Distinct neuronal populations contribute to trace conditioning and extinction learning in the hippocampal CA1

Mount, Rebecca A.; Sridhar, Sudiksha; Hansen, Kyle; Mohammed, Ali Ibrahim; Abdulkerim, Moona E; Kessel, Robb; Nazer, Bobak; Gritton, Howard J.; Han, Xue

doi:10.7554/elife.56491

Cited by 17 publications

(8 citation statements)

References 59 publications

(84 reference statements)

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“…36 selectively by one cue in contexts where the cue has become familiar and nonsalient may constitute a kind of extinction trace, as observed in other brain areas. 12,37 Our finding that learned cue responses in POR depend on conjunctions of reward/locomotion contexts builds on prior studies of this region focusing largely on spatial context. 7,8,38,39 Is locomotion truly an internal context in a similar sense as spatial context?…”

Section: Conjunctive Contexts For Cue Learningmentioning

confidence: 59%

Visual association cortex links cues with conjunctions of reward and locomotor contexts

et al. 2022

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Section: Conjunctive Contexts For Cue Learningmentioning

confidence: 59%

Visual association cortex links cues with conjunctions of reward and locomotor contexts

et al. 2022

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“…Consecutive air puffs were separated by 9–11-s intervals (uniform random distribution). The animal’s eye closure response was quantified by measuring the area of the left pupil with an infrared camera (IDIS Co., Ltd., South Korea) at 30 Hz, as previously described [ 74 , 85 , 86 ]. Briefly, raw video images were converted to grayscale images, Gaussian-filtered ( σ = 2 pixels), and thresholded to generate binary masked images.…”

Section: Methodsmentioning

confidence: 99%

Enhanced fear limits behavioral flexibility in Shank2-deficient mice

2022

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Background A core symptom of autism spectrum disorder (ASD) is repetitive and restrictive patterns of behavior. Cognitive inflexibility has been proposed as a potential basis for these symptoms of ASD. More generally, behavioral inflexibility has been proposed to underlie repetitive and restrictive behavior in ASD. Here, we investigated whether and how behavioral flexibility is compromised in a widely used animal model of ASD. Methods We compared the behavioral performance of Shank2-knockout mice and wild-type littermates in reversal learning employing a probabilistic classical trace conditioning paradigm. A conditioned stimulus (odor) was paired with an unconditioned appetitive (water, 6 µl) or aversive (air puff) stimulus in a probabilistic manner. We also compared air puff-induced eye closure responses of Shank2-knockout and wild-type mice. Results Male, but not female, Shank2-knockout mice showed impaired reversal learning when the expected outcomes consisted of a water reward and a strong air puff. Moreover, male, but not female, Shank2-knockout mice showed stronger anticipatory eye closure responses to the air puff compared to wild-type littermates, raising the possibility that the impairment might reflect enhanced fear. In support of this contention, male Shank2-knockout mice showed intact reversal learning when the strong air puff was replaced with a mild air puff and when the expected outcomes consisted of only rewards. Limitations We examined behavioral flexibility in one behavioral task (reversal learning in a probabilistic classical trace conditioning paradigm) using one ASD mouse model (Shank2-knockout mice). Thus, future work is needed to clarify the extent to which our findings (that enhanced fear limits behavioral flexibility in ASD) can explain the behavioral inflexibility associated with ASD. Also, we examined only the relationship between fear and behavioral flexibility, leaving open the question of whether abnormalities in processes other than fear contribute to behavioral inflexibility in ASD. Finally, the neurobiological mechanisms linking Shank2-knockout and enhanced fear remain to be elucidated. Conclusions Our results indicate that enhanced fear suppresses reversal learning in the presence of an intact capability to learn cue-outcome contingency changes in Shank2-knockout mice. Our findings suggest that behavioral flexibility might be seriously limited by abnormal emotional responses in ASD.

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“…ROIs were then manually added to select cells that the machine learning algorithm did not properly identify. ROIs were added as a circle with a radius of 6 pixels (7.8 μm) based on morphology present in the max-min projection image, using the previously-reported semi-automated custom MATLAB software called SemiSeg (github.com/HanLabBU/SemiSeg) 71 .…”

Section: Methodsmentioning

confidence: 99%

“…Onsets of calcium events were identified in each fluorescence trace similarly to previous descriptions 50,71 .…”

Section: Calcium Event Detectionmentioning

confidence: 99%

The autism spectrum disorder risk geneNEXMIFalters hippocampal CA1 cellular and network dynamics

Mount

Athif

O’Connor

et al. 2022

Preprint

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Perturbations in autism spectrum disorder (ASD) risk genes disrupt neural circuit dynamics and ultimately lead to behavioral abnormalities. To understand how ASD-implicated genes influence network computation during behavior, we performed in vivo calcium imaging from hundreds of individual hippocampal CA1 neurons simultaneously in freely locomoting mice with total knockout of NEXMIF. NEXMIF is an ASD risk gene most highly expressed in the hippocampus, and NEXMIF knockout in mice creates a range of behavioral deficits, including impaired hippocampal-dependent memory. We found that NEXMIF knockout does not alter the overall excitability of individual neurons but exaggerates movement-mediated neuronal responses. At the network level, NEXMIF knockout creates over-synchronization of the CA1 circuit, quantified by pairwise correlation and network closeness centrality. These neuronal effects observed upon NEXMIF knockout highlight the network consequences of perturbations in ASD-implicated genes, which have broad implications for cognitive performance and other ASD-related behavioral disruptions.

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Distinct neuronal populations contribute to trace conditioning and extinction learning in the hippocampal CA1

Cited by 17 publications

References 59 publications

Visual association cortex links cues with conjunctions of reward and locomotor contexts

Visual association cortex links cues with conjunctions of reward and locomotor contexts

Enhanced fear limits behavioral flexibility in Shank2-deficient mice

The autism spectrum disorder risk geneNEXMIFalters hippocampal CA1 cellular and network dynamics

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