Biology subjects

Rudebeck, P.

Publications and source records attributed to Rudebeck, P..

4 recordsLinked to original sources

bioRxiv2026

Robust and accessible in situ sequencing with an open-source automated sequencer

Targeted in situ sequencing underlies many spatial transcriptomic, barcoded connectomic, and multiplexed perturbation techniques. Each experiment requires many cycles of chemical reactions and imaging that are time-consuming and error-prone to perform manually, and few commercial platforms can sequence highly diverse RNA barcodes in situ at cellular resolution across large tissue sections. Here we present Seq-o-Matic, an open-source automated in situ sequencer built entirely from commercially available components, which integrates fluidics, heated incubation, and imaging of up to three continuous 18 mm x 50 mm areas on standard microscope slides. Relative to manual sequencing, Seq-o-Matic reduced hands-on time 6- to 17.5-fold and total run time about 2.6-fold. Across three runs spanning two mouse strains and a neonatal marmoset, sequencing quality, measured by signal retention, channel specificity, and phasing, was similar to that of four manually sequenced mouse brains. In four mouse hemispheres sequenced in separate runs (two C57BL/6J, one NOD, and one WSB), consensus cell types were present in every brain and corresponded to those of a manually sequenced C57BL/6J brain. Within cortical excitatory neurons, the two C57BL/6J brains were more similar to each other than were brains of different strains, suggesting that technical variation between runs was small relative to strain differences. Seq-o-Matic thus makes consistent, high-throughput in situ sequencing accessible to laboratories without specialized in situ sequencing expertise.

genomics↗

bioRxiv2025

Chemogenetic inhibition of amygdala to ventrolateral prefrontal cortex communication selectively impacts contingent learning

Contingent learning, the process by which specific courses of action become associated with subsequent outcomes, is dependent on the amygdala and ventrolateral prefrontal cortex (vlPFC). The amygdala and vlPFC are bidirectionally connected but it is unclear what the contribution of individual feedforward and feedback pathways is to contingent learning. Here we tested the role of amygdala projections to vlPFC in mediating two key components of contingent learning: signaling the outcome (reward/no reward) that follows a choice and maintaining representation of the choice that was made prior to outcome delivery. To test for these two aspects of contingent learning, we trained macaques to perform a probabilistic reward learning task where for separate stimulus pairs reward was either delivered immediately or after a trace interval. Inhibiting vlPFC-projecting amygdala neurons impacted contingent learning irrespective of whether there was a trace interval or not, and this effect was primarily driven by maladaptive learning on unrewarded trials. Notably, deficits in contingent learning caused by manipulating activity in the amygdala-vlPFC pathway were distinct from impairments in motivation and the ability to update the value of specific rewards in a reinforcer devaluation task. Thus, vlPFC-projecting amygdala neurons appear to play a specific role in contingent learning through signaling the outcomes of a choice, but not in maintaining a memory of the prior choice. SIGNIFICANCE STATEMENTImpairments in learning which stimuli or actions are associated with temporally proximate rewards or punishments is characteristic of a host of psychiatric and neurological disorders. Determining the neural circuits that support this type of contingent learning is therefore a key question in neuroscience. Here we show that that during contingent stimulus-reward learning, projections from amygdala to ventrolateral prefrontal cortex (vlPFC) in macaques are essential for signaling reward delivery or omission. These projections appear to be less involved in maintaining a memory of the prior choice that led to the reward or punishment that is subsequently experienced or for updating the value of the received rewards. Thus, amygdala-vlPFC connections make a specific contribution to signaling reward feedback during learning.

neuroscience↗

bioRxiv2023

The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the macaque amygdala and activated them with a highly selective and potent DREADD agonist, deschloroclozapine. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Interestingly, activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5-14.5Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-disciplinary approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.

neuroscience↗

bioRxiv2020

Temporally-specific sequences of neural activity across interconnected corticolimbic structures during reward anticipation

Functional neuroimaging studies indicate that interconnected parts of the subcallosal anterior cingulate cortex (ACC), striatum, and amygdala play a fundamental role in affect in health and disease. Yet, while the patterns of neural activity engaged in striatum and amygdala during affective processing are well established, especially during reward anticipation, little is known about subcallosal ACC. Here we recorded neural activity in non-human primate subcallosal ACC and compared this to interconnected parts of basolateral amygdala and rostromedial striatum while macaque monkeys performed reward-based tasks. Applying multiple analysis approaches, we found that neurons in subcallosal ACC and rostromedial striatum preferentially signal anticipated reward using short bursts of activity that form temporally specific patterns. By contrast, basolateral amygdala uses a mixture of both temporally specific and more sustained patterns of activity to signal anticipated reward. Thus, dynamic patterns of neural activity across populations of neurons are engaged in affect, especially in subcallosal ACC. HIGHLIGHTSO_LISustained changes in neural activity signal anticipated reward in basolateral amygdala C_LIO_LITemporally specific patterns signal anticipated reward in all areas recorded C_LIO_LINeurons exhibit more punctate encoding when tasks become more complex C_LIO_LITemporally specific patterns of neural activity signal different anticipated rewards in BLA C_LI

neuroscience↗