scholarly journals Neural correlates of individual odor preference in Drosophila

2021 ◽  
Author(s):  
Matthew Churgin ◽  
Danylo Lavrentovich ◽  
Matthew A-Y Smith ◽  
Ruixuan Gao ◽  
Edward S Boyden ◽  
...  
Keyword(s):  
Neural Coding ◽  
Neural Circuit ◽  
Projection Neurons ◽  
Structural Variations ◽  
Odor Preference ◽  
Stochastic Fluctuations ◽  
Ideal System ◽  
Individual Odor ◽  
Presynaptic Density ◽  
Odor Preferences

Behavior varies even among genetically identical animals raised in the same environment. However, little is known about the circuit or anatomical underpinnings of this individuality. Drosophila olfaction is an ideal system for discovering the origins of behavioral individuality among genetically identical individuals. The fly olfactory circuit is well-characterized and stereotyped, yet stable idiosyncrasies in odor preference, neural coding, and neural wiring are present and may be relevant to behavior. Using paired behavior and two-photon imaging measurements, we show that individual odor preferences in odor-vs-air and odor-vs-odor assays are predicted by idiosyncratic calcium dynamics in Olfactory Receptor Neurons (ORNs) and Projection Neurons (PNs), respectively. This suggests that circuit variation at the sensory periphery determines individual odor preferences. Furthermore, paired behavior and immunohistochemistry measurements reveal that variation in ORN presynaptic density also predicts odor-vs-odor preference. This point in the olfactory circuit appears to be a locus of individuality where microscale variation gives rise to idiosyncratic behavior. To unify these results, we constructed a leaky-integrate-and-fire model of 3,062 neurons in the antennal lobe. In these simulations, stochastic fluctuations at the glomerular level, like those observed in our ORN immunohistochemistry, produce variation in PN calcium responses with the same structure as we observed experimentally, the very structure that predicts idiosyncratic behavior. Thus, our results demonstrate how minute physiological and structural variations in a neural circuit may produce individual behavior, even when genetics and environment are held constant.

scholarly journals Activation of the dopaminergic pathway from VTA to the medial olfactory tubercle generates odor-preference and reward

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Zhijian Zhang ◽  
Qing Liu ◽  
Pengjie Wen ◽  
Jiaozhen Zhang ◽  
Xiaoping Rao ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Dopamine Receptors ◽  
Neural Circuit ◽  
Life Experiences ◽  
Olfactory Tubercle ◽  
Odor Preference ◽  
Dopaminergic Pathway ◽  
Different Types ◽  
Pharmacological Blockade ◽  
Odor Preferences

Odor-preferences are usually influenced by life experiences. However, the neural circuit mechanisms remain unclear. The medial olfactory tubercle (mOT) is involved in both reward and olfaction, whereas the ventral tegmental area (VTA) dopaminergic (DAergic) neurons are considered to be engaged in reward and motivation. Here, we found that the VTA (DAergic)-mOT pathway could be activated by different types of naturalistic rewards as well as odors in DAT-cre mice. Optogenetic activation of the VTA-mOT DAergic fibers was able to elicit preferences for space, location and neutral odor, while pharmacological blockade of the dopamine receptors in the mOT fully prevented the odor-preference formation. Furthermore, inactivation of the mOT-projecting VTA DAergic neurons eliminated the previously formed odor-preference and strongly affected the Go-no go learning efficiency. In summary, our results revealed that the VTA (DAergic)-mOT pathway mediates a variety of naturalistic reward processes and different types of preferences including odor-preference in mice.

scholarly journals A visual circuit uses complementary mechanisms to support transient and sustained pupil constriction

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
William Thomas Keenan ◽  
Alan C Rupp ◽  
Rachel A Ross ◽  
Preethi Somasundaram ◽  
Suja Hiriyanna ◽  
...  
Keyword(s):  
Neural Coding ◽  
Pupil Size ◽  
Neural Circuit ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Neural Basis ◽  
Behavioral Dynamics ◽  
Pupil Constriction ◽  
Sustained Responses ◽  
Stable Control

