Biology subjects

Maimon, G.

Publications and source records attributed to Maimon, G..

10 recordsLinked to original sources

bioRxiv2025

Drosophila maintain a consistent navigational goal angle for days to weeks

Past work has demonstrated that Drosophila can keep to a consistent navigational bearing for minutes to hours. Here, we ask whether they can do so over days to weeks. First, we describe an experimental rig that allows individual head-fixed Drosophila to live for at least two weeks within a virtual-reality environment. Flies walk on a spherical treadmill and receive sugar drops at defined moments as food. Individuals express robust circadian and sleep rhythms on these rigs. We further show that flies freely navigating an environment containing a single visual orienting cue (akin to the sun) will often pick a unique direction and walk forward along that direction for tens to hundreds of meters over days to weeks. This preferred direction can be considered a goal angle because individuals will repeatedly correct for experimentally induced virtual rotations away from this angle. Flies rely on the visual cue to effectively progress forward along the goal angle--walking in circles without it--and they return to walking forward along the same angle in the morning after spending a full night (twelve hours) in darkness without the cue. These results argue for the existence of navigation goals in the Drosophila brain with a persistence time of days to weeks. Furthermore, the technology introduced here may enable trained behaviors across thousands of reinforcement trials in Drosophila, a paradigm central to mammalian neuroscience yet absent in flies.

neuroscience↗

bioRxiv2024

A green lifetime biosensor for calcium that remains bright over its full dynamic range

Fluorescent biosensors toggle between two states and for the vast majority of biosensors one state is bright and the other state is dim. As a consequence, there is a substantial difference in the signal-to-noise ratio (SNR) for the two states. The dim state has a low signal-to-noise ratio, which is problematic when precise, quantitative measurements are needed. During the engineering of a red-shifted variant of an mTurquoise-based calcium sensor, we serendipitously generated a green-emitting sensor that shows high brightness in both the calcium-bound and -unbound state, while still showing a calcium dependent lifetime change of >1 nanosecond. This sensor, named G-Ca-FLITS, is comparable in brightness to the bright state of GCaMP3 and jGCaMP7c in mammalian cells. The calcium induced loss in fluorescence intensity is only around 30% and therefore we observe little variation in the SNR when calcium levels change. G-Ca-FLITS shows negligible sensitivity to pH in the physiological range, like its turquoise parent. Using fluorescence lifetime imaging (FLIM), we measured the calcium concentration with G-Ca-FLITS in various organelles and observed in HeLa cells transient and spatially heterogeneous calcium elevations in mitochondria. Finally, we evaluated the use of G-Ca-FLITS and its turquoise predecessor for two-photon FLIM in Drosophila brains. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/622032v2_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@1caf016org.highwire.dtl.DTLVardef@586996org.highwire.dtl.DTLVardef@7c15cdorg.highwire.dtl.DTLVardef@7b6f03_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

Neuronal calcium spikes enable vector inversion in the Drosophila brain

A typical neuron signals to downstream cells when it is depolarized and firing sodium spikes. Some neurons, however, also fire calcium spikes when hyperpolarized. The function of such bidirectional signaling remains unclear in most circuits. Here we show how a neuron class that participates in vector computation in the fly central complex employs hyperpolarization-elicited calcium spikes to invert two-dimensional mathematical vectors. By switching from firing sodium to calcium spikes, these neurons implement a [~]180{degrees} realignment between the vector encoded in the neuronal population and the flys internal compass signal, thus inverting the vector. We show that the calcium spikes rely on the T-type calcium channel Ca-1T, and argue, via analytical and experimental approaches, that these spikes enable vector computations in portions of angular space that would otherwise be inaccessible. These results reveal a seamless interaction between molecular, cellular and circuit properties for implementing vector mathematics in the brain.

