Sensory Circuits Research Articles

Organization of the gravity-sensing system in zebrafish

Motor circuits develop in sequence from those governing fast movements to those governing slow. Here we examine whether upstream sensory circuits are organized by similar principles. Using serial-section electron microscopy in larval zebrafish, we generated a complete map of the gravity-sensing (utricular) system spanning from the inner ear to the brainstem. We find that both sensory tuning and developmental sequence are organizing principles of vestibular topography. Patterned rostrocaudal innervation from hair cells to afferents creates an anatomically inferred directional tuning map in the utricular ganglion, forming segregated pathways for rostral and caudal tilt. Furthermore, the mediolateral axis of the ganglion is linked to both developmental sequence and neuronal temporal dynamics. Early-born pathways carrying phasic information preferentially excite fast escape circuits, whereas later-born pathways carrying tonic signals excite slower postural and oculomotor circuits. These results demonstrate that vestibular circuits are organized by tuning direction and dynamics, aligning them with downstream motor circuits and behaviors.

Distributed interfacing by nanoscale photodiodes enables single-neuron light activation and sensory enhancement in 3D spinal explants.

Among emerging technologies developed to interface neuronal signaling, engineering electrodes at the nanoscale would yield more precise biodevices opening to progress in neural circuit investigations and to new therapeutic potential. Despite remarkable progress in miniature electronics for less invasive neurostimulation, most nano-enabled, optically triggered interfaces are demonstrated in cultured cells, which precludes the studies of natural neural circuits. We exploit here free-standing silicon-based nanoscale photodiodes to optically modulate single, identified neurons in mammalian spinal cord explants. With near-infrared light stimulation, we show that activating single excitatory or inhibitory neurons differently affects sensory circuits processing in the dorsal horn. We successfully functionalize nano-photodiodes to target single molecules, such as glutamate AMPA receptor subunits, thus enabling light activation of specific synaptic pathways. We conclude that nano-enabled neural interfaces can modulate selected sensory networks with low invasiveness. The use of nanoscale photodiodes can thus provide original perspective in linking neural activity to specific behavioral outcome.

Synapse-specific roles for microglia in development: New horizons in the prefrontal cortex.

Dysfunction of both microglia and circuitry in the medial prefrontal cortex (mPFC) have been implicated in numerous neuropsychiatric disorders, but how microglia affect mPFC development in health and disease is not well understood. mPFC circuits undergo a prolonged maturation after birth that is driven by molecular programs and activity-dependent processes. Though this extended development is crucial to acquire mature cognitive abilities, it likely renders mPFC circuitry more susceptible to disruption by genetic and environmental insults that increase the risk of developing mental health disorders. Recent work suggests that microglia directly influence mPFC circuit maturation, though the biological factors underlying this observation remain unclear. In this review, we discuss these recent findings along with new studies on the cellular mechanisms by which microglia shape sensory circuits during postnatal development. We focus on the molecular pathways through which glial cells and immune signals regulate synaptogenesis and activity-dependent synaptic refinement. We further highlight how disruptions in these pathways are implicated in the pathogenesis of neurodevelopmental and psychiatric disorders associated with mPFC dysfunction, including schizophrenia and autism spectrum disorder (ASD). Using these disorders as a framework, we discuss microglial mechanisms that could link environmental risk factors including infections and stress with ongoing genetic programs to aberrantly shape mPFC circuitry.

Blind cavefish retain functional connectivity in the tectum despite loss of retinal input

Sensory systems display remarkable plasticity and are under strong evolutionary selection. The Mexican cavefish, Astyanax mexicanus, consists of eyed river-dwelling surface populations and multiple independent cave populations that have converged on eye loss, providing the opportunity to examine the evolution of sensory circuits in response to environmental perturbation. Functional analysis across multiple transgenic populations expressing GCaMP6s showed that functional connectivity of the optic tectum largely did not differ between populations, except for the selective loss of negatively correlated activity within the cavefish tectum, suggesting positively correlated neural activity is resistant to an evolved loss of input from the retina. Furthermore, analysis of surface-cave hybrid fish reveals that changes in the tectum are genetically distinct from those encoding eye loss. Together, these findings uncover the independent evolution of multiple components of the visual system and establish the use of functional imaging in A.mexicanus to study neural circuit evolution.

