Ensemble encoding of conditioned fear by prefrontal somatostatin interneurons

Cummings, Kirstie A.; Bayshtok, Sabina; Kenny, Paul J.; Clem, Roger L.

doi:10.1101/2021.07.18.452791

Cited by 4 publications

(5 citation statements)

References 48 publications

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“…Furthermore, recent research has shown that cortical spike timing dependent plasticity of PV+ interneuron-mediated inhibition contributes to auditory map remodeling (Vickers et al, 2018). Similarly, prefrontal SST+ interneurons have been reported to encode fear memory (Cummings and Clem, 2020;Cummings et al, 2022). Although we did not thoroughly investigate the mechanisms underlying fear memory-mediated long-term inhibitory synaptic plasticity, our results indicate that the frequency of mIPSCs were potentiated by fear memory, predominantly in PKC-δ(+) neurons.…”

Section: Discussionmentioning

confidence: 61%

“…The role of inhibitory engrams is currently debated (Josselyn and Tonegawa, 2020). So far, engrams formed by inhibitory neurons have been mostly studied in circuits expressing both glutamatergic and GABAergic cells (Cummings and Clem, 2020;Cummings et al, 2022). In this context, GABAergic engram neurons have been proposed to play a role in keeping the balance or controlling the extension of glutamatergic excitatory engrams (Barron et al, 2017;Josselyn and Tonegawa, 2020;Rao-Ruiz et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

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Inhibitory fear memory engram in the mouse central lateral amygdala

Hou,

Jariwala,

Wang

et al. 2023

Preprint

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SUMMARYEngrams are cellular substrates of memory traces that have been identified in various brain areas, including the amygdala. Most engrams identified so far are formed by excitatory, glutamatergic neurons. However, little attention has been paid to defining GABAergic inhibitory engrams. Here, we report an inhibitory engram in the central lateral amygdala (CeL), a crucial area for Pavlovian fear conditioning. This engram is primarily composed of GABAergic somatostatin-expressing (SST+) and to a lesser extent of protein kinase C-δ-expressing [PKC-δ(+)] neurons. Fear memory is accompanied by a preferential enhancement of mIPSC frequency onto PKC-δ(+) neurons as well as a general increment of amplitude. Moreover, non-engram cells exhibit higher mIPSC frequency than engram cells. The inhibition of the CeL GABAergic engram disinhibits the activity of engram-targeted areas and increases selectively the encoded fear expression. Our data defines the behavioral function of an engram formed exclusively by GABAergic inhibitory neurons in the mammalian CNS.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Inhibitory fear memory engram in the mouse central lateral amygdala

Hou,

Jariwala,

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…3E, H). Limited Oprm1 was found in somatostatin (Sst) and vasoactive intestinal polypeptide (Vip) GABAergic interneurons (79,80). To localize putative nociceptive celltypes, we used two measures of noxious-evoked IEGs-a weighted distribution 'activity score' and IEG density mapping with Nebulosa of n=25 IEGs (Fig.…”

Section: Cingulate Cartography Of Opioidergic and Nociceptive Cell-typesmentioning

confidence: 99%

Mimicking opioid analgesia in cortical pain circuits

James,

McCall,

Hsu

et al. 2024

Preprint

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The anterior cingulate cortex plays a pivotal role in the cognitive and affective aspects of pain perception. Both endogenous and exogenous opioid signaling within the cingulate mitigate cortical nociception, reducing pain unpleasantness. However, the specific functional and molecular identities of cells mediating opioid analgesia in the cingulate remain elusive. Given the complexity of pain as a sensory and emotional experience, and the richness of ethological pain-related behaviors, we developed a standardized, deep-learning platform for deconstructing the behavior dynamics associated with the affective component of pain in mice, LUPE (Light aUtomated Pain Evaluator). LUPE removes human bias in behavior quantification and accelerated analysis from weeks to hours, which we leveraged to discover that morphine altered attentional and motivational pain behaviors akin to affective analgesia in humans. Through activity-dependent genetics and single-nuclei RNA sequencing, we identified specific ensembles of nociceptive cingulate neuron-types ex-pressing mu-opioid receptors. Tuning receptor expression in these cells bidirectionally modulated morphine analgesia. Moreover, we employed a synthetic opioid receptor promoter-driven approach for cell-type specific optical and chemical genetic viral therapies to mimic morphine's pain-relieving effects in the cingulate, without reinforcement. This approach offers a novel strategy for precision pain management by targeting a key nociceptive cortical circuit with on-demand, non-addictive, and effective analgesia.

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“…In an assay stimulating cultured neurons, E-SARE has demonstrated higher reporter expression levels and a dynamic range compared to the c-Fos promoter ( Kawashima et al, 2013 ). E-SARE was used to label activated neurons in cortex ( Kawashima et al, 2013 ; Cummings et al, 2021 ) and hippocampus ( Attardo et al, 2018 ).…”

Section: Advances In Activity-dependent Gene Expressing Systemsmentioning

confidence: 99%

Molecular tools to capture active neural circuits

Onishi,

Hirose,

Sakaba

2024

Front. Neural Circuits

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To understand how neurons and neural circuits function during behaviors, it is essential to record neuronal activity in the brain in vivo. Among the various technologies developed for recording neuronal activity, molecular tools that induce gene expression in an activity-dependent manner have attracted particular attention for their ability to clarify the causal relationships between neuronal activity and behavior. In this review, we summarize recently developed activity-dependent gene expression tools and their potential contributions to the study of neural circuits.

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Ensemble encoding of conditioned fear by prefrontal somatostatin interneurons

Cited by 4 publications

References 48 publications

Inhibitory fear memory engram in the mouse central lateral amygdala

Inhibitory fear memory engram in the mouse central lateral amygdala

Mimicking opioid analgesia in cortical pain circuits

Molecular tools to capture active neural circuits

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