neuroscience↗

bioRxiv2022

Converting an allocentric goal into an egocentric steering signal

Neuronal signals relevant for spatial navigation have been described in many species1-12, however, a circuit-level understanding of how such signals interact to guide behaviour is lacking. Here we characterize a neuronal circuit in the Drosophila central complex that compares internally generated estimates of the flys heading and goal angles--both encoded in world-centred, or allocentric, coordinates--to generate a body-centred, or egocentric, steering signal. Past work has argued that the activity of EPG cells, or "compass neurons"2, represents the flys moment-to-moment angular orientation, or heading angle, during navigation13. An animals moment-to-moment heading angle, however, is not always aligned with its goal angle, i.e., the allocentric direction in which it wishes to progress forward. We describe a second set of neurons in the Drosophila brain, FC2 cells14, with activity that correlates with the flys goal angle. Furthermore, focal optogenetic activation of FC2 neurons induces flies to orient along experimenter-defined directions as they walk forward. EPG and FC2 cells connect monosynaptically to a third neuronal class, PFL3 cells14,15. We found that individual PFL3 cells show conjunctive, spike-rate tuning to both heading and goal angles during goal-directed navigation. Informed by the anatomy and physiology of these three cell classes, we develop a formal model for how this circuit can compare allocentric heading- and goal-angles to build an egocentric steering signal in the PFL3 output terminals. Quantitative analyses and optogenetic manipulations of PFL3 activity support the model. The biological circuit described here reveals how two, population-level, allocentric signals are compared in the brain to produce an egocentric output signal appropriate for the motor system.

neuroscience↗

bioRxiv2021

An internal expectation guides Drosophila egg-laying decisions

When presented with two egg-laying substrates, Drosophila lay most of their eggs on the option with higher relative value. How do flies make this relative-value decision? Might the strategy they use allow them to choose the best option even when they experience substrates with a more complex spatiotemporal profile than in canonical two-choice paradigms? We measured Drosophila egg-laying behavior in diverse substrate environments. In all cases, we found that flies dynamically increase or decrease their egg-laying rates as they explore substrates for a deposition site so as to target eggs to the best, recently visited option. Visiting the best option typically led to a strong reduction in egg laying on other substrates for several minutes, with this timescale varying across fly strains. Our data support a model in which flies compare the value of the current substrate with an internally constructed expectation on the value of available options to regulate the likelihood of laying an egg. We show that dopamine-neuron activity is critical for learning and/or expressing this expectation, similar to its role in certain tasks in vertebrates. Integrating sensory experiences over minutes to generate an internal sense of the quality of available options, i.e., forming an expectation, allows flies to use a dynamic reference point for judging the current substrate and might be a general way in which decisions are made, even beyond flies and egg laying.

neuroscience↗

bioRxiv2021

A rise-to-threshold signal for a relative value deliberation

Whereas progress has been made in identifying neural signals related to rapid, cued decisions1-4, less is known about how brains guide and terminate more ethologically relevant deliberations, where an animals own behavior governs the options experienced over minutes5-8. Drosophila search for many seconds to minutes for egg-laying sites with high relative value9, 10 and neurons, called oviDNs, exist whose activity fulfills necessity and sufficiency criteria for initiating the egg-deposition motor program11. Here we show that oviDNs express a calcium signal that rises over seconds to minutes as a fly deliberates whether to lay an egg. The calcium signal dips when an egg is internally prepared (ovulated), rises at a rate related to the relative value of the current substrate being experienced, and reaches a consistent peak just prior to the abdomen bend for egg deposition. We provide perturbational evidence that the egg-deposition motor program is initiated once this signal hits a threshold and that sub-threshold variation in the signal regulates the time spent deliberating and, ultimately, the option chosen. These results argue that a rise-to-threshold signal guides Drosophila to lay eggs on substrate options with high relative value, with each egg-laying event representing a self-paced decision similar to real-world decisions made by humans and other mammals.

neuroscience↗

bioRxiv2020

A neuronal circuit for vector computation builds an allocentric traveling-direction signal in the Drosophila fan-shaped body