Magnitudes for Nervous Systems: Theoretical Issues and Experimental Evidence

Animals’ negotiations with the environment frequently involve quantitative assessments. However, it is largely unknown how different nervous systems can deal with information about magnitude and perform operations on it. Here we review some of the literature on this topic and discuss a few issues worthy of debate that can guide future research directions. First, we present experimental evidence suggesting that, in addition to the cortical (pallial) brain regions that are widely acknowledged to play a role in magnitude estimation, subcortical (more generally, subpallial) brain regions also play an important role. Second, we discuss interactions between different domains of magnitude and put forward a hypothesis to account for the directionality of associations between discrete and continuous magnitude. Finally, we suggest how the distinction between the concepts of number and discrete quantity should foster more attention to the role of sensory areas and circuits in assessing discrete quantities.

A Programmable Ontology Encompassing the Functional Logic of the Drosophila Brain.

The Drosophila brain has only a fraction of the number of neurons of higher organisms such as mice and humans. Yet the sheer complexity of its neural circuits recently revealed by large connectomics datasets suggests that computationally modeling the function of fruit fly brain circuits at this scale poses significant challenges. To address these challenges, we present here a programmable ontology that expands the scope of the current Drosophila brain anatomy ontologies to encompass the functional logic of the fly brain. The programmable ontology provides a language not only for modeling circuit motifs but also for programmatically exploring their functional logic. To achieve this goal, we tightly integrated the programmable ontology with the workflow of the interactive FlyBrainLab computing platform. As part of the programmable ontology, we developed NeuroNLP++, a web application that supports free-form English queries for constructing functional brain circuits fully anchored on the available connectome/synaptome datasets, and the published worldwide literature. In addition, we present a methodology for including a model of the space of odorants into the programmable ontology, and for modeling olfactory sensory circuits of the antenna of the fruit fly brain that detect odorant sources. Furthermore, we describe a methodology for modeling the functional logic of the antennal lobe circuit consisting of a massive number of local feedback loops, a characteristic feature observed across Drosophila brain regions. Finally, using a circuit library, we demonstrate the power of our methodology for interactively exploring the functional logic of the massive number of feedback loops in the antennal lobe.

Using newly optimized genetic tools to probe Strongyloides sensory behaviors

The oft-neglected human-parasitic threadworm, Strongyloides stercoralis, infects roughly eight percent of the global population, placing disproportionate medical and economic burden upon marginalized communities. While current chemotherapies treat strongyloidiasis, disease recrudescence and the looming threat of anthelminthic resistance necessitate novel strategies for nematode control. Throughout its life cycle, S. stercoralis relies upon sensory cues to aid in environmental navigation and coordinate developmental progression. Odorants, tastants, gases, and temperature have been shown to shape parasite behaviors that drive host seeking and infectivity; however, many of these sensory behaviors remain poorly understood, and their underlying molecular and neural mechanisms are largely uncharacterized. Disruption of sensory circuits essential to parasitism presents a promising strategy for future interventions. In this review, we describe our current understanding of sensory behaviors – namely olfactory, gustatory, gas sensing, and thermosensory behaviors – in Strongyloides spp. We also highlight the ever-growing cache of genetic tools optimized for use in Strongyloides that have facilitated these findings, including transgenesis, CRISPR/Cas9-mediated mutagenesis, RNAi, chemogenetic neuronal silencing, and the use of fluorescent biosensors to measure neuronal activity. Bolstered by these tools, we are poised to enter an era of rapid discovery in Strongyloides sensory neurobiology, which has the potential to shape pioneering advances in the prevention and treatment of strongyloidiasis.

A cross-taxonomic perspective on the integration of temperature cues in vertebrate seasonal neuroendocrine pathways

The regulation of seasonality has been an area of interest for decades, yet global climate change has created extra urgency in the quest to understand how sensory circuits and neuroendocrine control systems interact to generate flexibility in biological timekeeping. The capacity of temperature to alter endogenous or photoperiod-regulated neuroendocrine mechanisms driving seasonality, either as a direct cue or through temperature-dependent effects on energy and metabolism, is at the heart of this phenological flexibility. However, until relatively recently, little research had been done on the integration of temperature information in canonical seasonal neuroendocrine pathways, particularly in vertebrates. We review recent advances from research in vertebrates that deepens our understanding of how temperature cues are perceived and integrated into seasonal hypothalamic thyroid hormone (TH) signaling, which is a critical regulator of downstream seasonal phenotypic changes such as those regulated by the BPG (brain-pituitary-gonadal) axis. Temperature perception occurs through cutaneous transient receptor potential (TRP) neurons, though sensitivity of these neurons varies markedly across taxa. Although photoperiod is the dominant cue used to trigger seasonal physiology or entrain circannual clocks, across birds, mammals, fish, reptiles and amphibians, seasonality appears to be temperature sensitive and in at least some cases this appears to be related to phylogenetically conserved TH signaling in the hypothalamus. Nevertheless, the exact mechanisms through which temperature modulates seasonal neuroendocrine pathways remains poorly understood.

