Types Of Neurons Research Articles

Distinct Neuron Types Contribute to Hybrid Auditory Spatial Coding.

Neural decoding is a tool for understanding how activities from a population of neurons inside the brain relate to the outside world and for engineering applications such as brain-machine interfaces. However, neural decoding studies mainly focused on different decoding algorithms rather than different neuron types which could use different coding strategies. In this study, we used two-photon calcium imaging to assess three auditory spatial decoders (space map, opponent channel, and population pattern) in excitatory and inhibitory neurons in the dorsal inferior colliculus of male and female mice. Our findings revealed a clustering of excitatory neurons that prefer similar interaural level difference (ILD), the primary spatial cues in mice, while inhibitory neurons showed random local ILD organization. We found that inhibitory neurons displayed lower decoding variability under the opponent channel decoder, while excitatory neurons achieved higher decoding accuracy under the space map and population pattern decoders. Further analysis revealed that the inhibitory neurons' preference for ILD off the midline and the excitatory neurons' heterogeneous ILD tuning account for their decoding differences. Additionally, we discovered a sharper ILD tuning in the inhibitory neurons. Our computational model, linking this to increased presynaptic inhibitory inputs, was corroborated using monaural and binaural stimuli. Overall, this study provides experimental and computational insight into how excitatory and inhibitory neurons uniquely contribute to the coding of sound locations.

Photoinduced Online Enrichment-Deglycosylation of Glycolipids for Enhancing Lipid Coverage and Identification in Single-Cell Mass Spectrometry.

Single-cell lipidomics provides important information for molecular mechanisms of living processes and diseases at the individual cell level. However, single-cell lipidomic mass spectrometry (MS) techniques suffer from low lipid coverage and incomplete structural elucidation, especially for poorly ionizable glycosphingolipids (GSLs). Herein, a photoinduced enrichment-deglycosylation method of GSLs was developed and introduced into an ambient liquid extraction MS system for enhancing detection coverage and identification accuracy of GSLs in single-cell MS. GSL standards were selectively adsorbed on TiO2 in ammonia-added protic solvents. Under UV irradiation, the adsorbed GSLs would lose one hexosyl group (deglycosylation), and the products (>70% conversion efficiency) were desorbed from TiO2. By coating porous TiO2 into the capillary of the ambient liquid extraction MS system, online adsorption of GSLs and their separation from high-abundance phospholipids were achieved, largely reducing ion suppression. By UV irradiation, captured GSLs were rapidly deglycosylated and photodesorbed from TiO2 coating without solvent switching, resulting in 6-fold enrichment. With the new method, the detection coverage of GSLs was enhanced 9-fold without losing other lipidomes, compared with the conventional method. Moreover, deglycosylated GSLs from photodesorption had more MS/MS fragments than intact GSLs, facilitating detailed fatty acyl and sphingosine chain elucidation. Seven deglycosylated GSL peaks were identified with the confirmed hydroxyl group location in the fatty acyl chain, while only 1 was identified for intact GSL. The new method was applied to the single-cell lipidomics study of two types of nerve cells. Totally, 31 lipids including 11 GSLs were identified in a single cell, and 5 hexosylceramides were found significantly altered after neuron injury.

Celsr3 drives development and connectivity of the acoustic startle hindbrain circuit.

In the developing brain, groups of neurons organize into functional circuits that direct diverse behaviors. One such behavior is the evolutionarily conserved acoustic startle response, which in zebrafish is mediated by a well-defined hindbrain circuit. While numerous molecular pathways that guide neurons to their synaptic partners have been identified, it is unclear if and to what extent distinct neuron populations in the startle circuit utilize shared molecular pathways to ensure coordinated development. Here, we show that the planar cell polarity (PCP)-associated atypical cadherins Celsr3 and Celsr2, as well as the Celsr binding partner Frizzled 3a/Fzd3a, are critical for axon guidance of two neuron types that form synapses with each other: the command-like neuron Mauthner cells that drive the acoustic startle escape response, and spiral fiber neurons which provide excitatory input to Mauthner cells. We find that Mauthner axon growth towards synaptic targets is vital for Mauthner survival. We also demonstrate that symmetric spiral fiber input to Mauthner cells is critical for escape direction, which is necessary to respond to directional threats. Moreover, we identify distinct roles for Celsr3 and Celsr2, as Celsr3 is required for startle circuit development while Celsr2 is dispensable, though Celsr2 can partially compensate for loss of Celsr3 in Mauthner cells. This contrasts with facial branchiomotor neuron migration in the hindbrain, which requires Celsr2 while we find that Celsr3 is dispensable. Combined, our data uncover critical and distinct roles for individual PCP components during assembly of the acoustic startle hindbrain circuit.