Many behavioral tasks require the manipulation of mathematical vectors, but, outside of computational models1-8, it is not known how brains perform vector operations. Here we show how the Drosophila central complex, a region implicated in goal-directed navigation8-14, performs vector arithmetic. First, we describe neural signals in the fan-shaped body that explicitly track a flys allocentric traveling direction, that is, the traveling direction in reference to external cues. Past work has identified neurons in Drosophila12,15-17 and mammals18,19 that track allocentric heading (e.g., head-direction cells), but these new signals illuminate how the sense of space is properly updated when traveling and heading angles differ. We then characterize a neuronal circuit that rotates, scales, and adds four vectors related to the flys egocentric traveling direction-- the traveling angle referenced to the body axis--to compute the allocentric traveling direction. Each two-dimensional vector is explicitly represented by a sinusoidal activity pattern across a distinct neuronal population, with the sinusoids amplitude representing the vectors length and its phase representing the vectors angle. The principles of this circuit, which performs an egocentric-to-allocentric coordinate transformation, may generalize to other brains and to domains beyond navigation where vector operations or reference-frame transformations are required.

neuroscience↗

bioRxiv2020

Transforming representations of movement from body- to world-centric space

When an animal moves through the world, its brain receives a stream of information about the bodys translational movement. These incoming movement signals, relayed from sensory organs or as copies of motor commands, are referenced relative to the body. Ultimately, such body-centric movement signals must be transformed into world-centric coordinates for navigation1. Here we show that this computation occurs in the fan-shaped body in the Drosophila brain. We identify two cell types in the fan-shaped body, PFNd and PFNv2,3, that conjunctively encode translational velocity signals and heading signals in walking flies. Specifically, PFNd and PFNv neurons form a Cartesian representation of body-centric translational velocity - acquired from premotor brain regions4,5 - that is layered onto a world-centric heading representation inherited from upstream compass neurons6-8. Then, we demonstrate that the next network layer, comprising h{Delta}B neurons, is wired so as to transform the representation of translational velocity from body-centric to world-centric coordinates. We show that this transformation is predicted by a computational model derived directly from electron microscopy connectomic data9. The model illustrates the key role of a specific network motif, whereby the PFN neurons that synapse onto the same h{Delta}B neuron have heading-tuning differences that offset the differences in their preferred body-centric directions of movement. By integrating a world-centric representation of travel velocity over time, it should be possible for the brain to form a working memory of the path traveled through the environment10-12.

neuroscience↗

bioRxiv2019

SPARC: a method to genetically manipulate precise proportions of cells.

Many experimental approaches rely on controlling gene expression in select subsets of cells within an individual animal. However, reproducibly targeting transgene expression to specific fractions of a genetically-defined cell-type is challenging. We developed Sparse Predictive Activity through Recombinase Competition (SPARC), a generalizable toolkit that can express any effector in precise proportions of post-mitotic cells in Drosophila. Using this approach, we demonstrate targeted expression of many effectors and apply these tools to calcium imaging of individual neurons and optogenetic manipulation of sparse cell populations in vivo.

neuroscience↗

bioRxiv2018

Walking Drosophila aim to maintain a neural heading estimate at an internal goal angle

While navigating their environment, many animals track their angular heading via the activity of heading-sensitive neurons. How internal heading estimates are used to guide navigational behavior, however, remains largely unclear in any species. We found that normal synaptic output from heading neurons in Drosophila is required for flies to stably maintain their trajectory along an arbitrary direction while navigating a simple virtual environment. We further found that if the heading estimate carried by these neurons is experimentally redirected by focal stimulation, the fly typically turns so as to rotate this internal heading estimate back towards the initial angle, while also slowing down until this correction has been made. These experiments argue that flies compare an internal heading estimate with an internal goal angle to guide navigational decisions, highlighting an important computation underlying how a spatial variable in the brain is translated into navigational action.\n\nOne Sentence SummaryFlies compare an internal heading estimate with an internal goal angle to guide navigation.

neuroscience↗