Recruitment of frontal sensory circuits during visual discrimination.

SummaryA long-range circuit linking the medial frontal cortex to the primary visual cortex (V1) has been proposed to mediate visual selective attention in mice during visually guided behavior. Here, we use in vivo two-photon functional imaging to measure the endogenous activity of axons of A24b/M2 neurons from this region projecting to layer 1 of V1 (A24b/M2-V1axons) in mice either passively viewing stimuli or performing a go/no-go visually guided task. We observe that while A24b/M2-V1axons are recruited under these conditions, this is not linked to enhancement of neural or behavioral measures of sensory coding. Instead, A24b/M2-V1axon activity is associated with licking behavior, modulated by reward, and biased toward the sensory cortical hemisphere representing the stimulus currently being discriminated.

Epigenetic and Transcriptional Regulation of Spontaneous and Sensory Activity Dependent Programs During Neuronal Circuit Development.

Spontaneous activity generated before the onset of sensory transduction has a key role in wiring developing sensory circuits. From axonal targeting, to synapse formation and elimination, to the balanced integration of neurons into developing circuits, this type of activity is implicated in a variety of cellular processes. However, little is known about its molecular mechanisms of action, especially at the level of genome regulation. Conversely, sensory experience-dependent activity implements well-characterized transcriptional and epigenetic chromatin programs that underlie heterogeneous but specific genomic responses that shape both postnatal circuit development and neuroplasticity in the adult. In this review, we focus on our knowledge of the developmental processes regulated by spontaneous activity and the underlying transcriptional mechanisms. We also review novel findings on how chromatin regulates the specificity and developmental induction of the experience-dependent program, and speculate their relevance for our understanding of how spontaneous activity may act at the genomic level to instruct circuit assembly and prepare developing neurons for sensory-dependent connectivity refinement and processing.

Diurnal changes in the efficiency of information transmission at a sensory synapse

Neuromodulators adapt sensory circuits to changes in the external world or the animal’s internal state and synapses are key control sites for such plasticity. Less clear is how neuromodulation alters the amount of information transmitted through the circuit. We investigated this question in the context of the diurnal regulation of visual processing in the retina of zebrafish, focusing on ribbon synapses of bipolar cells. We demonstrate that contrast-sensitivity peaks in the afternoon accompanied by a four-fold increase in the average Shannon information transmitted from an active zone. This increase reflects higher synaptic gain, lower spontaneous “noise” and reduced variability of evoked responses. Simultaneously, an increase in the probability of multivesicular events with larger information content increases the efficiency of transmission (bits per vesicle) by factors of 1.5-2.7. This study demonstrates the multiplicity of mechanisms by which a neuromodulator can adjust the synaptic transfer of sensory information.

Olfactory sensory experience regulates gliomagenesis via neuronal IGF1.

Animals constantly receive various sensory stimuli, such as odours, sounds, light and touch, from the surrounding environment. These sensory inputs are essential for animals to search for food and avoid predators, but they also affect their physiological status, and may cause diseases such as cancer. Malignant gliomas-the most lethal form of brain tumour1-are known to intimately communicate with neurons at the cellular level2,3. However, it remains unclear whether external sensory stimuli can directly affect the development of malignant glioma under normal living conditions. Here we show that olfaction can directly regulate gliomagenesis. In an autochthonous mouse model that recapitulates adult gliomagenesis4-6 originating in oligodendrocyte precursor cells (OPCs), gliomas preferentially emerge in the olfactory bulb-the first relay of brain olfactory circuitry. Manipulating the activity of olfactory receptor neurons (ORNs) affects the development of glioma. Mechanistically, olfaction excites mitral and tufted (M/T) cells, which receive sensory information from ORNs and release insulin-like growth factor1 (IGF1) in an activity-dependent manner. Specific knockout of Igf1 in M/T cells suppresses gliomagenesis. In addition, knocking out the IGF1 receptor in pre-cancerous mutant OPCs abolishes the ORN-activity-dependent mitogenic effects. Our findings establish a link between sensory experience and gliomagenesis through their corresponding sensory neuronal circuits.

