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14 Janelia Publications
Showing 1-10 of 14 resultsMating and egg laying are tightly cooordinated events in the reproductive life of all oviparous females. Oviposition is typically rare in virgin females but is initiated after copulation. Here we identify the neural circuitry that links egg laying to mating status in Drosophila melanogaster. Activation of female-specific oviposition descending neurons (oviDNs) is necessary and sufficient for egg laying, and is equally potent in virgin and mated females. After mating, sex peptide-a protein from the male seminal fluid-triggers many behavioural and physiological changes in the female, including the onset of egg laying. Sex peptide is detected by sensory neurons in the uterus, and silences these neurons and their postsynaptic ascending neurons in the abdominal ganglion. We show that these abdominal ganglion neurons directly activate the female-specific pC1 neurons. GABAergic (γ-aminobutyric-acid-releasing) oviposition inhibitory neurons (oviINs) mediate feed-forward inhibition from pC1 neurons to both oviDNs and their major excitatory input, the oviposition excitatory neurons (oviENs). By attenuating the abdominal ganglion inputs to pC1 neurons and oviINs, sex peptide disinhibits oviDNs to enable egg laying after mating. This circuitry thus coordinates the two key events in female reproduction: mating and egg laying.
How nicotine exposure produces long-lasting changes that remodel neural circuits with addiction is unknown. Here, we report that long-term nicotine exposure alters the trafficking of α4β2-type nicotinic acetylcholine receptors (α4β2Rs) by dispersing and redistributing the Golgi apparatus. In cultured neurons, dispersed Golgi membranes were distributed throughout somata, dendrites and axons. Small, mobile vesicles in dendrites and axons lacked standard Golgi markers and were identified by other Golgi enzymes that modify glycans. Nicotine exposure increased levels of dispersed Golgi membranes, which required α4β2R expression. Similar nicotine-induced changes occurred in vivo at dopaminergic neurons at mouse nucleus accumbens terminals, consistent with these events contributing to nicotine’s addictive effects. Characterization in vitro demonstrated that dispersal was reversible, that dispersed Golgi membranes were functional, and that membranes were heterogenous in size, with smaller vesicles emerging from larger “ministacks”, similar to Golgi dispersal induced by nocadazole. Protocols that increased cultured neuronal synaptic excitability also increased Golgi dispersal, without the requirement of α4β2R expression. Our findings reveal novel activity- and nicotine-dependent changes in neuronal intracellular morphology. These changes regulate levels and location of dispersed Golgi membranes at dendrites and axons, which function in local trafficking at subdomains.
The ability to measure synaptic connectivity and properties is essential for understanding neuronal circuits. However, existing methods that allow such measurements at cellular resolution are laborious and technically demanding. Here, we describe a system that allows such measurements in a high-throughput way by combining two-photon optogenetics and volumetric Ca2+ imaging with whole-cell recording. We reveal a circuit motif for generating fast undulatory locomotion in zebrafish.
Connections between neuronal populations may be genetically hardwired or random. In the insect olfactory system, projection neurons of the antennal lobe connect randomly to Kenyon cells of the mushroom body. Consequently, while the odor responses of the projection neurons are stereotyped across individuals, the responses of the Kenyon cells are variable. Surprisingly, downstream of Kenyon cells, mushroom body output neurons show stereotypy in their responses. We found that the stereotypy is enabled by the convergence of inputs from many Kenyon cells onto an output neuron, and does not require learning. The stereotypy emerges in the total response of the Kenyon cell population using multiple odor-specific features of the projection neuron responses, benefits from the nonlinearity in the transfer function, depends on the convergence:randomness ratio, and is constrained by sparseness. Together, our results reveal the fundamental mechanisms and constraints with which convergence enables stereotypy in sensory responses despite random connectivity.
