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, 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.
Animal behaviour arises from computations in neuronal circuits, but our understanding of these computations has been frustrated by the lack of detailed synaptic connection maps, or connectomes. For ...example, despite intensive investigations over half a century, the neuronal implementation of local motion detection in the insect visual system remains elusive. Here we develop a semi-automated pipeline using electron microscopy to reconstruct a connectome, containing 379 neurons and 8,637 chemical synaptic contacts, within the Drosophila optic medulla. By matching reconstructed neurons to examples from light microscopy, we assigned neurons to cell types and assembled a connectome of the repeating module of the medulla. Within this module, we identified cell types constituting a motion detection circuit, and showed that the connections onto individual motion-sensitive neurons in this circuit were consistent with their direction selectivity. Our results identify cellular targets for future functional investigations, and demonstrate that connectomes can provide key insights into neuronal computations.
Sensory experience remodels neural circuits in the early postnatal brain through mechanisms that remain to be elucidated. Applying a new method of ultrastructural analysis to the retinogeniculate ...circuit, we find that visual experience alters the number and structure of synapses between the retina and the thalamus. These changes require vision-dependent transcription of the receptor Fn14 in thalamic relay neurons and the induction of its ligand TWEAK in microglia. Fn14 functions to increase the number of bulbous spine-associated synapses at retinogeniculate connections, likely contributing to the strengthening of the circuit that occurs in response to visual experience. However, at retinogeniculate connections near TWEAK-expressing microglia, TWEAK signals via Fn14 to restrict the number of bulbous spines on relay neurons, leading to the elimination of a subset of connections. Thus, TWEAK and Fn14 represent an intercellular signaling axis through which microglia shape retinogeniculate connectivity in response to sensory experience.
Display omitted
•Experience induces Fn14 expression in neurons and TWEAK expression in microglia•Fn14 increases the number of spine-associated synapses when not bound by TWEAK•Microglial TWEAK signals through neuronal Fn14 to locally decrease synapse numbers•Microglia-driven synapse loss occurs through a non-phagocytic mechanism
Sensory experience induces Fn14 expression in relay neurons and TWEAK expression in microglia to drive refinement of retinogeniculate connectivity. Microglial TWEAK signals through neuronal Fn14 to eliminate a subset of synapses proximal to TWEAK-expressing microglia, whereas Fn14 acts alone at other synapses to strengthen connectivity.
Vision is the sense humans rely on most to navigate the world, make decisions, and perform complex tasks. Understanding how humans see thus represents one of the most fundamental and important goals ...of neuroscience. The use of the mouse as a model for parsing how vision works at a fundamental level started approximately a decade ago, ushered in by the mouse's convenient size, relatively low cost, and, above all, amenability to genetic perturbations. In the course of that effort, a large cadre of new and powerful tools for in vivo labeling, monitoring, and manipulation of neurons were applied to this species. As a consequence, a significant body of work now exists on the architecture, function, and development of mouse central visual pathways. Excitingly, much of that work includes causal testing of the role of specific cell types and circuits in visual perception and behavior-something rare to find in studies of the visual system of other species. Indeed, one could argue that more information is now available about the mouse visual system than any other sensory system, in any species, including humans. As such, the mouse visual system has become a platform for multilevel analysis of the mammalian central nervous system generally. Here we review the mouse visual system structure, function, and development literature and comment on the similarities and differences between the visual system of this and other model species. We also make it a point to highlight the aspects of mouse visual circuitry that remain opaque and that are in need of additional experimentation to enrich our understanding of how vision works on a broad scale.
Two main subcortical pathways serving conscious visual perception are the midget-parvocellular (P), and the parasol-magnocellular (M) pathways. It is generally accepted that the P pathway serves ...red-green color vision, but the relative contribution of P and M pathways to spatial vision is a long-standing and unresolved issue. Here, we mapped the spatial sampling properties of P and M pathways across the human retina. Data were obtained from immunolabeled vertical sections of six postmortem male and female human donor retinas and imaged using high-resolution microscopy. Cone photoreceptors, OFF-midget bipolar cells (P pathway), OFF-diffuse bipolar (DB) types DB3a and DB3b (M pathway), and ganglion cells were counted along the temporal horizontal meridian, taking foveal spatial distortions (postreceptoral displacements) into account. We found that the density of OFF-midget bipolar and OFF-midget ganglion cells can support one-to-one connections to 1.05-mm (3.6°) eccentricity. One-to-one connections of cones to OFF-midget bipolar cells are present to at least 10-mm (35°) eccentricity. The OFF-midget ganglion cell array acuity is well-matched to photopic spatial acuity measures throughout the central 35°, but the OFF-parasol array acuity is well below photopic spatial acuity, supporting the view that the P pathway underlies high-acuity spatial vision. Outside the fovea, array acuity of both OFF-midget and OFF-DB cells exceeds psychophysical measures of photopic spatial acuity. We conclude that parasol and midget pathway bipolar cells deliver high-acuity spatial signals to the inner plexiform layer, but outside the fovea, this spatial resolution is lost at the level of ganglion cells.