Large-conductance calcium-activated potassium channel haploinsufficiency leads to sensory deficits in the visual system: a case report

BackgroundMutations in the genes encoding the large-conductance calcium-activated potassium channel, especially KCNMA1 encoding its α-subunit, have been linked to several neurological features, including intellectual disability or autism. Associated with neurodevelopmental phenotypes, sensory function disturbances are considered to be important clinical features contributing to a variety of behavioral impairments. Large-conductance calcium-activated potassium channels are important in regulating neurotransmission in sensory circuits, including visual pathways. Deficits in visual function can contribute substantially to poor quality of life, while therapeutic approaches aimed at addressing such visual deficits represent opportunities to improve neurocognitive and neurobehavioral outcomes.Case presentationWe describe the case of a 25-year-old Caucasian male with autism spectrum disorder and severe intellectual disability presenting large-conductance calcium-activated potassium channel haploinsufficiency due to a de novo balanced translocation (46, XY, t [9; 10] [q23;q22]) disrupting the KCNMA1 gene. The visual processing pathway of the subject was evaluated using both electroretinography and visual contrast sensitivity, indicating that both retinal bipolar cell function and contrast discrimination performance were reduced by approximately 60% compared with normative control values. These findings imply a direct link between KCNMA1 gene disruption and visual dysfunction in humans. In addition, the subject reported photophobia but did not exhibit strabismus, nystagmus, or other visual findings on physical examination.ConclusionsThis case study of a subject with large-conductance calcium-activated potassium channel haploinsufficiency and photophobia revealed a visual pathway deficit at least at the retinal level, with diminished retinal light capture likely due to bipolar cell dysfunction and an associated loss of contrast sensitivity. The data suggest that large-conductance calcium-activated potassium channels play an important role in the normal functioning of the visual pathway in humans, and that their disruption may play a role in visual and other sensory system symptomatology in large-conductance calcium-activated potassium channelopathies or conditions where disruption of large-conductance calcium-activated potassium channel function is a relevant feature of the pathophysiology, such as fragile X syndrome. This work suggests that the combined use of physiological (electroretinography) and functional (contrast sensitivity) approaches may have utility as a biomarker strategy for identifying and characterizing visual processing deficits in individuals with large-conductance calcium-activated potassium channelopathy.Trial registration ID-RCB number 2019-A01015-52, registered 17/05/2019.

Crosstalk between skin homing innate T cells and epithelial cells via cholesterol byproduct messengers is required for tissue immunity

Abstract Innate T cells and innate lymphoid cells in barrier tissues are essential for both tissue fitness and immunity against pathogens. γδTCR+ lymphocytes that secrete IL-17 (Tγδ17) localize to dermis and are critical regulators of skin immune responses. Despite their functional importance, how Tγδ17 cells mediate their unique function in the skin is largely unknown. Tγδ17 cells express the two prototypic G-protein coupled receptors (GPCRs) CCR6 and GPR183 (EBI2): mice lacking both receptors had significantly diminished dermal Tγδ17 cells and were resistant to psoriasis induction. This was due to a block in Tγδ17 cell maturation in the thymus of Ccr6−/−Gpr183−/− double knock-out mice. EBI2 recognizes oxysterols generated by the cholesterol hydroxylase CH25H and functional oxysterols were detected in both the thymus and skin. Analysis of Ch25h-reporter mice showed that interfollicular epithelial cells (IFEs) and a subset of medullary thymic epithelial cells (mTEC) are the depot for oxysterols in skin and thymus respectively. Ch25h+ TECs were also identified by unbiased single cell transcriptome analyses. These results demonstrate that developing Tγδ17 cells must be conditioned by sensing cholesterol byproducts synthesized by a discrete subset of mTECs to position in specific oxysterol rich niches in the skin. Moreover, in the skin, dietary cholesterol increased tissue oxysterol concentration and modulated homeostatic and pathogenic effector function of Tγδ17 cells in a EBI2 dependent fashion. Given that oxysterols can be regulated by infection and inflammation, this sensory circuit directed by cholesterol is predicted to program skin innate T cells’ ability to rapidly survey for perturbations in the skin. Supported by grant from NIH R21AI143225.

Alterations in somatosensory, visual and auditory pathways in amyotrophic lateral sclerosis: an under-recognised facet of ALS.

