Prelimbic Input to Basolateral Amygdala Facilitates the Acquisition of Trace Cued Fear Memory Under Weak Training Conditions

The ability to predict the occurrence of an aversive outcome based on available cues requires associative learning and plastic changes in the amygdala. When the predictive cue and aversive shock outcome are separated in time as in trace fear conditioning, additional circuitry is needed, including the prelimbic (PL) area of the prefrontal cortex. We have previously shown that neuronal firing in the PL during the trace interval separating the cue and shock is required for trace cued fear memory formation, but whether this mnemonic signal is conveyed to the amygdala is unknown. Here we show in males that silencing PL activity during the trace interval reduces Arc protein in the basolateral amygdala (BLA) of trace-conditioned rats. Then, using pathway-specific optogenetic and chemogenetic silencing, we show a role for direct PL-BLA communication in trace cued fear learning under weak training conditions, but not standard training. These results suggest that PL input to the BLA may serve to promote cued learning when the cue-shock relationship is most ambiguous and that other trace fear circuitry can compensate for the loss of this connection with additional training. This also highlights the challenge to studying how emotional memories are formed and stored within a distributed network and suggests that the function of individual connections within such a network may best be determined using weak training conditions

Aversive Stimuli Drive Drug Seeking in a State of Low Dopamine Tone

Background Stressors negatively impact emotional state and drive drug seeking, in part, by modulating the activity of the mesolimbic dopamine system. Unfortunately, the rapid regulation of dopamine signaling by the aversive stimuli that cause drug seeking is not well characterized. In a series of experiments, we scrutinized the subsecond regulation of dopamine signaling by the aversive stimulus, quinine, and tested its ability to cause cocaine seeking. Additionally, we examined the midbrain regulation of both dopamine signaling and cocaine seeking by the stress-sensitive peptide, corticotropin releasing factor (CRF). Methods Combining fast-scan cyclic voltammetry with behavioral pharmacology, we examined the effect of intraoral quinine administration on nucleus accumbens dopamine signaling and hedonic expression in 21 male Sprague-Dawley rats. We tested the role of CRF in modulating aversion-induced changes in dopamine concentration and cocaine seeking by bilaterally infusing the CRF antagonist, CP-376395, into the ventral tegmental area (VTA). Results We found that quinine rapidly reduced dopamine signaling on two distinct time scales. We determined that CRF acted in the VTA to mediate this reduction on only one of these time scales. Further, we found that the reduction of dopamine tone and quinine-induced cocaine seeking were eliminated by blocking the actions of CRF in the VTA during the experience of the aversive stimulus. Conclusions These data demonstrate that stress-induced drug seeking can occur in a terminal environment of low dopamine tone that is dependent on a CRF-induced decrease in midbrain dopamine activity

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Signaling in The Prefrontal Cortex Modulates Cued Fear Learning, But Not Spatial Working Memory, in Female Rats

A genetic polymorphism within the gene encoding the pituitary adenylate cyclase- activating polypeptide (PACAP) receptor type I (PAC1R) has recently been associated with hyper-reactivity to threat-related cues in women, but not men, with post-traumatic stress disorder (PTSD). PACAP is a highly conserved peptide, whose role in mediating adaptive physiological stress responses is well established. Far less is understood about the contribution of PACAP signaling in emotional learning and memory, particularly the encoding of fear to discrete cues. Moreover, a neurobiological substrate that may account for the observed link between PAC1R and PTSD in women, but not men, has yet to be identified. Sex differences in PACAP signaling during emotional learning could provide novel targets for the treatment of PTSD. Here we investigated the contribution of PAC1R signaling within the prefrontal cortex to the acquisition of cued fear in female and male rats. We used a variant of fear conditioning called trace fear conditioning, which requires sustained attention to fear cues and depends on working-memory like neuronal activity within the prefrontal cortex. We found that cued fear learning, but not spatial working memory, was impaired by administration of a PAC1R antagonist directly into the prelimbic area of the prefrontal cortex. This effect was specific to females. We also found that levels of mRNA for the PAC1R receptor in the prelimbic cortex were greater in females compared with males, and were highest during and immediately following the proestrus stage of the estrous cycle. Together, these results demonstrate a sex-specific role of PAC1R signaling in learning about threat-related cues