We make accurate maps of the spatial density and distribution of neurons in the human retina to aid in understanding human spatial vision, interpretation of diagnostic tests, and the implementation of therapies for retinal diseases. Here, we map neurons involved with the midget-parvocellular (P pathway) and parasol-magnocellular (M pathway) through human retina. We find that P-type bipolar cells outnumber M-type bipolar cells at all eccentricities. We show that cone photoreceptors and P-type pathway bipolar cells are tightly connected throughout the retina, but that spatial resolution is lost at the level of the ganglion cells. Overall, the results support the view that the P pathway is specialized to serve both high acuity vision and red-green color vision.
The division of cortical visual processing into distinct dorsal and ventral streams is a key framework that has guided visual neuroscience. The characterization of the ventral stream as a 'What' ...pathway is relatively uncontroversial, but the nature of dorsal stream processing is less clear. Originally proposed as mediating spatial perception ('Where'), more recent accounts suggest it primarily serves non-conscious visually guided action ('How'). Here, we identify three pathways emerging from the dorsal stream that consist of projections to the prefrontal and premotor cortices, and a major projection to the medial temporal lobe that courses both directly and indirectly through the posterior cingulate and retrosplenial cortices. These three pathways support both conscious and non-conscious visuospatial processing, including spatial working memory, visually guided action and navigation, respectively.
Since the original characterization of the ventral visual pathway, our knowledge of its neuroanatomy, functional properties, and extrinsic targets has grown considerably. Here we synthesize this ...recent evidence and propose that the ventral pathway is best understood as a recurrent occipitotemporal network containing neural representations of object quality both utilized and constrained by at least six distinct cortical and subcortical systems. Each system serves its own specialized behavioral, cognitive, or affective function, collectively providing the raison d’être for the ventral visual pathway. This expanded framework contrasts with the depiction of the ventral visual pathway as a largely serial staged hierarchy culminating in singular object representations and more parsimoniously incorporates attentional, contextual, and feedback effects.
Stereotyped synaptic connections define the neural circuits of the brain. In vertebrates, stimulus-independent activity contributes to neural circuit formation. It is unknown whether this type of ...activity is a general feature of nervous system development. Here, we report patterned, stimulus-independent neural activity in the Drosophila visual system during synaptogenesis. Using in vivo calcium, voltage, and glutamate imaging, we found that all neurons participate in this spontaneous activity, which is characterized by brain-wide periodic active and silent phases. Glia are active in a complementary pattern. Each of the 15 of over 100 specific neuron types in the fly visual system examined exhibited a unique activity signature. The activity of neurons that are synaptic partners in the adult was highly correlated during development. We propose that this cell-type-specific activity coordinates the development of the functional circuitry of the adult brain.
•Stimulus-independent neural activity occurs in the developing Drosophila visual system•Cell types exhibit unique activity patterns within a common oscillatory structure•Activity patterns reflect adult connectivity in the ON and OFF motion circuits
Akin and Bajar et al. report that stimulus-independent neural activity occurs in cell-type-specific patterns during synapse formation in Drosophila. Their findings suggest that neural activity may be a fundamental feature of brain development.
The dorsal and ventral visual pathways represent both visual and conceptual object properties. Yet the relative contribution of these two factors in the representational content of visual areas is ...unclear. Indeed, research investigating brain category representations rarely dissociate visual and semantic properties of objects. We present a human event-related fMRI study with a two-factorial stimulus set with 54 images that explicitly dissociates shape from category to investigate their independent contribution as well as their interactions through representational similarity analyses. Results reveal a contribution from each dimension in both streams, with a transition from shape to category along the posterior-to-anterior anatomical axis. The nature of category representations differs in the two pathways: ventral areas represent object animacy and dorsal areas represent object action properties. Furthermore, information about shape evolved from low-level pixel-based to high-level perceived shape following a posterior-to-anterior gradient similar to the shape-to-category emergence. To conclude, results show that representations of shape and category independently coexist, but at the same time they are closely related throughout the visual hierarchy.
Research investigating visual cortex conceptual category representations rarely takes into account visual properties of objects. In this report, we explicitly dissociate shape from category and investigate independent contributions and interactions of these two highly correlated dimensions.
A balance between synaptic excitation and inhibition (E/I balance) maintained within a narrow window is widely regarded to be crucial for cortical processing. In line with this idea, the E/I balance ...is reportedly comparable across neighboring neurons, behavioral states, and developmental stages and altered in many neurological disorders. Motivated by these ideas, we examined whether synaptic inhibition changes over the 24-h day to compensate for the well-documented sleep-dependent changes in synaptic excitation. We found that, in pyramidal cells of visual and prefrontal cortices and hippocampal CA1, synaptic inhibition also changes over the 24-h light/dark cycle but, surprisingly, in the opposite direction of synaptic excitation. Inhibition is upregulated in the visual cortex during the light phase in a sleep-dependent manner. In the visual cortex, these changes in the E/I balance occurred in feedback, but not feedforward, circuits. These observations open new and interesting questions on the function and regulation of the E/I balance.
•The excitation/inhibition (E/I) ratio is dynamic across the 24-h day•Fluctuations in the E/I ratio depend on sleep/wake history•E/I ratio changes are circuit specific, not uniform across all synapses
Bridi et al. investigate whether inhibition tracks known changes in excitation over the 24-h day to maintain a stable excitation/inhibition ratio. Surprisingly, the excitation/inhibition ratio is dynamic over the day in feedback, but not feedforward, visual cortical circuits.
PDF