Rapid and stable control of pupil size in response to light is critical for vision, but the neural coding mechanisms remain unclear. Here, we investigated the neural basis of pupil control by monitoring pupil size across time while manipulating each photoreceptor input or neurotransmitter output of intrinsically photosensitive retinal ganglion cells (ipRGCs), a critical relay in the control of pupil size. We show that transient and sustained pupil responses are mediated by distinct photoreceptors and neurotransmitters. Transient responses utilize input from rod photoreceptors and output by the classical neurotransmitter glutamate, but adapt within minutes. In contrast, sustained responses are dominated by non-conventional signaling mechanisms: melanopsin phototransduction in ipRGCs and output by the neuropeptide PACAP, which provide stable pupil maintenance across the day. These results highlight a temporal switch in the coding mechanisms of a neural circuit to support proper behavioral dynamics.

scholarly journals High-throughput mapping of single-cell molecular and projection architecture of neurons by retrograde barcoded labelling

2021 ◽  
Author(s):  
Peibo Xu ◽  
Jian Peng ◽  
Tingli Yuan ◽  
Zhaoqin Chen ◽  
Ziyan Wu ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Neuron ◽  
Neural Circuit ◽  
Brain Regions ◽  
Mammalian Brain ◽  
Projection Neurons ◽  
Proof Of Concept ◽  
Sequencing Technology ◽  
Modal Data ◽  
Projection Pattern

Deciphering mesoscopic connectivity of the mammalian brain is a pivotal step in neuroscience. Most imaging-based conventional neuroanatomical tracing methods identify area-to-area or sparse single neuronal labeling information. Although recently developed barcode-based connectomics has been able to map a large number of single-neuron projections efficiently, there is a missing link in single-cell connectome and transcriptome. Here, combining single-cell RNA sequencing technology, we established a retro-AAV barcode-based multiplexed tracing method called MEGRE-seq (Multiplexed projEction neuRons retroGrade barcodE), which can resolve projectome and transcriptome of source neurons simultaneously. Using the ventromedial prefrontal cortex (vmPFC) as a proof-of-concept neocortical region, we investigated projection patterns of its excitatory neurons targeting five canonical brain regions, as well as corresponding transcriptional profiles. Dedicated, bifurcated or collateral projection patterns were inferred by digital projectome. In combination with simultaneously recovered transcriptome, we find that certain projection pattern has a preferential layer or neuron subtype bias. Further, we fitted single-neuron two-modal data into a machine learning-based model and delineated gene importance by each projection target. In summary, we anticipate that the new multiplexed digital connectome technique is potential to understand the organizing principle of the neural circuit by linking projectome and transcriptome.

scholarly journals AAV9-Retro Mediates Efficient Transduction with Axon Terminal Absorption and Blood-brain Barrier Transportation

2020 ◽  
Author(s):  
Kunzhang Lin ◽  
Xin Zhong ◽  
Lei Li ◽  
Min Ying ◽  
Tian Yang ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Neural Circuit ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Projection Neurons ◽  
Routes Of Administration ◽  
Functional Studies ◽  
Blood Brain ◽  
Wide Scale ◽  
Alternative Routes

Abstract Recombinant adeno-associated viruses (rAAVs), especially which permit efficient gene transfer to neurons from axonal terminals or across the blood-brain barrier, are useful vehicles for the structural and functional studies of neural circuit, and for the treatment of many gene-deficient brain diseases that needs to compensate for the correct genes to every cell in the whole brain. However, AAVs with these two advantages have not been reported. Here, we describe a new capsid engineering method, which draws on advantage combination of different capsids, and aims to yield a capsid that can provide more alternative routes of administration, which are more suitable for wide-scale transduction of the CNS. A new AAV variant, AAV9-Retro, was developed by inserting the 10-mer peptide fragment from AAV2-Retro into the capsid of AAV9, and the biodistribution properties were evaluated in mice. By intracranial and intravenous injection in the mice, we found that AAV9-Retro can retrogradely infect projection neurons with efficiency comparable to AAV2-Retro, and retains the characteristic of AAV9 that can transport across the nervous system. Our strategy provides a new tool for the manipulation of neural circuits, and for the future preclinical and clinical treatment of some neurological and neurodegenerative disorders.

scholarly journals Predicting how and when hidden neurons skew measured synaptic interactions

