Biology subjects

Liu, L. D.

Publications and source records attributed to Liu, L. D..

7 recordsLinked to original sources

bioRxiv2026

MHC restriction is structurally encoded by the T cell receptor germline

MHC restriction -- the requirement for {beta} T cell receptors (TCRs) to recognize Major Histocompatibility Complex (MHC) molecules when presenting peptide antigens -- is a pillar of adaptive immunity. Here, we provide direct structural evidence for TCR germline-encoded recognition of MHC molecules irrespective of antigenic peptide. We engineered "germline-like" TCRs to eliminate CDR3 specificity for peptide, and a molecular clamping strategy to trap ultra-low-affinity complexes with peptide-MHC for cryo-EM. We find that germline-like TCR/pMHC docking modes are identical to wild-type T cell receptors with intact CDR3 loops, across distinct peptide antigens and MHC alleles. Analysis of human TCR repertoires reveals enrichment of specific V genes and V-V{beta} pairing patterns associated with HLA-A*02 contexts. Thus, the TCR germline encodes the blueprint for MHC restriction, providing a sequence-based framework that could inform computational and AI-driven prediction of TCR specificity.

immunology↗

bioRxiv2025

Decision signals in the absence of spiking activity in primate visual cortex

Fluctuations in single-neuron activity in sensory cortex often correlate with perceptual decisions. This kind of correlation has been hypothesized to reflect a causal influence of sensory signals on decisions, a feedback influence of decisions on sensory signals, and various other factors as well. To disentangle these different possibilities, we have examined local field potentials (LFPs) recorded from the middle temporal (MT) area of non-human primates performing a motion discrimination task. Compared to single-neuron spiking, LFPs have the advantage of being decomposable into different frequencies that are associated with different anatomical sources of input. More importantly, they persist when spiking activity is inactivated, which precludes a causal influence of the corresponding neural activity on behavior. We found that high frequency (70-150 Hz) LFP power was correlated with perceptual decisions and that this correlation disappeared when spikes were inactivated, consistent with a causal role for this frequency band in decision making. These signals overlapped in time with decision signals in lower gamma-band power (30-70 Hz), which persisted after spiking inactivation, suggesting a non-causal, feedback input. Interestingly, lower-frequency LFP signals (5-30 Hz) reflected both impending perceptual decisions and the outcome of previous trials. Our results therefore reveal that neural activity multiplexes different sources of information about perceptual decisions and that these types of information can be estimated reliably from different LFP frequencies.

neuroscience↗

bioRxiv2025

A brainstem map of orofacial rhythms

Rhythmic orofacial movements, such as eating, drinking, or vocalization, are controlled by distinct premotor oscillator networks in the brainstem. Orofacial movements must be coordinated with rhythmic breathing to avoid aspiration and because they share muscles. Understanding how brainstem circuits coordinate rhythmic motor programs requires neurophysiological measurements in behaving animals. We used Neuropixels probe recordings to map brainstem neural activity related to breathing, licking, and swallowing in mice drinking water. Breathing and licking rhythms were tightly coordinated and phase-locked, whereas intermittent swallowing paused breathing and licking. Multiple clusters of neurons, each recruited during different orofacial rhythms, delineated a lingual premotor network in the intermediate nucleus of the reticular formation (IRN). Local optogenetic perturbation experiments identified a region in the IRN where constant stimulation can drive sustained rhythmic licking, consistent with a central pattern generator for licking. Stimulation to artificially induce licking showed that coupled brainstem oscillators autonomously coordinated licking and breathing. The brainstem oscillators were further patterned by descending inputs at moments of licking initiation. Our results reveal the logic governing interactions of orofacial rhythms during behavior and outline their neural circuit dynamics, providing a model for dissecting multi-oscillator systems controlling rhythmic motor programs.

neuroscience↗

bioRxiv2023

Decision-related activity and movement selection in primate visual cortex

Fluctuations in the activity of sensory neurons often predict perceptual decisions. This connection can be quantified with a metric called choice probability (CP), and there has been a longstanding debate about whether CP reflects a causal influence on decisions, or an echo of decision-making activity elsewhere in the brain. Here we show that CP can actually reflect a third variable, namely the movement used to indicate the decision. In a standard visual motion discrimination task, neurons in the middle temporal (MT) area of the primate visual cortex responded more strongly during trials in which the animals executed a saccade toward their receptive fields, and less strongly for saccades directed away from the receptive fields. The resulting trial-to-trial variability accounted for much of the CP observed across the neuronal population, and it arose through training. Surprisingly, the learned association between MT activity and oculomotor selection was causal, as pharmacological inactivation of MT neurons biased behavioral responses away from the corresponding receptive field locations. These results demonstrate that training on a task with fixed sensorimotor contingencies introduces movement-related activity in sensory brain regions, and that this plasticity can shape the neural circuitry of perceptual decision-making.

