Biology subjects

Griggs, N.

Publications and source records attributed to Griggs, N..

3 recordsLinked to original sources

bioRxiv2026

Deep conservation of head direction circuits in bees, ants and flies

To navigate, animal brains must continuously estimate the bodys heading in space and compare it with internal goals to guide movement. In the fruit fly Drosophila melanogaster a neural circuit in the central complex of the brain serves as an internal compass, exploiting a network architecture called a ring attractor1, 2. While this region is highly conserved and involved in navigation in many insects3, 4, it remains unclear whether the fly circuit represents a general blueprint for head direction computation, or whether different ecologies have driven distinct circuit solutions. Using synaptic-resolution circuit mapping, we identified homologous head direction networks in bees and ants and compared them to the fly circuit. We show that the insect head direction network is conserved across at least 300 million years of evolution. At the level of cell types and projection patterns, all studied species share a nearly identical neural layout, both qualitatively and quantitatively. At the synaptic level, however, the fly and bee circuits differed fundamentally. The distinct wiring principles of homologous neurons expose highly evolvable elements within this otherwise stable circuit. Using these differences in circuit architecture to constrain computational models, we show that both the bee and fly circuits can effectively function as ring attractors with similar, yet distinct, properties. These results demonstrate that complex neural circuits can remain stable over many hundreds of millions of years, while still offering access points for evolution to flexibly adjust neural computations to changing ecological demands, illustrating how evolution balances stability and flexibility in brain circuits.

neuroscience↗

bioRxiv2025

μ-Opioid Receptor Superagonists Engage a Sodium-Bound Active State

The simple two-state conformational selection model of G-protein coupled receptor (GPCR) activation suggests that, by binding to a high affinity site, an agonist will shift receptor equilibrium in favor of active state (R*) conformations that recruit heterotrimeric G proteins over inactive state (R) conformations. Agonist binding to the -opioid receptor is highly sensitive to Na+ ions which stabilize an inactive receptor state. Higher efficacy opioid agonists, such as DAMGO and fentanyl, are sensitive to Na+ compared to lower efficacy ligands at the -opioid receptor. However, the binding of the highly potent oripavine agonists etorphine and dihydroetorphine are less sensitive to Na+ than expected such that the prevailing models fail to explain their pharmacology. To explain this discrepancy, experiments were performed to evaluate the binding properties and G protein activation of the highly potent agonists carfentanil, BU72, etorphine, etonitazene and similarly potent opioid peptidomimetics in comparison to the standard agonists DAMGO, fentanyl, and morphine in the presence or absence of Na+ or K+ ions. Several of the superagonists retained high affinity and potency in both ionic conditions, whereas DAMGO, fentanyl and morphine displayed enhanced binding and signaling in K+, compared to Na+ ions. These functional parameters were used to determine an intrinsic efficacy value, determined as [Formula]. Comparison of affinity shifts with intrinsic efficacy afforded a negative correlation in which superagonists with the highest intrinsic efficacy are least sensitive to Na+. These data suggest that select -opioid receptor superagonists have high affinity for the Na+ bound receptor states (R) and shift these species into active receptor conformations (R*) that efficiently couple to G proteins. Significance StatementThe simple theory of conformational selection suggests the binding affinities of high efficacy -opioid receptor ligands, such as fentanyl and DAMGO, are more sensitive to Na+ and guanine nucleotide which stabilize inactive receptor states than lower efficacy agonists and antagonists. Here, we show that ligands with high intrinsic efficacy (superagonists) are much less sensitive to Na+ and guanine nucleotide. This work demonstrates that highly potent ligands can engage a low affinity Na+-bound receptor state that may then convert to a receptor species that efficiently couples to G protein - i.e. a conformational induction.

pharmacology and toxicology↗

bioRxiv2025

Distributed control circuits across a brain-and-cord connectome

Just as genomes revolutionized molecular genetics, connectomes (maps of neurons and synapses) are transforming neuroscience. To date, the only species with complete connectomes are worms1-3 and sea squirts4 (103-104 synapses). By contrast, the fruit fly is more complex (108 synaptic connections), with a brain that supports learning and spatial memory5,6 and an intricate ventral nerve cord analogous to the vertebrate spinal cord7-11. Here we report the first densely reconstructed adult fly connectome that unites the brain and ventral nerve cord, and we leverage this resource to investigate principles of neural control. We show that effector neurons (motor neurons, endocrine cells and efferent neurons targeting the viscera) are primarily influenced by sensory neurons in the same body part, forming local feedback loops. These local loops are linked by long-range circuits involving ascending and descending neurons organized into behavior-centric modules. Single ascending and descending neurons are often positioned to influence the voluntary movements of multiple body parts, together with the endocrine cells or visceral organs that support those movements. Brain regions involved in learning and navigation supervise these circuits. These results reveal an architecture that is distributed, parallelized and embodied, reminiscent of distributed control architectures in engineered systems12,13.

neuroscience↗