While amyotrophic lateral sclerosis (ALS) is widely recognised as a multi-network disorder with extensive frontotemporal and cerebellar involvement, sensory dysfunction is relatively under evaluated. Subtle sensory deficits have been sporadically reported, but there is a prevailing notion that sensory pathways may be relatively spared in ALS. In a prospective neuroimaging study we have systematically evaluated cerebral grey and white matter structures involved in the processing, relaying and mediation of sensory information. Twenty two C9orf72 positive ALS patients (C9+ ALS), 138 C9orf72 negative ALS patients (C9- ALS) and 127 healthy controls were included. Widespread cortical alterations were observed in C9+ ALS including both primary and secondary somatosensory regions. In C9- ALS, cortical thickness reductions were observed in the postcentral gyrus. Thalamic nuclei relaying somatosensory information as well as the medial and lateral geniculate nuclei exhibited volume reductions. Diffusivity indices revealed posterior thalamic radiation pathology and a trend of left medial lemniscus degeneration was also observed in C9- ALS (p = 0.054). Our radiology data confirm the degeneration of somatosensory, visual and auditory pathways in ALS, which is more marked in GGGGCC hexanucleotide repeat expansion carriers. In contrast to the overwhelming focus on motor system degeneration and frontotemporal dysfunction in recent research studies, our findings confirm that sensory circuits are also affected in ALS. The involvement of somatosensory, auditory and visual pathways in ALS may have important clinical ramifications which are easily overlooked in the context of unremitting motor decline. Subtle sensory deficits may exacerbate mobility, contribute to fall risk, impair dexterity, and worsen bulbar dysfunction, therefore comprehensive sensory testing should also be performed as part of the clinical assessments in ALS.

What and Where: Location-Dependent Feature Sensitivity as a Canonical Organizing Principle of the Visual System.

Traditionally, functional representations in early visual areas are conceived as retinotopic maps preserving ego-centric spatial location information while ensuring that other stimulus features are uniformly represented for all locations in space. Recent results challenge this framework of relatively independent encoding of location and features in the early visual system, emphasizing location-dependent feature sensitivities that reflect specialization of cortical circuits for different locations in visual space. Here we review the evidence for such location-specific encoding including: (1) systematic variation of functional properties within conventional retinotopic maps in the cortex; (2) novel periodic retinotopic transforms that dramatically illustrate the tight linkage of feature sensitivity, spatial location, and cortical circuitry; and (3) retinotopic biases in cortical areas, and groups of areas, that have been defined by their functional specializations. We propose that location-dependent feature sensitivity is a fundamental organizing principle of the visual system that achieves efficient representation of positional regularities in visual experience, and reflects the evolutionary selection of sensory and motor circuits to optimally represent behaviorally relevant information. Future studies are necessary to discover mechanisms underlying joint encoding of location and functional information, how this relates to behavior, emerges during development, and varies across species.

P 30 Stereotactic Deep Brain Modulation Targeting the Somatosensory and Affective Pain Circuits of the Thalamus

Introduction: Despite tremendous advances in drug and physical therapy, chronic pain treatment remains challenging in a considerable proportion of individuals. It is not uncommon, especially in pain syndromes in a chronic state, for up to 20% of patients to be insufficiently analgesic leading to enormous economical as well as psychosocial consequences for affected individuals. When conventional therapies fail, modulation of the lateral and medial thalamic pain networks using reversible deep brain stimulation (DBS) or targeted irreversible thalamotomy by Gamma Knife Radiosurgery (GKRS), Radiofrequency ablation (RFA) or Magnetic Resonance (MR)-guided Focus Ultrasound (MRgFUS) appear to be considerable treatment options. Materials and Methods: We performed a literature search for clinical trials targeting the sensory and affective thalamic circuits relevant for pain processing. We performed searches on PubMed, Ovid MEDLINE, and Scopus. Furthermore, a manual library search was performed using the terms “chronic pain”, “thalamotomy”, “deep brain stimulation”, “ventral-postero-lateral nucleus of the thalamus”, “centrum-median parafascicular nucleus of the thalamus”, “affective thalamic pain transmission”, “somatosensory thalamic pain processing”, and “anterior cingulate cortex”. Results: We identified human studies on the modulation of the somatosensory and affective thalamic nuclei for four different stereotactic-guided procedures, namely DBS, GKRS, RFA, MRgFUS. Specifically, we identified a total number of 320 patients that has been treated with thalamaic DBS. Furthermore, DBS of the anterior cingulate cortex (ACC) revealed 5 human studies with a total of 54 implanted chronic pain patients. GKRS was performed in a total of 60 patients, while MRgFUS has been applied to a relatively low number of patients. Conclusions: While in contrast, the CmPf lacks such kind of topography indicating that both, VPL and CmPf, decrease pain levels by sensory and attentional modulation. DBS targeting the VPL evokes paraesthesia in the affected pain region of the body, while CmPf and ACC evokes similar DBS responses. Chronic pain stimulated in the CmPf or ACC reported unchanged pain levels, however, attention and emotional (affective distancing to chronic pain stimuli was observed in these cohorts of DBS patients (Fig. 1a). However, the available data is of heterogeneous and preliminary nature, hindering effective comparable analysis. Currently, there is no evidence in favour or against any stereotactic approach, hence, we advocate to establish recommendations and guidelines covering advantages and disadvantages of each approach, including such parameters as invasiveness, risk-benefit ratio, reversibility and responsiveness.

