Argo-Two Decades: Global Oceanography, Revolutionized.

Argo, an international, global observational array of nearly 4,000 autonomous robotic profiling floats, each measuring ocean temperature and salinity from 0 to 2,000 m on nominal 10-day cycles, has revolutionized physical oceanography. Argo started at the turn of the millennium,growing out of advances in float technology over the previous several decades. After two decades, with well over 2 million profiles made publicly available in real time, Argo data have underpinned more than 4,000 scientific publications and improved countless nowcasts, forecasts, and projections. We review a small subset of those accomplishments, such as elucidating remarkable zonal jets spanning the deep tropical Pacific; increasing understanding of ocean eddies and the roles of mixing in shaping water masses and circulation; illuminating interannual to decadal ocean variability; quantifying, in concert with satellite data, contributions of ocean warming and ice melting to sea level rise; improving coupled numerical weather predictions; and underpinning decadal climate forecasts.

PAC1 Receptor Internalization and Endosomal MEK/ERK Activation Is Essential for PACAP-Mediated Neuronal Excitability.

Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) activation of PAC1 receptors (Adcyap1r1) can significantly increase the excitability of diverse neurons through differential mechanisms. For guinea pig cardiac neurons, the modulation of excitability can be mediated in part by PAC1 receptor plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades. By contrast, PAC1 receptor-mediated excitability of hippocampal dentate gyrus granule cells appears independent of membrane-delimited AC/cAMP/PKA and PLC/PKC signaling. For both neuronal types, there is mechanistic convergence demonstrating that endosomal PAC1 receptor signaling has prominent roles. In these models, neuronal exposure to Pitstop2 to inhibit ß-arrestin/clathrin-mediated PAC1 receptor internalization eliminates PACAP modulation of excitability. ß-arrestin is a scaffold for a number of effectors especially MEK/ERK and notably, paradigms that inhibit PAC1 receptor endosome formation and ERK signaling also blunt the PACAP-induced increase in excitability. Detailed PAC1 receptor internalization and endosomal ERK signaling mechanisms have been confirmed in HEK PAC1R-EGFP cells and shown to be long lasting which appear to recapitulate the sustained electrophysiological responses. Thus, PAC1 receptor internalization/endosomal recruitment efficiently and efficaciously activates MEK/ERK signaling and appears to represent a singular and critical common denominator in regulating neuronal excitability by PACAP.

The Role of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Signaling in the Hippocampal Dentate Gyrus.

Pituitary adenylate cyclase-activating polypeptide (PACAP, ADCYAP1) dysregulation has been associated with multiple stress-related psychopathologies that may be related to altered hippocampal function. In coherence, PACAP- and PAC1 receptor (ADCYAP1R1)-null mice demonstrate changes in hippocampal-dependent behavioral responses, implicating the PACAPergic system function in this structure. Within the hippocampus, the dentate gyrus (DG) may play an important role in discerning the differences between similar contexts, and DG granule cells appear to both highly express PAC1 receptors and receive inputs from PACAP-expressing terminals. Here, we review the evidence from our laboratories and others that PACAP is an important regulator of activity within hippocampal circuits, particularly within the DG. These data are consistent with an increasing literature implicating PACAP circuits in stress-related pathologies such as post-traumatic stress disorder (PTSD) and implicate the hippocampus, and in particular the DG, as a critical site in which PACAP dysregulation can alter stress-related behaviors.

Pituitary adenylate cyclase-activating polypeptide-induced PAC1 receptor internalization and recruitment of MEK/ERK signaling enhance excitability of dentate gyrus granule cells.

Pituitary adenylate cyclase activating polypeptide (PACAP; ADCYAP1) is a pleiotropic neuropeptide widely distributed in both the peripheral and central nervous systems. PACAP and its specific cognate PAC1 receptor (ADCYAP1R1) play critical roles in the homeostatic maintenance of multiple physiological and behavioral systems. Notably, maladaptations in the PACAPergic system have been associated with several psychopathologies related to fear and anxiety. PAC1 receptor transcripts are highly expressed in granule cells of the dentate gyrus (DG). Here, we examined the direct effects of PACAP on DG granule cells in brain slices using whole cell patch recordings in current clamp mode. PACAP significantly increased the intrinsic excitability of DG granule cells via PAC1 receptor activation. This increased excitability was not mediated by adenylyl cyclase/cAMP or phospholipase C/PKC activation, but instead via activation of an extracellular signal-regulated kinase (ERK) signaling pathway initiated through PAC1 receptor endocytosis/endosomal signaling. PACAP failed to increase excitability in DG granule cells pretreated with the persistent sodium current blocker riluzole, suggesting that the observed PACAP effects required this component of the inward sodium current.

