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• W3099103659 endingPage "100267" @default.
• W3099103659 startingPage "100267" @default.
• W3099103659 abstract "The lateral habenula (LHb) is an epithalamic brain region associated with value-based decision making and stress evasion through its modulation of dopamine (DA)-mediated reward circuitry. Specifically, increased activity of the LHb is associated with drug addiction, schizophrenia and stress-related disorders such as depression, anxiety and posttraumatic stress disorder. Dynorphin (Dyn)/Kappa opioid receptor (KOR) signaling is a mediator of stress response in reward circuitry. Previously, we have shown that maternal deprivation (MD), a severe early life stress, increases LHb spontaneous neuronal activity and intrinsic excitability while blunting the response of LHb neurons to extrahypothalamic corticotropin-releasing factor (CRF) signaling, another stress mediator. CRF pathways also interact with Dyn/KOR signaling. Surprisingly, there has been little study of direct KOR regulation of the LHb despite its distinct role in stress, reward and aversion processing. To test the functional role of Dyn/KOR signaling in the LHb, we utilized ex-vivo electrophysiology combined with pharmacological tools in rat LHb slices. We show that activation of KORs by a KOR agonist (U50,488) exerted differential effects on the excitability of two distinct sub-populations of LHb neurons that differed in their expression of hyperpolarization-activated cation currents (HCN, Ih). Specifically, KOR stimulation increased neuronal excitability in LHb neurons with large Ih currents (Ih+) while decreasing neuronal excitability in small/negative Ih (Ih-) neurons. We found that an intact fast-synaptic transmission was required for the effects of U50,488 on the excitability of both Ih- and Ih+ LHb neuronal subpopulations. While AMPAR-, GABAAR-, or NMDAR-mediated synaptic transmission alone was sufficient to mediate the effects of U50,488 on excitability of Ih- neurons, either GABAAR- or NMDAR-mediated synaptic transmission could mediate these effects in Ih+ neurons. Consistently, KOR activation also altered both glutamatergic and GABAergic synaptic transmission where stimulation of presynaptic KORs uniformly suppressed glutamate release onto LHb neurons while primarily decreased or in some cases increased GABA release. We also found that MD significantly increased immunolabeled Dyn (the endogenous KOR agonist) labeling in neuronal fibers in LHb while significantly decreasing mRNA levels of KORs in LHb tissues compared to those from non-maternally deprived (non-MD) control rats. Moreover, the U50,488-mediated increase in LHb neuronal firing observed in non-MD rats was absent following MD. Altogether, this is the first demonstration of the existence of functional Dyn/KOR signaling in the LHb that can be modulated in response to severe early life stressors such as MD." @default.
• W3099103659 created "2020-11-23" @default.
• W3099103659 creator A5022801712 @default.
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• W3099103659 creator A5084186413 @default.
• W3099103659 date "2020-11-01" @default.
• W3099103659 modified "2023-10-02" @default.
• W3099103659 title "Early life stress dysregulates kappa opioid receptor signaling within the lateral habenula" @default.
• W3099103659 cites W1409281047 @default.
• W3099103659 cites W1492717422 @default.
• W3099103659 cites W1520271859 @default.
• W3099103659 cites W1593533288 @default.
• W3099103659 cites W1650998670 @default.
• W3099103659 cites W1978818986 @default.
• W3099103659 cites W1979031324 @default.
• W3099103659 cites W1979351012 @default.
• W3099103659 cites W1982068079 @default.
• W3099103659 cites W1991236735 @default.
• W3099103659 cites W1993417422 @default.
• W3099103659 cites W2010305307 @default.
• W3099103659 cites W2012111567 @default.
• W3099103659 cites W2013001152 @default.
• W3099103659 cites W2015290667 @default.
• W3099103659 cites W2017552726 @default.
• W3099103659 cites W2018126125 @default.
• W3099103659 cites W2020278649 @default.
• W3099103659 cites W2022367291 @default.
• W3099103659 cites W2023757802 @default.
• W3099103659 cites W2031926980 @default.
• W3099103659 cites W2033205472 @default.
• W3099103659 cites W2035587441 @default.
• W3099103659 cites W2037654275 @default.
• W3099103659 cites W2038159735 @default.
• W3099103659 cites W2041074598 @default.
• W3099103659 cites W2045811240 @default.
• W3099103659 cites W2045927851 @default.
• W3099103659 cites W2049319643 @default.
• W3099103659 cites W2049791338 @default.
• W3099103659 cites W2053012680 @default.
• W3099103659 cites W2057942500 @default.
• W3099103659 cites W2061593240 @default.
• W3099103659 cites W2062106032 @default.
• W3099103659 cites W2062682953 @default.
• W3099103659 cites W2070624459 @default.
• W3099103659 cites W2078234731 @default.
• W3099103659 cites W2088840267 @default.
• W3099103659 cites W2090759875 @default.
• W3099103659 cites W2091536928 @default.
• W3099103659 cites W2091939203 @default.
• W3099103659 cites W2092375927 @default.
• W3099103659 cites W2092774614 @default.
• W3099103659 cites W2097382546 @default.
• W3099103659 cites W2107570993 @default.
• W3099103659 cites W2110432917 @default.
• W3099103659 cites W2118583982 @default.
• W3099103659 cites W2154543554 @default.
• W3099103659 cites W2156303855 @default.
• W3099103659 cites W2195327708 @default.
• W3099103659 cites W2248682259 @default.
• W3099103659 cites W2301614195 @default.
• W3099103659 cites W2312759843 @default.
• W3099103659 cites W2413680873 @default.
• W3099103659 cites W2570245225 @default.
• W3099103659 cites W2604170318 @default.
• W3099103659 cites W2723858288 @default.
• W3099103659 cites W2737793488 @default.
• W3099103659 cites W2741288947 @default.
• W3099103659 cites W2764142124 @default.
• W3099103659 cites W2765362864 @default.
• W3099103659 cites W2769156743 @default.
• W3099103659 cites W2785523944 @default.
• W3099103659 cites W2785770559 @default.
• W3099103659 cites W2790814646 @default.
• W3099103659 cites W2801078999 @default.
• W3099103659 cites W2802782337 @default.
• W3099103659 cites W2810674013 @default.
• W3099103659 cites W2887479338 @default.
• W3099103659 cites W2890406180 @default.
• W3099103659 cites W2892324548 @default.
• W3099103659 cites W2897371342 @default.
• W3099103659 cites W2906708625 @default.
• W3099103659 cites W2946072318 @default.
• W3099103659 cites W2981981976 @default.
• W3099103659 cites W2985081200 @default.
• W3099103659 cites W3011480675 @default.
• W3099103659 cites W3015712098 @default.
• W3099103659 cites W3022784012 @default.
• W3099103659 cites W3028395180 @default.
• W3099103659 cites W3033421341 @default.
• W3099103659 cites W3034118190 @default.
• W3099103659 cites W3036044758 @default.
• W3099103659 cites W4322696862 @default.
• W3099103659 doi "https://doi.org/10.1016/j.ynstr.2020.100267" @default.
• W3099103659 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7739170" @default.

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