Increased understanding of complex neuronal circuits in the cerebellar cortex

The prevailing belief has been that the fundamental structures of cerebellar neuronal circuits, consisting of a few major neuron types, are simple and well understood. Given that the cerebellum has long been known to be crucial for motor behaviors, these simple yet organized circuit structures seemed beneficial for theoretical studies proposing neural mechanisms underlying cerebellar motor functions and learning. On the other hand, experimental studies using advanced techniques have revealed numerous structural properties that were not traditionally defined. These include subdivided neuronal types and their circuit structures, feedback pathways from output Purkinje cells, and the multidimensional organization of neuronal interactions. With the recent recognition of the cerebellar involvement in non-motor functions, it is possible that these newly identified structural properties, which are potentially capable of generating greater complexity than previously recognized, are associated with increased information capacity. This, in turn, could contribute to the wide range of cerebellar functions. However, it remains largely unknown how such structural properties contribute to cerebellar neural computations through the regulation of neuronal activity or synaptic transmissions. To promote further research into cerebellar circuit structures and their functional significance, we aim to summarize the newly identified structural properties of the cerebellar cortex and discuss future research directions concerning cerebellar circuit structures and their potential functions.

Thalamus of Reptiles and Mammals: Some Significant Differences.

Most studies comparing forebrain organization between reptiles and mammals have focused on similarities. Equally important are the differences between their brains. While differences have been addressed infrequently, this approach can highlight the evolution of brains in relation to their respective environments. This review focuses on three key differences between the dorsal and ventral thalamus of reptiles and mammals. One is the organization of thalamo-telencephalic interconnections. Reptiles have at least three circuits that transmit information between the dorsal thalamus and telencephalon whereas mammals have just one. A second is the number and distribution of local circuit neurons in the dorsal thalamus. Most reptilian dorsal thalamic nuclei lack local circuit neurons whereas these same nuclei in mammals contain varying numbers. The third is the organization of the thalamic reticular nucleus. In crocodiles, at least, the neurons in the thalamic reticular nucleus are heterogeneous with two separate nuclei each being associated with a different circuit. In mammals, the neurons in the thalamic reticular nucleus, which is a single structure, are homogeneous. Transcriptomics and development are suggested to be the most likely approaches to explain these differences between reptiles and mammals. Transcriptomics can reveal which neuron types are 'new' or 'old' and whether neurons and their respective circuits have been re-purposed to be used differently. Examination of the development and connections of the dorsal and ventral thalamus will determine whether their formation is similar or different from what has been described for mammals.

Transcriptomic diversity of amygdalar subdivisions across humans and nonhuman primates.

The amygdaloid complex mediates learning, memory, and emotions. Understanding the cellular and anatomical features that are specialized in the amygdala of primates versus other vertebrates requires a systematic, anatomically-resolved molecular analysis of constituent cell populations. We analyzed five nuclear subdivisions of the primate amygdala with single-nucleus RNA sequencing in macaques, baboons, and humans to examine gene expression profiles for excitatory and inhibitory neurons and confirmed our results with single-molecule FISH analysis. We identified distinct subtypes of FOXP2 + interneurons in the intercalated cell masses and protein-kinase C-δ interneurons in the central nucleus. We also establish that glutamatergic, pyramidal-like neurons are transcriptionally specialized within the basal, lateral, or accessory basal nuclei. Understanding the molecular heterogeneity of anatomically-resolved amygdalar neuron types provides a cellular framework for improving existing models of how amygdalar neural circuits contribute to cognition and mental health in humans by using nonhuman primates as a translational bridge.

Compressed sensing based approach identifies modular neural circuitry driving learned pathogen avoidance.

An animal's survival hinges on its ability to integrate past information to modify future behavior. The nematode C. elegans adapts its behavior based on prior experiences with pathogen exposure, transitioning from attraction to avoidance of the pathogen. A systematic screen for the neural circuits that integrate the information of previous pathogen exposure to modify behavior has not been feasible because of the lack of tools for neuron type specific perturbations. We overcame this challenge using methods based on compressed sensing to efficiently determine the roles of individual neuron types in learned avoidance behavior. Our screen revealed that distinct sets of neurons drive exit from lawns of pathogenic bacteria and prevent lawn re-entry. Using calcium imaging of freely behaving animals and optogenetic perturbations, we determined the neural dynamics that regulate one key behavioral transition after infection: stalled re-entry into bacterial lawns. We find that key neuron types govern pathogen lawn specific stalling but allow the animal to enter nonpathogenic E. coli lawns. Our study shows that learned pathogen avoidance requires coordinated transitions in discrete neural circuits and reveals the modular structure of this complex adaptive behavioral response to infection.