animal behavior and cognition↗

bioRxiv2023

Brain-wide neural activity underlying memory-guided movement

Behavior requires neural activity across the brain, but most experiments probe neurons in a single area at a time. Here we used multiple Neuropixels probes to record neural activity simultaneously in brain-wide circuits, in mice performing a memory-guided directional licking task. We targeted brain areas that form multi-regional loops with anterior lateral motor cortex (ALM), a key circuit node mediating the behavior. Neurons encoding sensory stimuli, choice, and actions were distributed across the brain. However, in addition to ALM, coding of choice was concentrated in subcortical areas receiving input from ALM, in an ALM-dependent manner. Choice signals were first detected in ALM and the midbrain, followed by the thalamus, and other brain areas. At the time of movement initiation, choice-selective activity collapsed across the brain, followed by new activity patterns driving specific actions. Our experiments provide the foundation for neural circuit models of decision-making and movement initiation.

neuroscience↗

bioRxiv2020

Accurate localization of linear probe electrodes across multiple brains

Recently developed silicon probes have large numbers of recording electrodes on long linear shanks. Specifically, Neuropixels probes have 960 recording electrodes distributed over 9.6 mm shanks. Because of their length, Neuropixels probe recordings in rodents naturally span multiple brain areas. Typical studies collate recordings across several recording sessions and animals. Neurons recorded in different sessions and animals have to be aligned to each other and to a standardized brain coordinate system. Here we report a workflow for accurate localization of individual electrodes in standardized coordinates and aligned across individual brains. This workflow relies on imaging brains with fluorescent probe tracks and warping 3-dimensional image stacks to standardized brain atlases. Electrophysiological features are then used to anchor particular electrodes along the reconstructed tracks to specific locations in the brain atlas and therefore to specific brain structures. We performed ground-truth experiments, in which motor cortex outputs are labelled with ChR2 and a fluorescence protein. Recording from brain regions targeted by these outputs reveals better than 100 m accuracy for electrode localization.

neuroscience↗

bioRxiv2017

A unifying motif for spatial and directional surround suppression

In the visual system, the response to a stimulus in a neurons receptive field can be modulated by stimulus context, and the strength of these contextual influences vary with stimulus intensity. Recent work has shown how a theoretical model, the stabilized supralinear network (SSN), can account for such modulatory influences, using a small set of computational mechanisms. While the predictions of the SSN have been confirmed in primary visual cortex (V1), its computational principles apply with equal validity to any cortical structure. We have therefore tested the generality of the SSN by examining modulatory influences in the middle temporal area (MT) of the macaque visual cortex, using electrophysiological recordings and pharmacological manipulations. We developed a novel stimulus that can be adjusted parametrically to be larger or smaller in the space of all possible motion directions. We found, as predicted by the SSN, that MT neurons integrate across motion directions for low-contrast stimuli, but that they exhibit suppression by the same stimuli when they are high in contrast. These results are analogous to those found in visual cortex when stimulus size is varied in the space domain. We further tested the mechanisms of inhibition using pharmacologically manipulations of inhibitory efficacy. As predicted by the SSN, local manipulation of inhibitory strength altered firing rates, but did not change the strength of surround suppression. These results are consistent with the idea that the SSN can account for modulatory influences along different stimulus dimensions and in different cortical areas.\n\nSignificance StatementVisual neurons are selective for specific stimulus features in a region of visual space known as the receptive field, but can be modulated by stimuli outside of the receptive field. The SSN model has been proposed to account for these and other modulatory influences, and tested in V1. As this model is not specific to any particular stimulus feature or brain region, we wondered whether similar modulatory influences might be observed for other stimulus dimensions and other regions. We tested for specific patterns of modulatory influences in the domain of motion direction, using electrophysiological recordings from MT. Our data confirm the predictions of the SSN in MT, suggesting that the SSN computations might be a generic feature of sensory cortex.

neuroscience↗