Biology subjects

Tanno, S.

Publications and source records attributed to Tanno, S..

6 recordsLinked to original sources

bioRxiv2026

Thalamocortical credit routing from the basal ganglia and cerebellum: anatomical constraints and circuit principles

Animals learn to select actions that maximize reward in complex environments. A central challenge in this process is credit routing: behavioral outcomes must be routed back to the neural populations that contributed to generating the relevant actions. One possible route is through thalamocortical pathways conveying learning signals from the basal ganglia and cerebellum, where plasticity is shaped by reward-prediction errors. However, how these pathways route such signals back to specific cortical circuits remains unclear. To address this question, we combined anatomical circuit mapping in mice with closed-loop circuit modeling. Anterograde transsynaptic tracing revealed that thalamic neurons receiving input from the substantia nigra pars reticulata or the lateral cerebellar nucleus were largely segregated, with partial overlap in the ventromedial thalamus. Nevertheless, their cortical axons shared a pronounced enrichment in layer 1a, most prominently in secondary motor cortex. In a brain- wide synergistic loop-circuit model, learning was enhanced when both pathways delivered additive and gain-modulating feedback aligned with the cortical action readout. Local activity- based calibration established this alignment, whereas dendritic-spike- and reward-prediction- error-dependent thalamocortical plasticity further refined behavioral output. Module-specific feedback was essential for a brain-machine interface task requiring the simultaneous conditioning of multiple target neurons. Together, these findings define a credit-routing architecture in which laminar convergence, plastic alignment, and modular feedback link parallel subcortical learning systems to cortical action representations.

neuroscience↗

bioRxiv2024

Dynamic integration of cortical activity in the deep layer of the anterolateral superior colliculus

The superior colliculus (SC) receives inputs from various brain regions in a layer- and radial location-specific manner, but whether the SC exhibits location-specific dynamics remains unclear. To address this issue, we recorded the spiking activity of single SC neurons while photoactivating cortical areas in awake head-fixed Thy1-ChR2 rats. We classified 309 neurons that responded significantly into 8 clusters according to the response dynamics. Among them, neurons with monophasic excitatory responses (7-12 ms latency) that returned to baseline within 20 ms were commonly observed in the optic and intermediate gray layers of centromedial and centrolateral SC. In contrast, neurons with complex polyphasic responses were commonly observed in the deep layers of the anterolateral SC. Cross-correlation analysis suggested that the complex pattern could be only partly explained by an internal circuit of the deep gray layer. Our results indicate that medial to centrolateral SC neurons simply relay cortical activity, whereas neurons in the deep layers of the anterolateral SC dynamically integrate inputs from the cortex, SNr, CN, and local circuits. These findings suggest a spatial gradient in SC integration, with a division of labor between simple relay circuits and those integrating complex dynamics.

neuroscience↗

bioRxiv2024

Synergistic reinforcement learning by cooperation of the cerebellum and basal ganglia

The cerebral cortex, cerebellum and basal ganglia are essential for flexible learning in mammals. Although traditionally thought to operate under different learning rules, recent evidence suggests that both the basal ganglia and the cerebellum may employ reinforcement learning mechanisms. This raises the question of how these structures coordinate when a common reward prediction error mechanism is active. To address this issue, we first examined output signals from the basal ganglia and cerebellum following the activity of the cerebral cortex. We recorded single-neuron activity from the output regions of the cerebellum and basal ganglia - the cerebellar nuclei (CN) and substantia nigra pars reticulata (SNr) - in both male and female ChR2 transgenic rats. Neurons in the CN and SNr exhibited distinct temporal response patterns; notably, the fast excitatory response in the CN, driven by mossy fiber input, was synchronized with the inhibitory response in the SNr, mediated via the direct pathway. Using these experimental findings together with connectome data, we developed both a semi-realistic spiking network model and a reservoir-based reinforcement learning model. In the latter model, successful learning depended on synaptic plasticity in both the cerebellum and basal ganglia with a temporal precision on the order of 10 ms. Furthermore, cortical {beta}-oscillations enhanced learning and optimal reinforcement learning occurred when the output of cerebellar and basal ganglia signal phase-locked at the frequency of cortical oscillation. Taken together, our results suggest that the coordinated output of the cerebellum and basal ganglia, driven by tightly tuned cortical input, underlies brain-wide synergistic reinforcement learning. Significance StatementThe cerebral cortex, cerebellum, and basal ganglia support learning. Recent research suggests that both the basal ganglia and cerebellum use a similar learning process called reinforcement learning, which involves predicting rewards. To understand how these brain regions work together, we recorded brain activity in rats while photo-stimulating the cerebral cortex. We found that two types of responses in the cerebellum and basal ganglia were synchronized, which might help activate the cerebral cortex. A computer model showed that precise timing of signals from both the cerebellum and basal ganglia is important for learning. This timing was important only when the cerebral cortex worked in a specific frequency range. Our findings suggest that coordinated brain activity enhances learning.