A Model-Driven Meta-Analysis Supports the Emerging Consensus View that Inhibitory Neurons Dominate BOLD-fMRI Responses.

Functional magnetic resonance imaging (fMRI) is a pivotal tool for mapping neuronal activity in the brain. Traditionally, the observed hemodynamic changes are assumed to reflect the activity of the most common neuronal type: excitatory neurons. In contrast, recent experiments, using optogenetic techniques, suggest that the fMRI-signal instead reflects the activity of inhibitory interneurons. However, these data paint a complex picture, with numerous regulatory interactions, and where the different experiments display many qualitative differences. It is therefore not trivial how to quantify the relative contributions of the different cell types and to combine all observations into a unified theory. To address this, we present a new model-driven meta-analysis, which provides a unified and quantitative explanation for all data. This model-driven analysis allows for quantification of the relative contribution of different cell types: the contribution to the BOLD-signal from the excitatory cells is <20 % and 50-80 % comes from the interneurons. Our analysis also provides a mechanistic explanation for the observed experiment-to-experiment differences, e.g. a biphasic vascular response dependent on different stimulation intensities and an emerging secondary post-stimulation peak during longer stimulations. In summary, our study provides a new, emerging consensus-view supporting the larger role of interneurons in fMRI.

Heterozygous expression of a Kcnt1 gain-of-function variant has differential effects on somatostatin- and parvalbumin-expressing cortical GABAergic neurons

More than 20 recurrent missense gain-of-function (GOF) mutations have been identified in the sodium-activated potassium (KNa) channel gene KCNT1 in patients with severe developmental and epileptic encephalopathies (DEEs), most of which are resistant to current therapies. Defining the neuron types most vulnerable to KCNT1 GOF will advance our understanding of disease mechanisms and provide refined targets for precision therapy efforts. Here, we assessed the effects of heterozygous expression of a Kcnt1 GOF variant (Kcnt1Y777H) on KNa currents and neuronal physiology among cortical glutamatergic and GABAergic neurons in mice, including those expressing vasoactive intestinal polypeptide (VIP), somatostatin (SST), and parvalbumin (PV), to identify and model the pathogenic mechanisms of autosomal dominant KCNT1 GOF variants in DEEs. Although the Kcnt1Y777H variant had no effects on glutamatergic or VIP neuron function, it increased subthreshold KNa currents in both SST and PV neurons but with opposite effects on neuronal output; SST neurons became hypoexcitable with a higher rheobase current and lower action potential (AP) firing frequency, whereas PV neurons became hyperexcitable with a lower rheobase current and higher AP firing frequency. Further neurophysiological and computational modeling experiments showed that the differential effects of the Kcnt1Y777H variant on SST and PV neurons are not likely due to inherent differences in these neuron types, but to an increased persistent sodium current in PV, but not SST, neurons. The Kcnt1Y777H variant also increased excitatory input onto, and chemical and electrical synaptic connectivity between, SST neurons. Together, these data suggest differential pathogenic mechanisms, both direct and compensatory, contribute to disease phenotypes, and provide a salient example of how a pathogenic ion channel variant can cause opposite functional effects in closely related neuron subtypes due to interactions with other ionic conductances.

Heterozygous expression of a Kcnt1 gain-of-function variant has differential effects on somatostatin- and parvalbumin-expressing cortical GABAergic neurons.