Elevated Trace Metal Content of Prokaryotic Communities Associated with Marine Oxygen Deficient Zones

Little is known about the trace metal content of marine prokaryotes, in part due to their co-occurrence with more abundant particulate phases in the upper ocean, such as phytoplankton and biogenic detritus, lithogenic minerals, and authigenic Mn and Fe oxyhydroxides. We attempt to isolate these biomass signals in particulate data from the US GEOTRACES Eastern Pacific Zonal Transect (cruise GP16) in the Eastern Tropical South Pacific (ETSP), which exhibited consistent maxima in P and other bioactive trace metals, and minima in particulate Mn, in the oxygen deficient zones (ODZs) of 13 stations. Nitrite maxima and nitrate deficits indicated the presence of denitrifying prokaryotic biomass within ETSP ODZs, and deep secondary fluorescence maxima at the upper ODZ boundaries of 10 stations also suggested the presence of low-light, autotrophic communities. ODZs were observed as far west as 99 degrees W, more than 2300 km from the South American coast, where eolian lithogenic and lateral/resuspended sedimentary inputs were negligible, presenting a unique opportunity to examine prokaryotic metal stoichiometries. ODZ particulate P maxima can rival gyre mixed layer biomass concentrations, are highly sensitive to oxygen, and are in excess of amounts scavengable by local Fe oxyhydroxides and acid-volatile sulfides. Even after correction for lithogenic and ferruginous-scavenged metals, ODZ P-maxima are often enriched in Cd, Co, Cu, Ni, V, and Zn, exhibiting particulate trace metal ratios to P that exceed mixed layer biomass ratios by factors of 2-9. ODZ prokaryotic communities may be largely hidden, TM-rich pools involved in the marine cycles of these bioactive trace metals

Genetic Disruption of System xc-Mediated Glutamate Release from Astrocytes Increases Negative-Outcome Behaviors While Preserving Basic Brain Function in Rat

The importance of neuronal glutamate to synaptic transmission throughout the brain illustrates the immense therapeutic potential and safety risks of targeting this system. Astrocytes also release glutamate, the clinical relevance of which is unknown as the range of brain functions reliant on signaling from these cells hasn\u27t been fully established. Here, we investigated system xc- (Sxc), which is a glutamate release mechanism with an in vivo rodent expression pattern that is restricted to astrocytes. As most animals do not express Sxc, we first compared the expression and sequence of the obligatory Sxc subunit xCT among major classes of vertebrate species. We found xCT to be ubiquitously expressed and under significant negative selective pressure. Hence, Sxc likely confers important advantages to vertebrate brain function that may promote biological fitness. Next, we assessed brain function in male genetically modified rats (MSxc) created to eliminate Sxc activity. Unlike other glutamatergic mechanisms, eliminating Sxc activity was not lethal and didn\u27t alter growth patterns, telemetry measures of basic health, locomotor activity, or behaviors reliant on simple learning. However, MSxc rats exhibited deficits in tasks used to assess cognitive behavioral control. In a pavlovian conditioned approach, MSxc rats approached a food-predicted cue more frequently than WT rats, even when this response was punished. In attentional set shifting, MSxc rats displayed cognitive inflexibility because of an increased frequency of perseverative errors. MSxc rats also displayed heightened cocaine-primed drug seeking. Hence, a loss of Sxc-activity appears to weaken control over nonreinforced or negative-outcome behaviors without altering basic brain function

Dissolved and particulate barium distributions along the US GEOTRACES North Atlantic and East Pacific zonal transects (GA03 and GP16): global implications for the marine barium cycle

