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Two-photon calcium imaging and electron microscopy were used to explore the relationship between structure and function in mouse primary visual cortex, showing that layer 2/3 neurons are connected in subnetworks, that pyramidal neurons with similar orientation selectivity preferentially form synapses with each other, and that neurons with similar orientation tuning form larger synapses; this study exemplifies functional connectomics as a powerful method for studying the organizational logic of cortical networks. The connectomics of excitatory cortical networks To explore the relationship between structure and function in cortical networks, Wei-Chung Allen Lee and colleagues combined two-photon calcium imaging and electron microscopy in mouse primary visual cortex. They found that layer 2/3 neurons are organized into subnetworks, that pyramidal neurons with similar orientation selectivity preferentially form synapses with each other, and that neurons with similar orientation tuning form larger synapses. This study exemplifies functional connectomics as a powerful method for studying the organizational logic of cortical networks. Circuits in the cerebral cortex consist of thousands of neurons connected by millions of synapses. A precise understanding of these local networks requires relating circuit activity with the underlying network structure. For pyramidal cells in superficial mouse visual cortex (V1), a consensus is emerging that neurons with similar visual response properties excite each other 1 , 2 , 3 , 4 , 5 , but the anatomical basis of this recurrent synaptic network is unknown. Here we combined physiological imaging and large-scale electron microscopy to study an excitatory network in V1. We found that layer 2/3 neurons organized into subnetworks defined by anatomical connectivity, with more connections within than between groups. More specifically, we found that pyramidal neurons with similar orientation selectivity preferentially formed synapses with each other, despite the fact that axons and dendrites of all orientation selectivities pass near (<5 μm) each other with roughly equal probability. Therefore, we predict that mechanisms of functionally specific connectivity take place at the length scale of spines. Neurons with similar orientation tuning formed larger synapses, potentially enhancing the net effect of synaptic specificity. With the ability to study thousands of connections in a single circuit, functional connectomics is proving a powerful method to uncover the organizational logic of cortical networks.

Many animals use visual information to navigate 1 – 4 , but how such information is encoded and integrated by the navigation system remains incompletely understood. In Drosophila melanogaster , EPG neurons in the central complex compute the heading direction 5 by integrating visual input from ER neurons 6 – 12 , which are part of the anterior visual pathway (AVP) 10 , 13 – 16 . Here we densely reconstruct all neurons in the AVP using electron-microscopy data 17 . The AVP comprises four neuropils, sequentially linked by three major classes of neurons: MeTu neurons 10 , 14 , 15 , which connect the medulla in the optic lobe to the small unit of the anterior optic tubercle (AOTUsu) in the central brain; TuBu neurons 9 , 16 , which connect the AOTUsu to the bulb neuropil; and ER neurons 6 – 12 , which connect the bulb to the EPG neurons. On the basis of morphologies, connectivity between neural classes and the locations of synapses, we identify distinct information channels that originate from four types of MeTu neurons, and we further divide these into ten subtypes according to the presynaptic connections in the medulla and the postsynaptic connections in the AOTUsu. Using the connectivity of the entire AVP and the dendritic fields of the MeTu neurons in the optic lobes, we infer potential visual features and the visual area from which any ER neuron receives input. We confirm some of these predictions physiologically. These results provide a strong foundation for understanding how distinct sensory features can be extracted and transformed across multiple processing stages to construct higher-order cognitive representations. Electron-microscopy data are used to reconstruct the neurons that make up the anterior visual pathway in the Drosophila brain, providing insight into how visual features are encoded to guide navigation.

Social affiliation emerges from individual-level behavioural rules that are driven by conspecific signals 1 – 5 . Long-distance attraction and short-distance repulsion, for example, are rules that jointly set a preferred interanimal distance in swarms 6 – 8 . However, little is known about their perceptual mechanisms and executive neural circuits 3 . Here we trace the neuronal response to self-like biological motion 9 , 10 , a visual trigger for affiliation in developing zebrafish 2 , 11 . Unbiased activity mapping and targeted volumetric two-photon calcium imaging revealed 21 activity hotspots distributed throughout the brain as well as clustered biological-motion-tuned neurons in a multimodal, socially activated nucleus of the dorsal thalamus. Individual dorsal thalamus neurons encode local acceleration of visual stimuli mimicking typical fish kinetics but are insensitive to global or continuous motion. Electron microscopic reconstruction of dorsal thalamus neurons revealed synaptic input from the optic tectum and projections into hypothalamic areas with conserved social function 12 – 14 . Ablation of the optic tectum or dorsal thalamus selectively disrupted social attraction without affecting short-distance repulsion. This tectothalamic pathway thus serves visual recognition of conspecifics, and dissociates neuronal control of attraction from repulsion during social affiliation, revealing a circuit underpinning collective behaviour. A tectothalamic pathway for social affiliation in developing zebrafish dissociates neuronal control of attraction from repulsion during affiliation, revealing a circuit underpinning of collective behaviour

