Neuronal computations underlying higher brain functions depend on synaptic interactions among specific neurons. A mechanistic understanding of such computations requires wiring diagrams of neuronal ...networks. In this study, we examined how the olfactory bulb (OB) performs 'whitening', a fundamental computation that decorrelates activity patterns and supports their classification by memory networks. We measured odor-evoked activity in the OB of a zebrafish larva and subsequently reconstructed the complete wiring diagram by volumetric electron microscopy. The resulting functional connectome revealed an over-representation of multisynaptic connectivity motifs that mediate reciprocal inhibition between neurons with similar tuning. This connectivity suppressed redundant responses and was necessary and sufficient to reproduce whitening in simulations. Whitening of odor representations is therefore mediated by higher-order structure in the wiring diagram that is adapted to natural input patterns.
The ability to detect and avoid predators is essential to survival. Various animals, from sea urchins to damselfly larvae, use injury of conspecifics to infer the presence of predators 1–7. In many ...fish 1, 8, 9, skin damage causes the release of chemicals that elicit escape and fear in members of the shoal. The chemical nature of the alarm substance (“Schreckstoff” in German) 1, the neural circuits mediating the complex response, and the evolutionary origins of a signal with little obvious benefit to the sender, are unresolved. To address these questions, we use biochemical fractionation to molecularly characterize Schreckstoff. Although hypoxanthine-3 N-oxide has been proposed to be the alarm substance 10, 11, it has not been reliably detected in the skin 12 and there may be other active components 13, 14. We show that the alarm substance is a mixture that includes the glycosaminoglycan (GAG) chondroitin. Purified chondroitins trigger fear responses. Like skin extract, chondroitins activate the mediodorsal posterior olfactory bulb, a region innervated by crypt neurons 15 that has a unique projection to the habenula 16. These findings establish GAGs as a new class of odorants in fish, which trigger alarm behavior possibly via a specialized circuit.
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► Schreckstoff, the alarm substance in fish, is a mixture ► Chondroitin, a glycosaminoglycan, is a component of the alarm substance ► Skin extract activates the mediodorsal posterior and lateral anterior olfactory bulb ► Purified chondroitin activates the mediodorsal posterior bulb
Neuronal computations critically depend on the connectivity rules that govern the convergence of excitatory and inhibitory synaptic signals onto individual neurons. To examine the functional synaptic ...organization of a distributed memory network, we performed voltage clamp recordings in telencephalic area Dp of adult zebrafish, the homolog of olfactory cortex. In neurons of posterior Dp, odor stimulation evoked large, recurrent excitatory and inhibitory inputs that established a transient state of high conductance and synaptic balance. Excitation and inhibition in individual neurons were co-tuned to different odors and correlated on slow and fast timescales. This precise synaptic balance implies specific connectivity among Dp neurons, despite the absence of an obvious topography. Precise synaptic balance stabilizes activity patterns in different directions of coding space and in time while preserving high bandwidth. The coordinated connectivity of excitatory and inhibitory subnetworks in Dp therefore supports fast recurrent memory operations.
•Odor responses in zebrafish olfactory cortex support a “balanced state”•Synaptic conductances are balanced on fast timescales and in coding space•This implies co-tuning of excitatory and inhibitory synaptic inputs•Precise balance may stabilize memory patterns and support fast classification
Rupprecht and Friedrich find that a transient balanced state is established in the zebrafish homolog of olfactory cortex during an odor response. The balance is maintained on short timescales (tight balance) and in stimulus space (detailed balance) and can stabilize activity patterns in coding space while preserving a high temporal bandwidth.
The main olfactory system encodes information about molecules in a combinatorial fashion by distributed spatiotemporal activity patterns. As activity propagates from sensory neurons to the olfactory ...bulb and to higher brain areas, odor information is processed by multiple transformations of these activity patterns. This review discusses neuronal computations associated with such transformations in the olfactory system of zebrafish, a small vertebrate that offers advantages for the quantitative analysis and manipulation of neuronal activity in the intact brain. The review focuses on pattern decorrelation in the olfactory bulb and on the readout of multiplexed sensory representations in the telencephalic area Dp, the homolog of the olfactory cortex. These computations are difficult to study in larger species and may provide insights into general information-processing strategies in the brain.