2017 ◽  
Author(s):  
Braden A. W. Brinkman ◽  
Fred Rieke ◽  
Eric Shea-Brown ◽  
Michael A. Buice
Keyword(s):  
Neural Coding ◽  
Neural Circuit ◽  
Quantitative Relationship ◽  
Network Size ◽  
Effective Interactions ◽  
Synaptic Interactions ◽  
Neural Computations ◽  
Hidden Neurons ◽  
Circuit Function ◽  
The Impact

AbstractA major obstacle to understanding neural coding and computation is the fact that experimental recordings typically sample only a small fraction of the neurons in a circuit. Measured neural properties are skewed by interactions between recorded neurons and the “hidden” portion of the network. To properly interpret neural data and determine how biological structure gives rise to neural circuit function, we thus need a better understanding of the relationships between measured effective neural properties and the true underlying physiological properties. Here, we focus on how the effective spatiotemporal dynamics of the synaptic interactions between neurons are reshaped by coupling to unobserved neurons. We find that the effective interactions from a pre-synaptic neuronr′to a post-synaptic neuronrcan be decomposed into a sum of the true interaction fromr′torplus corrections from every directed path fromr′torthrough unobserved neurons. Importantly, the resulting formula reveals when the hidden units have—or do not have—major effects on reshaping the interactions among observed neurons. As a particular example of interest, we derive a formula for the impact of hidden units in random networks with “strong” coupling—connection weights that scale with, whereNis the network size, precisely the scaling observed in recent experiments. With this quantitative relationship between measured and true interactions, we can study how network properties shape effective interactions, which properties are relevant for neural computations, and how to manipulate effective interactions.

scholarly journals Effects of short-term plasticity in early olfactory information processing in Drosophila

2021 ◽  
Author(s):  
Yuxuan Liu ◽  
Qianyi Li ◽  
Chao Tang ◽  
Shanshan Qin ◽  
Yuhai Tu
Keyword(s):  
Experimental Data ◽  
Adaptive Response ◽  
Neural Circuit ◽  
Dominant Factor ◽  
Projection Neurons ◽  
Short Term ◽  
Information Process ◽  
Short Term Plasticity ◽  
Olfactory Information ◽  
Divisive Normalization

In Drosophila, olfactory information received by the olfactory receptor neurons (ORNs) is first processed by an incoherent feed forward neural circuit in the antennal lobe (AL) that consists of ORNs (input), the inhibitory local neurons (LNs), and projection neurons (PNs). This "early" olfactory information process has two important characteristics. First, response of a PN to its cognate ORN is normalized by the overall activity of other ORNs, a phenomenon termed "divisive normalization". Second, PNs respond strongly to the onset of ORN activities, but they adapt to prolonged or continuously increasing inputs. Despite the importance of these characteristics for learning and memory, their underlying mechanism remains not fully understood. Here, we develop a circuit model for describing the ORN-LN-PN dynamics by including key features of neuron-neuron interactions, in particular short-term plasticity (STP) and presynaptic inhibition (PI).Our model shows that STP is critical in shaping PN's steady-state response properties. By fitting our model to experimental data quantitatively, we found that strong and balanced short-term facilitation (STF) and short-term depression (STD) in STP is crucial for the observed nonlinear divisive normalization in Drosophila. By comparing our model with the observed adaptive response to time-varying signals quantitatively, we find that both STP and PI contribute to the highly adaptive response with the latter being the dominant factor for a better fit with experimental data. Our model not only helps reveal the mechanisms underlying two main characteristics of the early olfactory process, it can also be used to predict the PN responses to arbitrary time-dependent signals and to infer microscopic properties of the circuit (such as the strengths of STF and STD) from the measured input-output relation.

scholarly journals Analysis of visual processing capabilities and neural coding strategies of a detailed model for laminar cortical microcircuits in mouse V1

2021 ◽  
Author(s):  
Guozhang Chen ◽  
Franz Scherr ◽  
Wolfgang Maass
Keyword(s):  
Visual Processing ◽  
Neural Coding ◽  
Noise Model ◽  
Projection Neurons ◽  
Detailed Model ◽  
Power Law Decay ◽  
Different Types ◽  
Cortical Microcircuits ◽  
Explained Variance ◽  
Spatial Locations

