Biology subjects

Khalili, A.

Publications and source records attributed to Khalili, A..

4 recordsLinked to original sources

bioRxiv2026

The External Globus Pallidus is a Basal Ganglia Output Hub with Action-Specific Circuits

The external globus pallidus (GPe) is traditionally viewed as a homogeneous relay in the indirect basal ganglia pathway that broadly suppresses movement. Using whole-brain anterograde axon mapping, rabies tracing, single-neuron reconstruction, and single-nucleus RNA sequencing, we reveal that the GPe is a major basal ganglia output nucleus, composed of anatomically and molecularly distinct populations. Besides the neurons with canonical projections, and projections to striatum and cortex, the GPe contains specific neuronal populations that target the thalamus and brainstem directly, including the parafascicular thalamus (GPePf) and the pedunculopontine nucleus (GPePPN). These projection-defined subpopulations exhibit distinct behavioral functions. GPe-PPN neurons are selectively suppressed at locomotor onset, and bidirectional manipulation of this pathway is sufficient to promote or suppress locomotion. Notably, D2-MSN stimulation upstream of these neurons evokes locomotion, and co-activation of GPePPN pathway blocks this D2-MSN-evoked locomotion, demonstrating a disinhibitory circuit for action stemming from D2-MSNs. In contrast, GPePf neurons are not engaged during locomotion but are selectively recruited during skilled forelimb actions, and their activation disrupts forelimb movements without affecting locomotion. Together, these findings establish the GPe as a basal ganglia output hub composed of modules that mediate distinct behaviors. This organization revises canonical models of the indirect pathway by demonstrating that D2-MSNs can also facilitate, rather than only suppress, movement depending on the downstream GPe output channels they engage. In briefThe external globus pallidus (GPe), classically considered a relatively homogeneous relay within the indirect basal ganglia pathway, is revealed here as a major basal ganglia output hub. Distinct GPe subpopulations, defined by transcriptomic identity and projection target, form parallel channels to cortical, thalamic and brainstem structures with action-specific functions. These findings uncover a disinhibitory mechanism through which D2-MSNs can facilitate behavior, revising canonical models of basal ganglia function. HighlightsBrain-wide mapping reveals the GPe as a major basal ganglia output node GPe contains novel cell types defined by transcriptomic identity and projection specificity Projection-specific GPe circuits differentially control locomotion and skilled forelimb actions D2-MSNs can disinhibit downstream targets via specific GPe projections and promote action.

neuroscience↗

bioRxiv2024

A neural circuit for context-dependent multimodal signaling in Drosophila

Many animals, including humans, produce multimodal displays by combining acoustic with visual or vibratory signals [1-4]. However, the neural circuits that coordinate the production of multiple signals in a context-dependent manner are unknown. Multimodal behaviors could be produced by parallel circuits that independently integrate the external cues that trigger each signal. We find that multimodal signals in Drosophila are driven by a single circuit that integrates external sensory cues with internal motivational state and circuit dynamics. Drosophila males produce air-borne song and substrate-borne vibration during courtship and previous studies have identified neurons that drive courtship and singing, but the contexts and circuits that drive vibrations and coordinate multimodal signaling were not known [5-11]. We show that males produce song and vibration in distinct, largely non-overlapping contexts and that brain neurons that drive song also drive vibrations with cell-type specific dynamics and via separate pre-motor pathways. This circuit also coordinates multimodal signaling with ongoing behavior, namely locomotion, to drive vibrations only when the males vibrations can reach the female. A shared circuit facilitates the control of signal dynamics by external cues and motivational state through shared mechanisms like recurrence and mutual inhibition. A proof-of-concept circuit model shows that these motifs are sufficient to explain the behavioral dynamics. Our work shows how simple motifs can be combined in a single neural circuit to select and coordinate multiple behaviors.

neuroscience↗

bioRxiv2023

Rethinking sinking: Imaging the flow fields of natural marine aggregates to derive sinking velocity

The marine biological carbon pump is mainly driven by the interplay between aggregate sinking velocity and remineralization. Sinking velocity of natural marine aggregates is not routinely measured but often calculated using Stokes law, which does not consider size-dependent changes in porosity. We analyzed the flow fields around 81 in situ-formed aggregates using Particle Image Velocimetry (PIV) to determine the factors controlling aggregate settling. Using an independently derived scaling of porosity with size, we predicted the sinking velocity of laboratory-formed and in situ-formed aggregates with known densities. Small aggregates (<500 {micro}m) have relatively lower porosities than large aggregates, and their increased compactness and density leads to higher size-specific settling velocities, and generally higher carbon-to-volume ratios. Applying our scaling approach to a global data set of vertical aggregate abundance and size distribution, we found that small aggregates contribute 40-70% to total carbon fluxes in situ. TeaserImproved sinking velocity prediction for marine aggregates highlights the contribution of small aggregates to carbon sequestration.

biophysics↗

bioRxiv2021

A neuromorphic model of olfactory processing and sparse coding in the Drosophila larva brain

Animal nervous systems are highly efficient in processing sensory input. The neuromorphic computing paradigm aims at the hardware implementation of neural network computations to support novel solutions for building brain-inspired computing systems. Here, we take inspiration from sensory processing in the nervous system of the fruit fly larva. With its strongly limited computational resources of <200 neurons and <1.000 synapses the larval olfactory pathway employs fundamental computations to transform broadly tuned receptor input at the periphery into an energy efficient sparse code in the central brain. We show how this approach allows us to achieve sparse coding and increased separability of stimulus patterns in a spiking neural network, validated with both software simulation and hardware emulation on mixed-signal real-time neuromorphic hardware. We verify that feedback inhibition is the central motif to support sparseness in the spatial domain, across the neuron population, while the combination of spike frequency adaptation and feedback inhibition determines sparseness in the temporal domain. Our experiments demonstrate that such small-sized, biologically realistic neural networks, efficiently implemented on neuromorphic hardware, can achieve parallel processing and efficient encoding of sensory input at full temporal resolution.

neuroscience↗