The Role of Inhibitory Interneurons in Circuit Assembly and Refinement Across Sensory Cortices

Sensory information is transduced into electrical signals in the periphery by specialized sensory organs, which relay this information to the thalamus and subsequently to cortical primary sensory areas. In the cortex, microcircuits constituted by interconnected pyramidal cells and inhibitory interneurons, distributed throughout the cortical column, form the basic processing units of sensory information underlying sensation. In the mouse, these circuits mature shortly after birth. In the first postnatal week cortical activity is characterized by highly synchronized spontaneous activity. While by the second postnatal week, spontaneous activity desynchronizes and sensory influx increases drastically upon eye opening, as well as with the onset of hearing and active whisking. This influx of sensory stimuli is fundamental for the maturation of functional properties and connectivity in neurons allocated to sensory cortices. In the subsequent developmental period, spanning the first five postnatal weeks, sensory circuits are malleable in response to sensory stimulation in the so-called critical periods. During these critical periods, which vary in timing and duration across sensory areas, perturbations in sensory experience can alter cortical connectivity, leading to long-lasting modifications in sensory processing. The recent advent of intersectional genetics, in vivo calcium imaging and single cell transcriptomics has aided the identification of circuit components in emergent networks. Multiple studies in recent years have sought a better understanding of how genetically-defined neuronal subtypes regulate circuit plasticity and maturation during development. In this review, we discuss the current literature focused on postnatal development and critical periods in the primary auditory (A1), visual (V1), and somatosensory (S1) cortices. We compare the developmental trajectory among the three sensory areas with a particular emphasis on interneuron function and the role of inhibitory circuits in cortical development and function.

Adaptive erasure of spurious sequences in sensory cortical circuits

Sequential activity reflecting previously experienced temporal sequences is considered a hallmark of learning across cortical areas. However, it is unknown how cortical circuits avoid the converse problem: producing spurious sequences that are not reflecting sequences in their inputs. We develop methods to quantify and study sequentiality in neural responses. We show that recurrent circuit responses generally include spurious sequences, which are specifically prevented in circuits that obey two widely known features of cortical microcircuit organization: Dale's law and Hebbian connectivity. In particular, spike-timing-dependent plasticity in excitation-inhibition networks leads to an adaptive erasure of spurious sequences. We tested our theory in multielectrode recordings from the visual cortex of awake ferrets. Although responses to natural stimuli were largely non-sequential, responses to artificial stimuli initially included spurious sequences, which diminished over extended exposure. These results reveal an unexpected role for Hebbian experience-dependent plasticity and Dale's law in sensory cortical circuits.

Emergence of Direction-Selective Retinal Cell Types in Task-Optimized Deep Learning Models.

Convolutional neural networks (CNNs), a class of deep learning models, have experienced recent success in modeling sensory cortices and retinal circuits through optimizing performance on machine learning tasks, otherwise known as task optimization. Previous research has shown task-optimized CNNs to be capable of providing explanations as to why the retina efficiently encodes natural stimuli and how certain retinal cell types are involved in efficient encoding. In our work, we sought to use task-optimized CNNs as a means of explaining computational mechanisms responsible for motion-selective retinal circuits. We designed a biologically constrained CNN and optimized its performance on a motion-classification task. We drew inspiration from psychophysics, deep learning, and systems neuroscience literature to develop a toolbox of methods to reverse engineer the computational mechanisms learned in our model. Through reverse engineering our model, we proposed a computational mechanism in which direction-selective ganglion cells and starburst amacrine cells, both experimentally observed retinal cell types, emerge in our model to discriminate among moving stimuli. This emergence suggests that direction-selective circuits in the retina are ecologically designed to robustly discriminate among moving stimuli. Our results and methods also provide a framework for how to build more interpretable deep learning models and how to understand them.