AbstractThe neocortex is a network of rather stereotypical cortical microcircuits that share an exquisite genetically encoded architecture: Neurons of a fairly large number of different types are distributed over several layers (laminae), with specific probabilities of synaptic connections that depend on the neuron types involved and their spatial locations. Most available knowledge about this structure has been compiled into a detailed model [Billeh et al., 2020] for a generic cortical microcircuit in the primary visual cortex, consisting of 51,978 neurons of 111 different types. We add a noise model to the network that is based on experimental data, and analyze the results of network computations that can be extracted by projection neurons on layer 5. We show that the resulting model acquires through alignment of its synaptic weights via gradient descent training the capability to carry out a number of demanding visual processing tasks. Furthermore, this weight-alignment induces specific neural coding features in the microcircuit model that match those found in the living brain: High dimensional neural codes with an arguably close to optimal power-law decay of explained variance of PCA components, specific relations between signal- and noise-coding dimensions, and network dynamics in a critical regime. Hence these important features of neural coding and dynamics of cortical microcircuits in the brain are likely to emerge from aspects of their genetically encoded architecture that are captured by this data-based model in combination with learning processes. In addition, the model throws new light on the relation between visual processing capabilities and details of neural coding.

scholarly journals AAV9-Retro mediates efficient transduction with axon terminal absorption and blood–brain barrier transportation

2020 ◽  
Author(s):  
Kunzhang Lin ◽  
Xin Zhong ◽  
Lei Li ◽  
Min Ying ◽  
Tian Yang ◽  
...  
Keyword(s):  
Nervous System ◽  
Blood Brain Barrier ◽  
Neural Circuit ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Projection Neurons ◽  
Routes Of Administration ◽  
Functional Studies ◽  
Blood Brain ◽  
Alternative Routes

Abstract Recombinant adeno-associated viruses (rAAVs), particularly those that permit efficient gene transfer to neurons from axonal terminals or across the blood–brain barrier, are useful vehicles for structural and functional studies of the neural circuit and for the treatment of many gene-deficient brain diseases that need to compensate for the correct genes in every cell in the whole brain. However, AAVs with these two advantages have not been reported. Here, we describe a new capsid engineering method, which exploits the combination of different capsids and aims to yield a capsid that can provide more alternative routes of administration that are more suitable for the wide-scale transduction of the central nervous system (CNS). A new AAV variant, AAV9-Retro, was developed by inserting the 10-mer peptide fragment from AAV2-Retro into the capsid of AAV9, and the biodistribution properties were evaluated in mice. By intracranial and intravenous injection in the mice, we found that AAV9-Retro can retrogradely infect projection neurons with an efficiency comparable to that of AAV2-Retro and retains the characteristic of AAV9, which can be transported across the nervous system. Our strategy provides a new tool for the manipulation of neural circuits and future preclinical and clinical treatment of some neurological and neurodegenerative disorders.

scholarly journals Transsynaptic Fish-lips signaling prevents misconnections between nonsynaptic partner olfactory neurons

2019 ◽  
Vol 116 (32) ◽  
pp. 16068-16073 ◽  
Author(s):  
Qijing Xie ◽  
Bing Wu ◽  
Jiefu Li ◽  
Chuanyun Xu ◽  
Hongjie Li ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Transmembrane Protein ◽  
Small Subset ◽  
Projection Neurons ◽  
Specific Expression ◽  
Olfactory Neurons ◽  
Surface Molecules ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Receptor Neurons

Our understanding of the mechanisms of neural circuit assembly is far from complete. Identification of wiring molecules with novel mechanisms of action will provide insights into how complex and heterogeneous neural circuits assemble during development. In the Drosophila olfactory system, 50 classes of olfactory receptor neurons (ORNs) make precise synaptic connections with 50 classes of partner projection neurons (PNs). Here, we performed an RNA interference screen for cell surface molecules and identified the leucine-rich repeat–containing transmembrane protein known as Fish-lips (Fili) as a novel wiring molecule in the assembly of the Drosophila olfactory circuit. Fili contributes to the precise axon and dendrite targeting of a small subset of ORN and PN classes, respectively. Cell-type–specific expression and genetic analyses suggest that Fili sends a transsynaptic repulsive signal to neurites of nonpartner classes that prevents their targeting to inappropriate glomeruli in the antennal lobe.

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