More than 20 recurrent missense gain-of-function (GOF) mutations have been identified in the sodium-activated potassium (KNa) channel gene KCNT1 in patients with severe developmental and epileptic encephalopathies (DEEs), most of which are resistant to current therapies. Defining the neuron types most vulnerable to KCNT1 GOF will advance our understanding of disease mechanisms and provide refined targets for precision therapy efforts. Here, we assessed the effects of heterozygous expression of a Kcnt1 GOF variant (Kcnt1Y777H) on KNa currents and neuronal physiology among cortical glutamatergic and GABAergic neurons in mice, including those expressing vasoactive intestinal polypeptide (VIP), somatostatin (SST), and parvalbumin (PV), to identify and model the pathogenic mechanisms of autosomal dominant KCNT1 GOF variants in DEEs. Although the Kcnt1Y777H variant had no effects on glutamatergic or VIP neuron function, it increased subthreshold KNa currents in both SST and PV neurons but with opposite effects on neuronal output; SST neurons became hypoexcitable with a higher rheobase current and lower action potential (AP) firing frequency, whereas PV neurons became hyperexcitable with a lower rheobase current and higher AP firing frequency. Further neurophysiological and computational modeling experiments showed that the differential effects of the Kcnt1Y777H variant on SST and PV neurons are not likely due to inherent differences in these neuron types, but to an increased persistent sodium current in PV, but not SST, neurons. The Kcnt1Y777H variant also increased excitatory input onto, and chemical and electrical synaptic connectivity between, SST neurons. Together, these data suggest differential pathogenic mechanisms, both direct and compensatory, contribute to disease phenotypes, and provide a salient example of how a pathogenic ion channel variant can cause opposite functional effects in closely related neuron subtypes due to interactions with other ionic conductances.

Deciphering Peripheral Taste Neuron Diversity: Using Genetic Identity to Bridge Taste Bud Innervation Patterns and Functional Responses.

Peripheral taste neurons exhibit functional, genetic, and morphological diversity, yet understanding how or if these attributes combine into taste neuron types remains unclear. In this study, we used male and female mice to relate taste bud innervation patterns to the function of a subset of proenkephalin-expressing (Penk+) taste neurons. We found that taste arbors (the portion of the axon within the taste bud) stemming from Penk+ neurons displayed diverse branching patterns and lacked stereotypical endings. The range in complexity observed for individual taste arbors from Penk+ neurons mirrored the entire population, suggesting that taste arbor morphologies are not primarily regulated by neuron type. Notably, the distinguishing feature of arbors from Penk+ neurons was their propensity to come within 110 nm (in apposition with) different types of taste-transducing cells within the taste bud. This finding is contrary to the expectation of genetically defined taste neuron types that functionally represent a single stimulus. Consistently, further investigation of Penk+ neuron function revealed that they are more likely to respond to innately aversive stimuli -sour, bitter and high salt concentrations - as compared to the full taste population. Penk+ neurons are less likely to respond to non-aversive stimuli -sucrose, umami, and low salt- compared to the full population. Our data support the presence of a genetically defined neuron type in the geniculate ganglion that is responsive to innately aversive stimuli. This implies that genetic expression might categorize peripheral taste neurons into hedonic groups, rather than simply identifying neurons that respond to a single stimulus.Significance Statement Peripheral taste neuron coding has been heavily debated. Our study delves into this issue by leveraging genetic expression in a specific neuron subset to relate peripheral innervation patterns to functional taste responses. We examined a taste neuron type that appears to be in apposition with multiple taste-transducing cell types and responds to innately aversive concentrations of sour, bitter, and high NaCl stimuli. These collective observations suggest that genetic markers can delineate groups of neurons sharing similar hedonic responses rather than categorizing neurons solely based on individual taste qualities.

Molecular states underlying neuronal cell type development and plasticity in the whisker cortex.

A single-nucleus transcriptomic atlas of the whisker somatosensory cortex (wS1) during early postnatal developmentDifferent neuronal subclasses in wS1 show distinct developmental gene expression changesThe composition of L2/3 glutamatergic neurons changes between the second and the third postnatal weekDevelopmental gene expression and cell type changes are conserved between wS1 and the primary visual cortex (V1)Unlike V1, these changes are not affected by prolonged sensory deprivationBrief whisker deprivation induces subclass-specific activity-dependent gene expression in a whisker column-specific fashion.

Molecular logic for cellular specializations that initiate the auditory parallel processing pathways.

The cochlear nuclear complex (CN), the starting point for all central auditory processing, comprises a suite of neuronal cell types that are highly specialized for neural coding of acoustic signals, yet molecular logic governing cellular specializations remains unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple new subtypes with anatomical and physiological identity. The resulting comprehensive cell-type taxonomy reconciles anatomical position, morphological, physiological, and molecular criteria, enabling the determination of the molecular basis of the remarkable cellular phenotypes in the CN. In particular, CN cell-type identity is encoded in a transcriptional architecture that orchestrates functionally congruent expression across a small set of gene families to customize projection patterns, input-output synaptic communication, and biophysical features required for encoding distinct aspects of acoustic signals. This high-resolution account of cellular heterogeneity from the molecular to the circuit level illustrates molecular logic for cellular specializations and enables genetic dissection of auditory processing and hearing disorders with unprecedented specificity.