Author Posting. © American Geophysical Union, 2022. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 36(6), (2022): e2022GB007330, https://doi.org/10.1029/2022gb007330.Processes controlling dissolved barium (dBa) were investigated along the GEOTRACES GA03 North Atlantic and GP16 Eastern Tropical Pacific transects, which traversed similar physical and biogeochemical provinces. Dissolved Ba concentrations are lowest in surface waters (∼35–50 nmol kg−1) and increase to 70–80 and 140–150 nmol kg−1 in deep waters of the Atlantic and Pacific transects, respectively. Using water mass mixing models, we estimate conservative mixing that accounts for most of dBa variability in both transects. To examine nonconservative processes, particulate excess Ba (pBaxs) formation and dissolution rates were tracked by normalizing particulate excess 230Th activities. Th-normalized pBaxs fluxes, with barite as the likely phase, have subsurface maxima in the top 1,000 m (∼100–200 μmol m−2 year−1 average) in both basins. Barite precipitation depletes dBa within oxygen minimum zones from concentrations predicted by water mass mixing, whereas inputs from continental margins, particle dissolution in the water column, and benthic diffusive flux raise dBa above predications. Average pBaxs burial efficiencies along GA03 and GP16 are ∼37% and 17%–100%, respectively, and do not seem to be predicated on barite saturation indices in the overlying water column. Using published values, we reevaluate the global freshwater dBa river input as 6.6 ± 3.9 Gmol year−1. Estuarine mixing processes may add another 3–13 Gmol year−1. Dissolved Ba inputs from broad shallow continental margins, previously unaccounted for in global marine summaries, are substantial (∼17 Gmol year−1), exceeding terrestrial freshwater inputs. Revising river and shelf dBa inputs may help bring the marine Ba isotope budget more into balance.The International GEOTRACES Programme is possible in part thanks to the support from the U.S. National Science Foundation (Grant OCE-1840868) to the Scientific Committee on Oceanic Research (SCOR). This research was supported by the National Science Foundation under Grant No. NSF OCE-0927951, NSF OCE-1137851, NSF OCE-1261214, and NSF OCE-1925503 to A. M. Shiller; NSF OCE-1829563 to R. F. Anderson; NSF OCE-0927064 and NSF OCE-1233688 to R. F. Anderson and M. Q. Fleisher; NSF OCE-0927754 to R. Lawrence Edwards; NSF OCE-1233903 to R. Lawrence Edwards and H. Cheng; NSF OCE-0926860 to L. F. Robinson; NSF OCE-0963026 and NSF OCE-1518110 to P. J. Lam; and NSF OCE-1232814 to B. S. Twining

Thresholds for adding degraded tropical forest to the conservation estate

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2, 3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked

Neurobiological Mechanisms That Contribute to Stress-related Cocaine Use

The ability of stressful life events to trigger drug use is particularly problematic for the management of cocaine addiction due to the unpredictable and often uncontrollable nature of stress. For this reason, understanding the neurobiological processes that contribute to stress-related drug use is important for the development of new and more effective treatment strategies aimed at minimizing the role of stress in the addiction cycle. In this review we discuss the neurocircuitry that has been implicated in stress-induced drug use with an emphasis on corticotropin releasing factor actions in the ventral tegmental area (VTA) and an important pathway from the bed nucleus of the stria terminalis to the VTA that is regulated by norepinephrine via actions at beta adrenergic receptors. In addition to the neurobiological mechanisms that underlie stress-induced cocaine seeking, we review findings suggesting that the ability of stressful stimuli to trigger cocaine use emerges and intensifies in an intake-dependent manner with repeated cocaine self-administration. Further, we discuss evidence that the drug-induced neuroadaptations that are necessary for heightened susceptibility to stress-induced drug use are reliant on elevated levels of glucocorticoid hormones at the time of cocaine use. Finally, the potential ability of stress to function as a “stage setter” for drug use – increasing sensitivity to cocaine and drug-associated cues – under conditions where it does not directly trigger cocaine seeking is discussed. As our understanding of the mechanisms through which stress promotes drug use advances, the hope is that so too will the available tools for effectively managing addiction, particularly in cocaine addicts whose drug use is stress-driven

Law in social work education: reviewing the evidence on teaching, learning and assessment

This paper presents the findings from a systemic review of knowledge relating to current practice in the teaching, learning and assessment of law in social work education. The research comprised an internationally conducted systematic review of the literature, together with a survey of current education practice in the four countries of the UK. Two consultation events sought the views of a range of stakeholders, including the perspectives of service users and carers. Set in the context of debates about the relationship between law and social work practice, this paper identifies the common themes emerging from the review and offers an analysis of key findings, together with priorities for future directions in education practice