Neuroscience
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Nerve damage leads to the development of disabling neuropathic pain in susceptible individuals, where patients present with pain as well as co-morbid behavioral changes, such as anhedonia, decreased motivation and depression. In this study we evaluated whether radial maze behavioral disruptions and glia-cytokine-neuronal adaptations in the hippocampus occurred in individual rats after nerve injury. Exploration behavior and spatial memory were quantified using a radial maze task, while mechanical allodynia was assessed using von Frey testing. ⋯ The withdrawal from pellet-seeking was found to be concomitant with distinct glial-cytokine-neuronal adaptations within the contralateral ventral hippocampus, including; increased expression of IL-1β and MCP-1; astrocyte atrophy and decreased area in the dentate gyrus; reactive microglia and increased FosB/ΔFosB expression in the cornu ammonis subfield. Therefore, glial-cytokine-neuronal adaptations in the ventral hippocampus may mediate individual differences in radial maze behavior following CCI. Our data suggest that individual neuroimmune signatures play a significant role in divergent behavioral trajectories following nerve injury, toward functional recovery and coping, or the emergence of ongoing affective state disturbances.
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The encoding, consolidation and retrieval of memories is a multifaceted process that depends strongly on the optimal level of arousal but high levels of arousal may trigger anxiety, which negatively impacts the memory processing by the brain. We investigated the role of CRH neurons in the central amygdala (CeA) for their capacity to modulate both, the anxiety-like behavior and hippocampus-dependent memory. First, we activated the CRH neurons in CeA using cre-dependent AAV-DREADD in CRH-cre mice. ⋯ The behavioral and memory effects were accompanied by increased c-Fos expression in the LC region. Pretreatment with CRH1 receptor antagonist antalarmin hydrochloride blocked the effects that were observed after the activation of the CeA projections to LC. Our findings highlight the role of CeA CRH neuronal population not only as a generator of anxiety but also demonstrate their role in the control of hippocampus-dependent memory.
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Adolescence is a window of vulnerability to environmental factors such as chronic stress that can disrupt brain development and cause long-lasting behavioral dysfunction, as seen in disorders like depression, anxiety, and schizophrenia. There are also sex differences in the prevalence of these disorders across the lifespan. However, the mechanisms of how adolescent stress contributes to neuropsychiatric phenotypes are not well understood, nor are the mediating effects of sex. ⋯ PFC-dependent cognitive functioning was also impaired in adult males stressed in adolescence. Adolescent stress disrupted expression patterns of parvalbumin (PV) and perineuronal nets (PNNs) in the PFC, as well as NMDA receptor subunit composition, in a sex- and age-specific manner. The findings presented here contribute to understanding how adolescent stress may lead to neuropsychiatric disorders such as anxiety by disrupting the development of the PFC and emotional behaviors.
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Current evidence suggests that the epithelial Na+ channel (ENaC) in the brain plays a significant role in the development of hypertension. ENaC is present in vasopressin (VP) neurons in the hypothalamus, suggesting that ENaC in VP neurons is involved in the regulation of blood pressure. Our recent study demonstrated that high dietary salt intake caused an increase in the expression and activity of ENaC that were responsible for the more depolarized basal membrane potential in VP neurons. ⋯ Moreover, chromatin immunoprecipitation demonstrated that the aldosterone-MR complex directly interacts with the promoter region of the γENaC gene. However, the treatment with aldosterone did not cause subcellular translocation of ENaC toward the plasma membrane nor an increase in ENaC Na+-leak current. These results indicate that expression of γENaC in VP neurons is induced by aldosterone and corticosterone through their MR and GR, respectively; however, aldosterone or corticosterone alone is not sufficient enough to increase ENaC current when they are applied to hypothalamic slices in vitro.
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In the ascending auditory pathway, the central nucleus of the inferior colliculus (IC) receives and integrates excitatory and inhibitory inputs from many bilateral lower auditory nuclei, intrinsic projections within the IC, contralateral IC through the commissure of the IC and from the auditory cortex. All these presynaptic excitatory and inhibitory inputs dynamically shape and modulate the auditory response properties of individual IC neurons. For this reason, acoustic response properties vary among individual IC neurons due to different activity pattern of presynaptic inputs. ⋯ Additionally, 30-minute short-term ESDNLL alone produces variation in the best frequency (BF) and minimum threshold (MT) of modulated IC neurons. These varied response parameters recover in different manner and time course among individual modulated IC neurons. Possible pathways and neural mechanisms underlying these findings are discussed.