In recent years, two-photon calcium imaging has become a standard tool to probe the function of neural circuits and to study computations in neuronal populations. However, the acquired signal is only ...an indirect measurement of neural activity due to the comparatively slow dynamics of fluorescent calcium indicators. Different algorithms for estimating spike rates from noisy calcium measurements have been proposed in the past, but it is an open question how far performance can be improved. Here, we report the results of the spikefinder challenge, launched to catalyze the development of new spike rate inference algorithms through crowd-sourcing. We present ten of the submitted algorithms which show improved performance compared to previously evaluated methods. Interestingly, the top-performing algorithms are based on a wide range of principles from deep neural networks to generative models, yet provide highly correlated estimates of the neural activity. The competition shows that benchmark challenges can drive algorithmic developments in neuroscience.
Inference of action potentials ('spikes') from neuronal calcium signals is complicated by the scarcity of simultaneous measurements of action potentials and calcium signals ('ground truth'). In this ...study, we compiled a large, diverse ground truth database from publicly available and newly performed recordings in zebrafish and mice covering a broad range of calcium indicators, cell types and signal-to-noise ratios, comprising a total of more than 35 recording hours from 298 neurons. We developed an algorithm for spike inference (termed CASCADE) that is based on supervised deep networks, takes advantage of the ground truth database, infers absolute spike rates and outperforms existing model-based algorithms. To optimize performance for unseen imaging data, CASCADE retrains itself by resampling ground truth data to match the respective sampling rate and noise level; therefore, no parameters need to be adjusted by the user. In addition, we developed systematic performance assessments for unseen data, openly released a resource toolbox and provide a user-friendly cloud-based implementation.
The dense reconstruction of neuronal circuits from volumetric electron microscopy (EM) data has the potential to uncover fundamental structure-function relationships in the brain. To address ...bottlenecks in the workflow of this emerging methodology, we developed a procedure for conductive sample embedding and a pipeline for neuron reconstruction. We reconstructed ∼98% of all neurons (>1,000) in the olfactory bulb of a zebrafish larva with high accuracy and annotated all synapses on subsets of neurons representing different types. The organization of the larval olfactory bulb showed marked differences from that of the adult but similarities to that of the insect antennal lobe. Interneurons comprised multiple types but granule cells were rare. Interglomerular projections of interneurons were complex and bidirectional. Projections were not random but biased toward glomerular groups receiving input from common types of sensory neurons. Hence, the interneuron network in the olfactory bulb exhibits a specific topological organization that is governed by glomerular identity.
The categorial nature of sensory, cognitive and behavioural acts indicates that the brain classifies neuronal activity patterns into discrete representations. Pattern classification may be achieved ...by abrupt switching between discrete activity states of neuronal circuits, but few experimental studies have directly tested this. We gradually varied the concentration or molecular identity of odours and optically measured responses across output neurons of the olfactory bulb in zebrafish. Whereas population activity patterns were largely insensitive to changes in odour concentration, morphing of one odour into another resulted in abrupt transitions between odour representations. These transitions were mediated by coordinated response changes among small neuronal ensembles rather than by shifts in the global network state. The olfactory bulb therefore classifies odour-evoked input patterns into many discrete and defined output patterns, as proposed by attractor models. This computation is consistent with perceptual phenomena and may represent a general information processing strategy in the brain.
The function of neuronal networks is determined not only by synaptic connectivity but also by neuromodulatory systems that broadcast information via distributed connections and volume transmission. ...To understand the molecular constraints that organize neuromodulatory signaling in the telencephalon of adult zebrafish, we used transcriptomics and additional approaches to delineate cell types, to determine their phylogenetic conservation, and to map the expression of marker genes at high granularity. The combinatorial expression of GPCRs and cell-type markers indicates that all neuronal cell types are subject to modulation by multiple monoaminergic systems and distinct combinations of neuropeptides. Individual cell types were associated with multiple (typically >30) neuromodulatory signaling networks but expressed only a few diagnostic GPCRs at high levels, suggesting that different neuromodulatory systems act in combination, albeit with unequal weights. These results provide a detailed map of cell types and brain areas in the zebrafish telencephalon, identify core components of neuromodulatory networks, highlight the cell-type specificity of neuropeptides and GPCRs, and begin to decipher the logic of combinatorial neuromodulation.
In this issue of Neuron, Gurnani and Silver (2021) report that activity across Golgi cells, a major type of inhibitory interneuron in the cerebellar cortex, is multidimensional and modulated by ...behavior. These results suggest multiple functions for inhibition in cerebellar computations.
In this issue of Neuron, Gurnani and Silver (2021) report that activity across Golgi cells, a major type of inhibitory interneuron in the cerebellar cortex, is multidimensional and modulated by behavior. These results suggest multiple functions for inhibition in cerebellar computations.
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