Biology subjects

Leyton, M.

Publications and source records attributed to Leyton, M..

5 recordsLinked to original sources

bioRxiv2026

Memory erasure by dopamine-gated retrospective learning

Erasing outdated memories is crucial for adaptive behavior. Yet once a cue-outcome association is learned, repeated cue exposure without outcome suppresses conditioned behavior without erasing the underlying memory. This allows rapid behavioral recovery when outcomes are reintroduced. Here, we confirm this limitation for standard "prospective extinction" protocols that present cues without the associated outcome, but show that true memory erasure is achieved by inverting the paradigm: presenting outcomes without associated cues, i.e., "retrospective extinction". We demonstrate that orbitofrontal cortex activity at outcome is necessary for the rapid behavioral recovery following prospective extinction, and that mesolimbic dopamine activity at outcome is necessary for retrospective extinction. These findings reconceptualize extinction mechanisms and suggest complementary strategies to mitigate relapse and erase maladaptive memories.

neuroscience↗

bioRxiv2025

Inter-individual variability of neurotransmitter receptor and transporter density in the human brain

Neurotransmitter receptors guide the propagation of signals between brain regions. Mapping receptor distributions in the brain is therefore necessary for understanding how neurotransmitter systems mediate the link between brain structure and function. Normative receptor density can be estimated using group averages from Positron Emission Tomography (PET) imaging. However, the generalizability and reliability of group-average receptor maps depends on the inter-individual variability of receptor density, which is currently unknown. Here we collect group standard deviation brain maps of PET-estimated protein abundance for 12 different neurotransmitter receptors and transporters across 7 neurotransmitter systems, including dopamine, serotonin, acetylcholine, glutamate, GABA, cannabinoid, and opioid. We illustrate how cortical and subcortical inter-individual variability of receptor and transporter density varies across brain regions and across neurotransmitter systems. We complement inter-individual variability with inter-regional variability, and show that receptors that vary more across brain regions than across individuals also demonstrate greater out-of-sample spatial consistency. Altogether, this work quantifies how receptor systems vary in healthy individuals, and provides a means of assessing the generalizability of PET-derived receptor density quantification.

neuroscience↗

bioRxiv2022

Multimodal, multiscale connectivity blueprints of the cerebral cortex

The brain is composed of disparate neural populations that communicate and interact with one another. Although fiber bundles, similarities in molecular architecture, and synchronized neural activity all represent brain connectivity, a comprehensive study of how all these connectivity modes jointly reflect brain structure and function remains missing. Here we systematically integrate seven multimodal, multiscale brain connectivity profiles derived from gene expression, neurotransmitter receptor density, cellular morphology, glucose metabolism, haemodynamic activity, and electrophysiology. We uncover a compact set of universal organizational principles through which brain geometry and neuroanatomy shape emergent connectivity modes. Connectivity modes also exhibit unique and diverse connection patterns, hub profiles, dominant gradients, and modular organization. Throughout, we observe a consistent primacy of molecular connectivity modes--namely correlated gene expression and receptor similarity--that map well onto multiple phenomena including the rich club and patterns of cortical abnormalities across 13 neurological, psychiatric, and neurodevelopmental disorders. Finally, we fuse all seven connectivity modes into a single multimodal network and show that it maps onto major organizational features of the brain including structural conenctivity, intrinsic functional networks, and cytoarchitectonic classes. Altogether, this work contributes to next-generation connectomics and the integrative study of inter-regional relationships.

neuroscience↗

bioRxiv2021

Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macroscale neuroanatomy and how they shape emergent function remains poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from >1 200 healthy individuals to construct a whole-brain 3-D normative atlas of 19 receptors and transporters across 9 different neurotransmitter systems. We find that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncover a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we find both expected and novel associations between receptor distributions and cortical thinning patterns across 13 disorders. We replicate all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization.

neuroscience↗

bioRxiv2018

Dopamine signaling modulates the stability and integration of intrinsic brain networks

Dopaminergic projections are hypothesized to stabilize neural signaling and neural representations, but how they shape regional information processing and large-scale network interactions remains unclear. Here we investigated effects of lowered dopamine levels on within-region temporal signal variability (measured by sample entropy) and between-region functional connectivity (measured by pairwise temporal correlations) in the healthy brain at rest. The acute phenylalanine and tyrosine depletion (APTD) method was used to decrease dopamine synthesis in 51 healthy participants who underwent resting-state functional MRI (fMRI) scanning. Functional connectivity and regional signal variability were estimated for each participant. Multivariate partial least squares (PLS) analysis was used to statistically assess changes in signal variability following APTD as compared to the balanced control treatment. The analysis captured a pattern of increased regional signal variability following dopamine depletion. Changes in hemodynamic signal variability were concomitant with changes in functional connectivity, such that nodes with greatest increase in signal variability following dopamine depletion also experienced greatest decrease in functional connectivity. Our results suggest that dopamine may act to stabilize neural signaling, particularly in networks related to motor function and orienting attention towards behaviorally-relevant stimuli. Moreover, dopaminedependent signal variability is critically associated with functional embedding of individual areas in large-scale networks.

neuroscience↗