the centre receptive field. Both D1‐ and D2‐like family receptor (D1‐R and D2‐R) blockers had the opposite effect and reduced centre‐mediated responses, but differently affected transient‐Off‐αRGC's surround. While D2‐R blocker reduced surround antagonism, D1‐R blocker led to surround activation, revealing On responses to large stimuli. Using voltage‐clamp recordings we separated excitatory inputs from Off cone bipolar cells and inhibitory inputs from the primary rod pathway. In control conditions, cone inputs displayed strong surround antagonism, while inputs from the primary rod pathway showed no surround. Yet, the surround activation in the D1‐R blockade originated from the primary rod pathway. Our findings demonstrate that dopamine differentially affects RGC subtypes via distinct pathways, suggesting that dopamine has a more complex role in shaping the retinal code than previously reported. Key points Receptive fields of retinal ganglion cells (RGCs) have a centre–surround organisation, and previous work has shown that this organisation can be modulated by dopamine in a light‐intensity‐dependent manner. Dopamine is thought to enhance RGCs’ antagonistic surround, but a detailed understanding of how different RGC subtypes are affected is missing. Using a multielectrode array recordings, clustering analysis and pharmacological manipulations, we found that dopamine can either enhance or weaken antagonistic surrounds, and also change response kinetics, of RGCs in a subtype‐specific manner. We performed targeted patch‐clamp recordings of one RGC subtype, the transient‐Off‐αRGC, and identified the underlying circuits by which dopamine shapes its receptive field. Our findings demonstrate that dopamine acts in a subtype‐specific manner and can have complex effects, which has implications for other retinal computations that rely on receptive field structure.