Selective vulnerability of parvocellular oxytocin neurons in social dysfunction

Selective vulnerability offers a conceptual framework for understanding neurodegenerative disorders such as Parkinson’s disease, where specific neuronal types are selectively affected and adjacent ones are spared. However, the applicability of this framework to neurodevelopmental disorders, particularly those characterized by atypical social behaviors, such as autism spectrum disorder, remains uncertain. Here we show that an embryonic disturbance, known to induce social dysfunction in male mice, preferentially impaired the gene expression crucial for neural functions in parvocellular oxytocin (OT) neurons—a subtype linked to social rewards—while neighboring cell types experienced a lesser impact. Chemogenetic stimulation of OT neurons at the neonatal stage ameliorated social deficits in early adulthood, concurrent with cell-type-specific sustained recovery of pivotal gene expression within parvocellular OT neurons. Collectively, our data shed light on the transcriptomic selective vulnerability within the hypothalamic social behavioral center and provide a potential therapeutic target through specific neonatal neurostimulation.

Enhanced neural activity detection with microelectrode arrays modified by drug-loaded calcium alginate/chitosan hydrogel

Microelectrode arrays (MEAs) are pivotal brain-machine interface devices that facilitate in situ and real-time detection of neurophysiological signals and neurotransmitter data within the brain. These capabilities are essential for understanding neural system functions, treating brain disorders, and developing advanced brain-machine interfaces. To enhance the performance of MEAs, this study developed a crosslinked hydrogel coating of calcium alginate (CA) and chitosan (CS) loaded with the anti-inflammatory drug dexamethasone sodium phosphate (DSP). By modifying the MEAs with this hydrogel and various conductive nanomaterials, including platinum nanoparticles (PtNPs) and poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS), the electrical properties and biocompatibility of the electrodes were optimized. The hydrogel coating matches the mechanical properties of brain tissue more effectively and, by actively releasing anti-inflammatory drugs, significantly reduces post-implantation tissue inflammation, extends the electrodes' lifespan, and enhances the quality of neural activity detection. Additionally, this modification ensures high sensitivity and specificity in the detection of dopamine (DA), displaying high-quality dual-mode neural activity during in vivo testing and revealing significant functional differences between neuron types under various physiological states (anesthetized and awake). Overall, this study showcases the significant application value of bioactive hydrogels as excellent nanobiointerfaces and drug delivery carriers for long-term neural monitoring. This approach has the potential to enhance the functionality and acceptance of brain-machine interface devices in medical practice and has profound implications for future neuroscience research and the development of strategies for treating neurological diseases.

Longitudinal autophagy profiling of the mammalian brain reveals sustained mitophagy throughout healthy aging.

Mitophagy neutralizes mitochondrial damage, thereby preventing cellular dysfunction and apoptosis. Defects in mitophagy have been strongly implicated in age-relatedneurodegenerative disorders such as Parkinson's and Alzheimer's disease. While mitophagy decreases throughout the lifespan of short-lived model organisms, it remains unknown whether such a decline occurs in the aging mammalian brain-a question of fundamental importance for understanding cell type- and region-specific susceptibility to neurodegeneration. Here, we define the longitudinal dynamics of basal mitophagy and macroautophagy across neuronal and non-neuronal cell types within the intact aging mouse brain in vivo. Quantitative profiling of reporter mouse cohorts from young to geriatric ages reveals cell- and tissue-specific alterations in mitophagy and macroautophagy between distinct subregions and cell populations, including dopaminergic neurons, cerebellar Purkinje cells, astrocytes, microglia and interneurons. We also find that healthy aging is hallmarked by the dynamic accumulation of differentially acidified lysosomes in several neural cell subsets. Our findings argue against any widespread age-related decline in mitophagic activity, instead demonstrating dynamic fluctuations in mitophagy across the aging trajectory, withstrong implications for ongoing theragnostic development.

