Before the onset of sensory transduction, developing neural circuits spontaneously generate correlated activity in distinct spatial and temporal patterns. During this period of patterned activity, sensory maps develop and initial coarse connections are refined, which are critical steps in the establishment of adult neural circuits. Over the last decade there has been substantial evidence that altering the pattern of spontaneous activity disrupts refinement, but the mechanistic understanding of this process remains incomplete. In this review, we discuss recent experimental and theoretical progress towards the process of activity-dependent refinement, focusing on circuits in the visual, auditory and motor systems. While many outstanding questions remain, the combination of several novel approaches have brought us closer to a comprehensive understanding of how complex neural circuits are established by patterned spontaneous activity during development.

The formation of precise connections between retina and LGN involves the activity-dependent elimination of some synapses, with strengthening and retention of others. Here we show that the MHC Class I (MHCI) molecule H2-Db is necessary and sufficient for synapse elimination in the retinogeniculate system. In mice lacking both H2-Kb and H2-Db (KbDb−/−) despite intact retinal activity and basal synaptic transmission, the developmentally-regulated decrease in functional convergence of retinal ganglion cell synaptic inputs to LGN neurons fails and eye-specific layers do not form. Neuronal expression of just H2-Db in KbDb−/− mice rescues both synapse elimination and eye specific segregation despite a compromised immune system. When patterns of stimulation mimicking endogenous retinal waves are used to probe synaptic learning rules at retinogeniculate synapses, LTP is intact but LTD is impaired in KbDb−/− mice. This change is due to an increase in Ca2+ permeable AMPA receptors. Restoring H2-Db to KbDb−/− neurons renders AMPA receptors Ca2+ impermeable and rescues LTD. These observations reveal an MHCI mediated link between developmental synapse pruning and balanced synaptic learning rules enabling both LTD and LTP, and demonstrate a direct requirement for H2-Db in functional and structural synapse pruning in CNS neurons.

Graphical Abstract Highlights d Coordinated changes in coherence reveal conserved networks within the human brain d A network defined by amygdala-hippocampus b-coherence predicts mood in 13 of 21 subjects d Increased variability of coherence within this network predicts worse mood d Subjects with higher baseline anxiety consistently have this mood-predictive network

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Before the maturation of rod and cone photoreceptors, the developing retina relies on light detection by intrinsically photosensitive retinal ganglion cells (ipRGCs) to drive early light-dependent behaviors. ipRGCs are output neurons of the retina; however, they also form functional microcircuits within the retina itself. Whether ipRGC microcircuits exist during development and whether they influence early light detection remain unknown. Here, we investigate the neural circuit that underlies the ipRGC-driven light response in developing mice. We use a combination of calcium imaging, tracer coupling, and electrophysiology experiments to show that ipRGCs form extensive gap junction networks that strongly contribute to the overall light response of the developing retina. Interestingly, we found that gap junction coupling was modulated by spontaneous retinal waves, such that acute blockade of waves dramatically increased the extent of coupling and hence increased the number of light-responsive neurons. Moreover, using an optical sensor, we found that this wavedependent modulation of coupling is driven by dopamine that is phasically released by retinal waves. Our results demonstrate that ipRGCs form gap junction microcircuits during development that are modulated by retinal waves; these circuits determine the extent of the light response and thus potentially impact the processing of early visual information and light-dependent developmental functions.