Neocortical prodynorphin expression is transiently increased with learning: Implications for time- and learning-dependent neocortical kappa opioid receptor activation

Loh, Ryan; Collins, Sean M.; Galvez, Roberto

doi:10.1016/j.bbr.2017.08.015

Cited by 8 publications

(6 citation statements)

References 36 publications

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“…S2D ). We found that PDyn mRNA was largely restricted to SST mRNA-expressing neurons and sparsely expressed in PV mRNA-expressing neurons, consistent with previous reports ( Loh et al, 2017 , Sohn et al, 2014 , Smith et al, 2019 ). The percentage of Dyn neurons that are VGAT-positive (14.3%) is the same proportion as Dyn neurons that are SST-positive (14.5%), suggesting that SST-positive mPFC Dyn interneurons (mPFC Dyn/SST ) make the overwhelming majority of inhibitory neurons that express PDyn.…”

Section: Resultssupporting

confidence: 93%

Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states

Wang,

Flores,

Yarur

et al. 2024

Preprint

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SummaryPrefrontal cortical (PFC) circuits provide top-down control of threat reactivity. This includes ventromedial PFC (vmPFC) circuitry, which plays a role in suppressing fear-related behavioral states. Dynorphin (Dyn) has been implicated in mediating negative affect and mal-adaptive behaviors induced by severe threats and is expressed in limbic circuits, including the vmPFC. However, there is a critical knowledge gap in our understanding of how vmPFC Dyn-expressing neurons and Dyn transmission detect threats and regulate expression of defensive behaviors. Here, we demonstrate that Dyn cells are broadly activated by threats and release Dyn locally in the vmPFC to limit passive defensive behaviors. We further demonstrate that vmPFC Dyn-mediated signaling promotes a switch of vmPFC networks to a fear-related state. In conclusion, we reveal a previously unknown role of vmPFC Dyn neurons and Dyn neuropeptidergic transmission in suppressing defensive behaviors in response to threats via state-driven changes in vmPFC networks.Highlights●vmPFCDynneurons are activated by threats and threat-predictive cues●Characterization of a genetically-encoded kappa-opioid receptor sensor●vmPFCDynneurons rapidly release Dyn in response to threats and their predictors●vmPFCDynsignaling opposes threat-induced passive defensive behaviors●Dyn signaling promotes threat-evoked state transitions in vmPFC networks

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Section: Resultssupporting

confidence: 93%

Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states

Wang,

Flores,

Yarur

et al. 2024

Preprint

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“…Based on this finding, we cannot exclude the possibility that a small percentage of Pdyn TdTomato neurons recorded were not actively expressing Pdyn. Previous studies indicate that Pdyn + neurons in the cortex are heterogeneous, consisting of both excitatory pyramidal and inhibitory neurons ( Sohn et al, 2014 , Loh et al, 2017 , Smith et al, 2019 ). Immunohistochemistry showed that 24 % of the PL Pdyn+ neurons express glutamate decarboxylase 1 (GAD1/GAD67), which is a molecular marker for GABAergic neurons ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Inhibitory PL Pdyn+ neurons were hypoexcitable 3 days after SNI but at 14 days after SNI we observed an increase in excitability of inhibitory PL Pdyn+ neurons compared to recordings from sham mice. Previous studies report that PL Pdyn+ inhibitory neurons express somatostatin (SOM) ( Sohn et al, 2014 , Loh et al, 2017 , Smith et al, 2019 ). Our lab has reported that spontaneous excitatory synaptic inputs were reduced to L2/3 SOM expressing neurons of the PL in the female mice 7 days after SNI ( Jones and Sheets, 2020 ), which is commonly considered an early time point in chronic neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Mouse models of surgical and neuropathic pain produce distinct functional alterations to prodynorphin expressing neurons in the prelimbic cortex

Zhou

Yin

Sheets

2023

Neurobiology of Pain

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“…In turn, warranting future research. In primary sensory cortices, most PDyn-mRNA expressing neurons are GABAergic somatostatin-containing interneurons ( Sohn et al, 2014 ; Loh et al, 2017b ; Smith et al, 2019 ), whereas, in the PFC, most PDyn-expressing neurons are glutamatergic ( Sohn et al, 2014 ). A recent study using PDyn-iCre mice crossed with tdTomato mice showed strong labeling restricted to superficial layers in the insular cortex ( Pina et al, 2020 ).…”

Section: Neuropeptide Familiesmentioning

confidence: 99%

Neuropeptide System Regulation of Prefrontal Cortex Circuitry: Implications for Neuropsychiatric Disorders

Casello

Flores

Yarur

et al. 2022

Front. Neural Circuits

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Neuropeptides, a diverse class of signaling molecules in the nervous system, modulate various biological effects including membrane excitability, synaptic transmission and synaptogenesis, gene expression, and glial cell architecture and function. To date, most of what is known about neuropeptide action is limited to subcortical brain structures and tissue outside of the central nervous system. Thus, there is a knowledge gap in our understanding of neuropeptide function within cortical circuits. In this review, we provide a comprehensive overview of various families of neuropeptides and their cognate receptors that are expressed in the prefrontal cortex (PFC). Specifically, we highlight dynorphin, enkephalin, corticotropin-releasing factor, cholecystokinin, somatostatin, neuropeptide Y, and vasoactive intestinal peptide. Further, we review the implication of neuropeptide signaling in prefrontal cortical circuit function and use as potential therapeutic targets. Together, this review summarizes established knowledge and highlights unknowns of neuropeptide modulation of neural function underlying various biological effects while offering insights for future research. An increased emphasis in this area of study is necessary to elucidate basic principles of the diverse signaling molecules used in cortical circuits beyond fast excitatory and inhibitory transmitters as well as consider components of neuropeptide action in the PFC as a potential therapeutic target for neurological disorders. Therefore, this review not only sheds light on the importance of cortical neuropeptide studies, but also provides a comprehensive overview of neuropeptide action in the PFC to serve as a roadmap for future studies in this field.

show abstract

Neocortical prodynorphin expression is transiently increased with learning: Implications for time- and learning-dependent neocortical kappa opioid receptor activation

Cited by 8 publications

References 36 publications

Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states

Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states

Mouse models of surgical and neuropathic pain produce distinct functional alterations to prodynorphin expressing neurons in the prelimbic cortex

Neuropeptide System Regulation of Prefrontal Cortex Circuitry: Implications for Neuropsychiatric Disorders

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