neuroscience↗

bioRxiv2024

HIV broadly neutralizing antibody escapability drives the therapeutic efficacy of vectored immunotherapy

Broadly neutralizing antibodies (bNAbs) have shown promise for prevention and treatment of HIV. Potency and breadth measured in vitro are often used as predictors of clinical potential; however, human studies demonstrate that clinical efficacy of bNAbs can be undermined by both pre-existing and de novo resistance. Here we find that HIV-infected humanized mice receiving bNAbs delivered via AAV as Vectored ImmunoTherapy (VIT) can be used to identify antibody escape paths, which are largely conserved for each bNAb. Path selection, and consequent therapeutic success, is driven by the fitness cost and resistance benefit of emerging mutations. Applying this framework, we independently modulated bNAb resistance or the fitness cost of escape mutants, resulting in enhanced efficacy of VIT. This escape path analysis successfully explains the therapeutic efficacy of bNAbs, and enables a tractable means of quantifying and comparing the potential for viral escape from therapeutics in vivo. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/603156v4_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@180c86borg.highwire.dtl.DTLVardef@1e6108dorg.highwire.dtl.DTLVardef@148bac7org.highwire.dtl.DTLVardef@1de93ca_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2022

Antibody-mediated prevention of vaginal HIV transmission is dictated by IgG subclass in humanized mice

HIV broadly neutralizing antibodies (bNAbs) are capable of both blocking viral entry and recruiting innate immunity to HIV-infected cells through their fragment crystallizable (Fc) region. Vaccination or productive infection results in a polyclonal mixture of class-switched IgG antibodies comprised of four subclasses, each encoding distinct Fc regions that differentially engage innate immune functions. Despite evidence that innate immunity contributes to protection, the relative contribution of individual IgG subclasses is unknown. Here we use vectored immunoprophylaxis (VIP) in humanized mice to interrogate the efficacy of individual IgG subclasses during prevention of vaginal HIV transmission by VRC07, a potent CD4-binding site directed bNAb. We find that VRC07-IgG2, which lacks Fc-mediated functionality, exhibits significantly reduced protection in vivo relative to other subclasses. However, even low concentrations of highly functional VRC07-IgG1 yields substantial protection against vaginal challenge, suggesting that interventions capable of eliciting modest titers of functional subclasses may provide meaningful benefit against infection.

immunology↗

bioRxiv2021

TAILORED DC INDUCE PROTECTIVE HIV-1 SPECIFIC POLYFUNCTIONAL CD8+ T CELLS IN THE LYMPHOID TISSUE FROM HUMANIZED BLT MICE

Effective function of CD8+ T cells and enhanced innate activation of dendritic cells (DC) in response to HIV-1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK-binding Kinase 1 (TBK1) might be useful to acquire controller-like properties. Here, we evaluated the impact of TBK1-primed DC inducing protective CD8+ T cell responses in lymphoid tissue and peripheral blood and their association with reduced HIV-1 disease progression in vivo in the humanized bone marrow, liver and thymus (hBLT) mouse model. A higher proportion of hBLT-mice vaccinated with TBK1-primed DC exhibited less severe CD4+ T cell depletion following HIV-1 infection compared to control groups. This was associated with infiltration of CD8+ T cells in the white pulp from the spleen, reduced spread of infected p24+ cells to secondary lymphoid organs and with preserved abilities of CD8+ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, TBK1-primed DC might be an useful tool for subsequent vaccine studies. Author summaryEmulating protective immunological characteristics from individuals capable of spontaneously controlling HIV-1 infection might be useful for the development of a protective vaccine. Enhanced function of dendritic cells (DC) in these HIV-1 controllers depends on the activation of TANK-binding Kinase 1 (TBK1) and might associate with protective T cells. Our study evaluated the ability of DCs trained through TBK1 activation inducing protective adaptive immune responses against HIV-1 and reducing disease progression in vivo, using a humanized mouse model. Our data indicate that mice vaccinated with tailored DC exhibit delayed disease progression, increased induction of protective CD8+ T lymphocyte subsets in the lymphoid tissue and blood upon antigen recognition. Therefore, trained-DC might be an useful tool for future HIV-1 vaccine designs.

immunology↗