The authors used two-photon imaging to measure the orientation tuning of thalamic boutons and neurons in mouse V1. They found that a smaller fraction of thalamic boutons in layer 4 than in superficial cortical layers carried orientation and direction information. It has been debated whether orientation selectivity in mouse primary visual cortex (V1) is derived from tuned lateral geniculate nucleus (LGN) inputs or computed from untuned LGN inputs. However, few studies have measured orientation tuning of LGN axons projecting to V1. We measured the response properties of mouse LGN axons terminating in V1 and found that LGN axons projecting to layer 4 were generally less tuned for orientation than axons projecting to more superficial layers of V1. We also found several differences in response properties between LGN axons and V1 neurons in layer 4. These results suggest that orientation selectivity of mouse V1 may not simply be inherited from LGN inputs, but could also depend on thalamocortical or V1 circuits.

Midbrain dopaminergic neurons respond to unexpected and biologically salient events, but little is known about the sensory systems underlying this response. Here we describe, in the rat, a direct projection from a primary visual structure, the midbrain superior colliculus (SC), to the substantia nigra pars compacta (SNc) where direct synaptic contacts are made with both dopaminergic and non-dopaminergic neurons. Complementary electrophysiological data reveal that short-latency visual responses in the SNc are abolished by ipsilateral lesions of the SC and increased by local collicular stimulation. These results show that the tectonigral projection is ideally located to relay short-latency visual information to dopamine-containing regions of the ventral midbrain. We conclude that it is within this afferent sensory circuitry that the critical perceptual discriminations that identify stimuli as both unpredicted and biologically salient are made.

The authors combine electrophysiology, calcium imaging and immunohistochemistry to show that L-type Ca v channels in rat A17 amacrine cells are well placed to mediate reciprocal inhibitory feedback to rod bipolar cells. However, they find that the contribution of these channels to GABA release is diminished by large-conductance Ca 2+ -activated potassium (BK) channels, which suppress postsynaptic depolarization in A17s and limit Ca v channel activation. In the mammalian retina, A17 amacrine cells provide reciprocal inhibitory feedback to rod bipolar cells, thereby shaping the time course of visual signaling in vivo . Previous results have indicated that A17 feedback can be triggered by Ca 2+ influx through Ca 2+ -permeable AMPA receptors and can occur independently of voltage-gated Ca 2+ (Ca v ) channels, whose presence and functional role in A17 dendrites have not yet been explored. We combined electrophysiology, calcium imaging and immunohistochemistry and found that L-type Ca v channels in rat A17 amacrine cells were located at the sites of reciprocal synaptic feedback and that their contribution to GABA release was diminished by large-conductance Ca 2+ -activated potassium (BK) channels, which suppress postsynaptic depolarization in A17s and limit Ca v channel activation. We also found that BK channels, by limiting GABA release from A17s, regulate the flow of excitatory synaptic transmission through the rod pathway.

Purpose This study assessed whether optic radiations (OR) microstructure after temporal lobe epilepsy (TLE) surgery correlated with visual field defects (VFD). Methods Patients were subjected to diffusion tensor imaging (DTI) tractography of the OR and Humphrey perimetry after TLE surgery. We used Spearman’s test to verify correlations between tractographic parameters and perimetry mean deviation. Tractographic variables were compared between patients with VFD or intact perimetry. Multiple logistic regression was applied between DTI and perimetry values. DTI sensitivity and specificity were assessed with a receiver operating characteristic (ROC) curve to evaluate VFD. Results Thirty-nine patients had reliable perimetry and OR tractography. There was a significant correlation between (1) fractional anisotropy (FA) and both total (rho = 0.569, p  = 0.0002) and quadrant (rho = 0.453, p  = 0.0037) mean deviation and (2) radial diffusivity and total mean deviation (rho = − 0.350, p  = 0.0286). There was no other significant correlation. Patients with VFD showed a significantly lower FA compared with patients with normal perimetry ( p  = 0.0055), and a 0.01 reduction in FA was associated with a 44% increase in presenting VFD after surgery (confidence interval, CI = 1.10–1.88; p  = 0.0082). Using a FA of 0.457, DTI tractography showed a specificity of 95.2% and a sensitivity of 50% to detect VFD after surgery (area under the curve = 0.7619, CI = 0.6020–0.9218). Conclusion The postoperative OR microstructure correlated with visual loss after epilepsy surgery. DTI postoperative OR tractography may be helpful in evaluating VFD.

