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Showing papers by "Sacha B. Nelson published in 2018"


Journal ArticleDOI
TL;DR: Gustatory cortex (GC) is almost certainly a vital part of the circuit that integrates incidental experience into later associative learning, and is investigated to investigate the neurobiology underlying this phenomenon.
Abstract: The strength of learned associations between pairs of stimuli is affected by multiple factors, the most extensively studied of which is prior experience with the stimuli themselves. In contrast, little data is available regarding how experience with "incidental" stimuli (independent of any conditioning situation) impacts later learning. This lack of research is striking given the importance of incidental experience to survival. We have recently begun to fill this void using conditioned taste aversion (CTA), wherein an animal learns to avoid a taste that has been associated with malaise. We previously demonstrated that incidental exposure to salty and sour tastes (taste preexposure-TPE) enhances aversions learned later to sucrose. Here, we investigate the neurobiology underlying this phenomenon. First, we use immediate early gene (c-Fos) expression to identify gustatory cortex (GC) as a site at which TPE specifically increases the neural activation caused by taste-malaise pairing (i.e., TPE did not change c-Fos induced by either stimulus in isolation). Next, we use site-specific infection with the optical silencer Archaerhodopsin-T to show that GC inactivation during TPE inhibits the expected enhancements of both learning and CTA-related c-Fos expression, a full day later. Thus, we conclude that GC is almost certainly a vital part of the circuit that integrates incidental experience into later associative learning.

14 citations


Posted ContentDOI
18 Mar 2018-bioRxiv
TL;DR: In contrast to canonical models of thalamus that suggest it is a switchboard primarily concerned with routing distinct modalities of information to distinct cortical regions, this work shows that the thalamocortical system is more akin to a molecularly-defined ‘filter bank’ repeatedly applied across modality.
Abstract: Uncovering common principles by which diverse modalities of information are processed is a fundamental goal in neuroscience. In mammalian brain, thalamus is the central processing station for inputs from sensory systems, subcortical motor systems, and cortex; a function subserved by over 30 defined nuclei1,2. Multiple thalamic nuclei send convergent information to each region of the forebrain, but whether there is a conserved architecture across the set of thalamic pathways projecting to each forebrain area has remained unresolved3–5. To uncover organizational principles of thalamic pathways, we produced a near-comprehensive transcriptomic atlas of thalamus. This revealed a common logic for thalamic nuclei serving all major cortical modalities. We found that almost all nuclei belong to one of three major profiles, with a given cortical area getting input from each of these profiles. These profiles lie on a single axis of variance aligned with the mediolateral axis of thalamus, and this axis is strongly enriched in genes encoding receptors and ion channels. We further show that each projection profile exhibits different electrophysiological signatures. Single-cell profiling revealed that rather than forming discrete classes, thalamic neurons lie on a spectrum, with intermediate cells existing between profiles. Thus, in contrast to canonical models of thalamus that suggest it is a switchboard primarily concerned with routing distinct modalities of information to distinct cortical regions, we show that the thalamocortical system is more akin to a molecularly-defined ‘filter bank’ repeatedly applied across modality. Together, we reveal striking covariation in the organization of thalamic pathways serving all input modalities and output targets, establishing a simple and comprehensive thalamic functional architecture.

12 citations


Posted ContentDOI
14 Jul 2018-bioRxiv
TL;DR: Gustatory cortex is almost certainly a vital part of the circuit that integrates incidental experience into later associative learning, and is investigated for its role in conditioned taste aversion and incidental exposure to salty and sour tastes.
Abstract: The strength of learned associations between pairs of stimuli is affected by multiple factors, the most extensively studied of which is prior experience with the stimuli themselves. In contrast, little data is available regarding how experience with incidental stimuli (independent of any conditioning situation) impacts later learning. This lack of research is striking given the importance of incidental experience to survival. We have recently begun to fill this void using conditioned taste aversion (CTA), wherein an animal learns to avoid a taste that has been associated with malaise. We previously demonstrated that incidental exposure to salty and sour tastes (taste pre-exposure, TPE) enhances aversions learned later to sucrose. Here, we investigate the neurobiology underlying this phenomenon. First, we use immediate early gene (cFos) expression to identify gustatory cortex (GC) as a site at which TPE specifically increases the neural activation caused by taste-malaise pairing (i.e., TPE did not change cFos induced by either stimulus in isolation). Next, we use site-specific infection with the optical silencer Archaerhodopsin-T to show that GC inactivation during TPE inhibits the expected enhancements of both learning and CTA related cFos expression, a full day later. Thus, we conclude that GC is almost certainly a vital part of the circuit that integrates incidental experience into later associative learning.

Posted ContentDOI
20 Feb 2018-bioRxiv
TL;DR: Together, this analysis shows striking covariation in the organization of thalamic pathways serving all input modalities and output targets, establishing a simple and comprehensiveThalamic functional architecture.
Abstract: Thalamus is the central hub for forebrain communication, a function mediated by approximately 30 nuclei. To uncover organizational principles of the thalamic pathways providing input to the forebrain, we produced a near-comprehensive transcriptomic atlas of its major projection classes. We found that almost all nuclei belong to one of three major profiles that lie on a single axis of variance aligned with the mediolateral axis of thalamus. This axis of variance is strongly enriched in genes encoding receptors and ion channels, and we show that each profile exhibits different electrophysiological signatures. Single-cell profiling revealed even further heterogeneity within established nuclear boundaries, suggesting that the same input to a given nucleus might be differentially processed. Together, our analysis shows striking covariation in the organization of thalamic pathways serving all input modalities and output targets, establishing a simple and comprehensive thalamic functional architecture.