Biology subjects

Hammond, L. A.

Publications and source records attributed to Hammond, L. A..

5 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↗

bioRxiv2022

A brain atlas of the camouflaging dwarf cuttlefish, Sepia bandensis

The coleoid cephalopods (cuttlefish, octopus, and squid) are a group of soft-bodied marine mollusks that exhibit an array of interesting biological phenomena, including dynamic camouflage, complex social behaviors, prehensile regenerating arms, and large brains capable of learning, memory, and problem-solving [1-10]. The dwarf cuttlefish, Sepia bandensis, is a promising model cephalopod species due to its small size, substantial egg production, short generation time, and dynamic social and camouflage behaviors [11]. Cuttlefish dynamically camouflage to their surroundings by changing the color, pattern and texture of their skin. Camouflage is optically-driven, and is achieved by expanding and contracting hundreds of thousands of pigment-filled saccules (chromatophores) in the skin, which are controlled by motor neurons emanating from the brain. We generated a dwarf cuttlefish brain atlas using magnetic resonance imaging (MRI), deep learning, and histology, and we built an interactive web tool (cuttlebase.org) to host the data. Guided by observations in other cephalopods [12-20], we identified 32 brain lobes, including two large optic lobes (75% the total volume of the brain), chromatophore lobes whose motor neurons directly innervate the chromatophores of the color-changing skin, and a vertical lobe that has been implicated in learning and memory. This brain atlas provides a valuable tool for exploring the neural basis of cuttlefish behavior.

neuroscience↗

bioRxiv2021

Tools for efficient analysis of neurons in a 3D reference atlas of whole mouse spinal cord

Spinal neurons are highly heterogeneous in location, transcriptional identity and function. To understand their contributions to sensorimotor circuits, it is essential to map the positions of identified subsets of neurons in relation to others throughout the spinal cord (SC), but we lack tools for whole SC sample preparation, imaging and in toto analysis. To overcome this problem, we have (1) designed scaffolds (SpineRacks) that facilitate efficient and ordered cryo-sectioning of the entire SC in a single block, (2) constructed a 3D reference atlas of adult mouse SC and (3) developed software (SpinalJ) to register images of sections and for standardized analysis of cells and projections in atlas space. We have verified mapping accuracies for known neurons and demonstrated the usefulness of this platform to reveal unknown neuronal distributions. Together, these tools provide high-throughput analyses of whole mouse SC and enable direct comparison of 3D spatial information between animals and studies.

neuroscience↗

bioRxiv2019

Integrins protect nociceptive neurons in models of paclitaxel-mediated peripheral sensory neuropathy

Chemotherapy induced peripheral neuropathy (CIPN) is a major side effect from cancer treatment with no known method for prevention or cure in clinics. CIPN primarily affects unmyelinated nociceptive sensory terminals. Despite the high prevalence of CIPN, molecular and cellular mechanisms that lead to CIPN are still poorly understood. Here, we used a genetically tractable Drosophila model and primary sensory neurons isolated from adult mouse to examine the mechanisms underlying CIPN and identify protective pathways. We found that chronic treatment of Drosophila larvae with paclitaxel caused sensory neuron degeneration, altered the terminal branching pattern of nociceptive neurons, and reduced thermal nociceptive responses. We found that nociceptive neuron-specific overexpression of integrins, which are known to support neuronal maintenance in several systems, conferred protection from paclitaxel-mediated cellular and behavioral phenotypes. Live imaging and superresolution approaches provide evidence that paclitaxel treatment causes cellular changes that are consistent with alterations in endosome-mediated trafficking of integrins. We used primary dorsal root ganglia neuron cultures to test conservation of integrin-mediated protection. We show that overexpression of a human integrin {beta} subunit 1 (ITGB1) also prevented degeneration following paclitaxel treatment. Altogether, our study supports conserved mechanisms of paclitaxel-induced perturbation of integrin trafficking and a therapeutic potential of restoring integrin levels to antagonize paclitaxel-mediated toxicity in sensory neurons.

neuroscience↗

bioRxiv2019

An amygdala circuit mediates experience-dependent momentary exploratory arrests

Exploration of novel environments ensures survival and evolutionary fitness. This behavior is expressed through exploratory bouts and arrests, which change dynamically based on experience. Neural circuits mediating exploratory behavior should therefore integrate experience and use it to select the proper behavioral output. Using a spatial exploration assay, we uncovered an experience-dependent increase of momentary arrests in visited locations where animals previously arrested. Quantitative analyses of neuronal calcium activity in freely-exploring mice revealed that a large neuronal ensemble in basolateral amygdala is active during self-paced behavioral arrests. This ensemble was recruited in an experience-dependent manner, and closed-loop optogenetic manipulation of these neurons revealed that they are sufficient and necessary to drive experience-dependent arrests. Additionally, we found that neurons in the basolateral amygdala projecting to central amygdala mediate these momentary arrests. These findings uncover an amygdala circuit that mediates momentary exploratory arrests in familiar places, without changing place preference or anxiety/fear-like behaviors.

neuroscience↗