Rod photoreceptors contact Off cone bipolar cells, but it has been unclear what the function of this pathway is. The authors recorded from pairs of rods and Off cone bipolar cells in the ground squirrel and show that this new pathway can mediate rapid signaling in the retina. Rod photoreceptors were recently shown to contact 'Off' cone bipolar cells, providing an alternative pathway for rod signal flow in the mammalian retina. By recording from pairs of rods and Off cone bipolar cells in the ground squirrel ( Spermophilus tridecemlineatus ), we measured the synaptic responses of mammalian rods unfiltered by the slow kinetics of the rod bipolar cell response. We show that vesicle fusion and turnover in mammalian rods is fast, and that this new pathway can mediate rapid signaling.

Photoreceptor neurons (R cells) in the Drosophila visual system elaborate a precise map of visual space in the brain. The eye contains some 750 identical modules called ommatidia, each containing eight photoreceptor cells (R1–R8). Cells R1–R6 synapse in the lamina; R7 and R8 extend through the lamina and terminate in the underlying medulla. In a screen for visual behavior mutants, we identified alleles of flamingo ( fmi ) that disrupt the precise maps elaborated by these neurons. These mutant R1–R6 neurons select spatially inappropriate targets in the lamina. During target selection, Flamingo protein is dynamically expressed in R1–R6 growth cones. Loss of fmi function in R cells also disrupts the local pattern of synaptic terminals in the medulla, and Flamingo is transiently expressed in R8 axons as they enter the target region. We propose that Flamingo-mediated interactions between R-cell growth cones within the target field regulate target selection.

Doc number: 16 Abstract Background: Mouse visual thalamus has emerged as a powerful model for understanding the mechanisms underlying neural circuit formation and function. Three distinct nuclei within mouse thalamus receive retinal input, the dorsal lateral geniculate nucleus (dLGN), the ventral lateral geniculate nucleus (vLGN), and the intergeniculate nucleus (IGL). However, in each of these nuclei, retinal inputs are vastly outnumbered by nonretinal inputs that arise from cortical and subcortical sources. Although retinal and nonretinal terminals associated within dLGN circuitry have been well characterized, we know little about nerve terminal organization, distribution and development in other nuclei of mouse visual thalamus. Results: Immunolabeling specific subsets of synapses with antibodies against vesicle-associated neurotransmitter transporters or neurotransmitter synthesizing enzymes revealed significant differences in the composition, distribution and morphology of nonretinal terminals in dLGN, vLGN and IGL. For example, inhibitory terminals are more densely packed in vLGN, and cortical terminals are more densely distributed in dLGN. Overall, synaptic terminal density appears least dense in IGL. Similar nuclei-specific differences were observed for retinal terminals using immunolabeling, genetic labeling, axonal tracing and serial block face scanning electron microscopy: retinal terminals are smaller, less morphologically complex, and more densely distributed in vLGN than in dLGN. Since glutamatergic terminal size often correlates with synaptic function, we used in vitro whole cell recordings and optic tract stimulation in acutely prepared thalamic slices to reveal that excitatory postsynaptic currents (EPSCs) are considerably smaller in vLGN and show distinct responses following paired stimuli. Finally, anterograde labeling of retinal terminals throughout early postnatal development revealed that anatomical differences in retinal nerve terminal structure are not observable as synapses initially formed, but rather developed as retinogeniculate circuits mature. Conclusions: Taken together, these results reveal nuclei-specific differences in nerve terminal composition, distribution, and morphology in mouse visual thalamus. These results raise intriguing questions about the different functions of these nuclei in processing light-derived information, as well as differences in the mechanisms that underlie their unique, nuclei-specific development.