Excitation-inhibition imbalance in medial preoptic area circuits underlies chronic stress-induced depression-like states

Dysregulation of brain homeostasis is associated with neuropsychiatric conditions such as major depressive disorder. However, underlying neural-circuit mechanisms remain not well-understood. We show in mice that chronic restraint stress (CRS) and social defeat stress (SDS) are both associated with disruption of excitation (E)-inhibition (I) balance, with increased E/I ratios, in medial preoptic area (MPOA) circuits, but through affecting different neuronal types. CRS results in elevated activity in glutamatergic neurons, and their suppression mitigates CRS-induced depressive-like behaviors. Paraventricular hypothalamic input to these neurons contributes to induction but not expression of depressive-like behaviors. Their projections to ventral tegmental area and periaqueductal gray/dorsal raphe suppress midbrain dopaminergic and serotonergic activity, respectively, and mediate expression of divergent depressive-like symptoms. By contrast, SDS results in reduced activity of GABAergic neurons, and their activation alleviates SDS-induced depressive-like behaviors. Thus, E/I imbalance with relatively increased excitation in MPOA circuits may be a general mechanism underlying depression caused by different etiological factors.

Protein kinase R induced by type I interferons is a main regulator of reactive microglia in Zika virus infection.

Microglial cells are the phagocytic cells of the brain that under physiological conditions participate in brain homeostasis and surveillance. Under pathogenic states, microglia undergoes strong morphological and transcriptional changes potentially leading to sustained neuroinflammation, brain damage, and cognitive disorders. Postnatal and adult Zika virus (ZIKV) brain infection is characterized by the induction of reactive microglia associated with brain inflammation, synapse loss and neuropathogenesis. Contrary to neurons, microglial cells are not infected by ZIKV thus raising the question of the mechanism governing ZIKV-induced microglia's reactivity. In this work, we have questioned the role of exogenous, neuronal type I interferons (IFNs-I) in regulating ZIKV-induced microglia's reactivity. Primary cultured microglial cells were either treated with conditioned media from ZIKV-infected mature neurons or co-cultured with ZIKV-infected neurons. Using either an antibody directed against the IFNAR receptor that neutralizes the IFNs-I response or Ifnar-/-microglial cells, we demonstrate that IFNs-I produced by ZIKV-infected neurons are the main regulators of the phagocytic capacity and the pro-inflammatory gene expression profile of reactive, non-infected microglial cells. We identify protein kinase R (PKR), whose expression is activated by IFNs-I, as a major regulator of the phagocytic capacity, pro-inflammatory response, and morphological changes of microglia induced by IFNs-I while up-regulating STAT1 phosphorylation and IRF1 expression. Results obtained herein in vitro with primary cultured cells and in vivo in ZIKV-infected adult immunocompetent mice, unravel a role for IFNs-I and PKR in directly regulating microglia's reactivity that could be at work in other infectious and non-infectious brain pathologies.

Connectomic reconstruction predicts visual features used for navigation

Many animals use visual information to navigate1–4, 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 direction5 by integrating visual input from ER neurons6–12, which are part of the anterior visual pathway (AVP)10,13–16. Here we densely reconstruct all neurons in the AVP using electron-microscopy data17. The AVP comprises four neuropils, sequentially linked by three major classes of neurons: MeTu neurons10,14,15, which connect the medulla in the optic lobe to the small unit of the anterior optic tubercle (AOTUsu) in the central brain; TuBu neurons9,16, which connect the AOTUsu to the bulb neuropil; and ER neurons6–12, 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.

Neuronal parts list and wiring diagram for a visual system

A catalogue of neuronal cell types has often been called a ‘parts list’ of the brain1, and regarded as a prerequisite for understanding brain function2,3. In the optic lobe of Drosophila, rules of connectivity between cell types have already proven to be essential for understanding fly vision4,5. Here we analyse the fly connectome to complete the list of cell types intrinsic to the optic lobe, as well as the rules governing their connectivity. Most new cell types contain 10 to 100 cells, and integrate information over medium distances in the visual field. Some existing type families (Tm, Li, and LPi)6–10 at least double in number of types. A new serpentine medulla (Sm) interneuron family contains more types than any other. Three families of cross-neuropil types are revealed. The consistency of types is demonstrated by analysing the distances in high-dimensional feature space, and is further validated by algorithms that select small subsets of discriminative features. We use connectivity to hypothesize about the functional roles of cell types in motion, object and colour vision. Connectivity with ‘boundary types’ that straddle the optic lobe and central brain is also quantified. We showcase the advantages of connectomic cell typing: complete and unbiased sampling, a rich array of features based on connectivity and reduction of the connectome to a substantially simpler wiring diagram of cell types, with immediate relevance for brain function and development.