Long-term memory depends on the control of activity-dependent neuronal gene expression, which is regulated by epigenetic modifications. The epigenetic modification of histones is orchestrated by the opposing activities of two classes of regulatory complexes: permissive co-activators and silencing co-repressors. Much work has focused on co-activator complexes, but little is known about the co-repressor complexes that suppress the expression of plasticity-related genes. Here, we define a critical role for the co-repressor SIN3A in memory and synaptic plasticity, showing that postnatal neuronal deletion of Sin3a enhances hippocampal long-term potentiation and long-term contextual fear memory. SIN3A regulates the expression of genes encoding proteins in the post-synaptic density. Loss of SIN3A increases expression of the synaptic scaffold Homer1, alters the mGluR1α- and mGluR5-dependence of long-term potentiation, and increases activation of extracellular signal regulated kinase (ERK) in the hippocampus after learning. Our studies define a critical role for co-repressors in modulating neural plasticity and memory consolidation and reveal that Homer1/mGluR signaling pathways may be central molecular mechanisms for memory enhancement.
Animals avoid predators and find the best food and mates by learning from the consequences of their behavior. However, reinforcers are not always uniquely appetitive or aversive but can have complex properties. Most intoxicating substances fall within this category; provoking aversive sensory and physiological reactions while simultaneously inducing overwhelming appetitive properties. Here we describe the subtle behavioral features associated with continued seeking for alcohol despite aversive consequences. We developed an automated runway apparatus to measure how Drosophila respond to consecutive exposures of a volatilized substance. Behavior within this Behavioral Expression of Ethanol Reinforcement Runway (BEER Run) demonstrated a defined shift from aversive to appetitive responses to volatilized ethanol. Behavioral metrics attained by combining computer vision and machine learning methods, reveal that a subset of 9 classified behaviors and component behavioral features associate with this shift. We propose this combination of 9 be
Nervous systems have the ability to select appropriate actions and action sequences in response to sensory cues. The circuit mechanisms by which nervous systems achieve choice, stability and transitions between behaviors are still incompletely understood. To identify neurons and brain areas involved in controlling these processes, we combined a large-scale neuronal inactivation screen with automated action detection in response to a mechanosensory cue in Drosophila larva. We analyzed behaviors from 2.9x105 larvae and identified 66 candidate lines for mechanosensory responses out of which 25 for competitive interactions between actions. We further characterize in detail the neurons in these lines and analyzed their connectivity using electron microscopy. We found the neurons in the mechanosensory network are located in different regions of the nervous system consistent with a distributed model of sensorimotor decision-making. These findings provide the basis for understanding how selection and transition between behaviors are controlled by the nervous system.
3-photon excitation enables in vivo fluorescence microscopy deep in densely labeled and highly scattering samples, while maintaining high resolution and contrast. We designed and characterized a dual-plane 3-photon microscope with temporal multiplexing and remote focusing, and performed simultaneous in vivo calcium imaging of two planes deep in the cortex of a transgenic mouse expressing GCaMP6s in nearly all excitatory neurons.
We review recent progress in neural probes for brain recording, with a focus on the Neuropixels platform. Historically the number of neurons’ recorded simultaneously, follows a Moore’s law like behavior, with numbers doubling every 6.7 years. Using traditional techniques of probe fabrication, continuing to scale up electrode densities is very challenging. We describe a custom CMOS process technology that enables electrode counts well beyond 1000 electrodes; with the aim to characterize large neural populations with single neuron spatial precision and millisecond timing resolution. This required integrating analog and digital circuitry with the electrode array, making it a standalone integrated electrophysiology recording system. Input referred noise and power per channel is 7.5µV and <50µW respectively to ensure tissue heating <1°C. This approach enables doubling the number of measured neurons every 12 months.
Here we design and optimize a genetically encoded fluorescent indicator, iAChSnFR, for the ubiquitous neurotransmitter acetylcholine, based on a bacterial periplasmic binding protein. iAChSnFR shows large fluorescence changes, rapid rise and decay kinetics, and insensitivity to most cholinergic drugs. iAChSnFR revealed large transients in a variety of slice and in vivo preparations in mouse, fish, fly and worm. iAChSnFR will be useful for the study of acetylcholine in all animals.