Chemogenetic Silencing of Prelimbic Cortex to Anterior Dorsomedial Striatum Projection Attenuates Operant Responding.

Operant (instrumental) conditioning is a laboratory analog for voluntary behavior and involves learning to make a response for a reinforcing outcome. The prelimbic cortex (PL), a region of the rodent medial prefrontal cortex, and the dorsomedial striatum (DMS), have been separately established as important in the acquisition of minimally-trained operant behavior. Despite dense anatomical connections between the two regions, experimenters have only recently linked projections from the PL to the posterior DMS (pDMS) in the acquisition of an operant response. Yet, it is still unknown if these projections mediate behavioral expression, and if more anterior regions of the DMS (aDMS), which receive dense projections from the PL, are also involved. Therefore, we utilized designer receptors exclusively activated by designer drugs (DREADDs) to test whether or not projections from the PL to the aDMS influence the expression of operant behavior. Rats underwent bilateral PL-targeted infusions of either a DREADD virus (AAV8-hSyn-hM4D(Gi)-mCherry) or a control virus (AAV8-hSyn-GFP). In addition, guide cannulae were implanted bilaterally in the aDMS. Rats were tested with both clozapine-N-oxide (CNO) (DREADD ligand) and vehicle infusions into the aDMS. Animals that had received the DREADD virus, but not the control virus, showed attenuated responding when they received CNO microinfusions into the aDMS, compared to vehicle infusions. Patch clamp electrophysiology verified the inhibitory effect of CNO on DREADDs-expressing PL neurons in acute brain slices. GFP-expressing control PL neurons were unaffected by CNO. The results add to the recent literature suggesting that connections between the PL and aDMS are important for the expression of minimally-trained operant responding.

Parallel signaling pathways of pituitary adenylate cyclase activating polypeptide (PACAP) regulate several intrinsic ion channels.

Pituitary adenylate cyclase activating polypeptide (PACAP), acting through its cognate receptors PAC1, VPAC1, and VPAC2, is a pleiotropic signaling neuropeptide of the vasoactive intestinal peptide/secretin/glucagon family. PACAP has known functions in neuronal growth, development, and repair, and central PACAP signaling has acute behavioral consequences. One of the ways in which PACAP may affect neuronal function is through the modulation of intrinsic membrane currents to control neuronal excitability. Here, we review the evidence of PACAP-dependent modulation of calcium- and voltage-gated potassium currents, hyperpolarization-activated cation currents, calcium currents, and voltage-gated sodium currents. Interestingly, PACAP signaling pathways diverge into parallel pathways to target different ionic currents for modulation, though single pathways are not limited to modulating just one target ionic current. Despite the various targets of modulation, the weight of the evidence suggests that PACAP signaling most commonly leads to a net increase in neuronal excitability. We discuss possible mechanisms by which PACAP signaling leads to the modulation of intrinsic membrane currents that may contribute to changes in behavior.

Robust warming of the global upper ocean.

A large ( approximately 10(23) J) multi-decadal globally averaged warming signal in the upper 300 m of the world's oceans was reported roughly a decade ago and is attributed to warming associated with anthropogenic greenhouse gases. The majority of the Earth's total energy uptake during recent decades has occurred in the upper ocean, but the underlying uncertainties in ocean warming are unclear, limiting our ability to assess closure of sea-level budgets, the global radiation imbalance and climate models. For example, several teams have recently produced different multi-year estimates of the annually averaged global integral of upper-ocean heat content anomalies (hereafter OHCA curves) or, equivalently, the thermosteric sea-level rise. Patterns of interannual variability, in particular, differ among methods. Here we examine several sources of uncertainty that contribute to differences among OHCA curves from 1993 to 2008, focusing on the difficulties of correcting biases in expendable bathythermograph (XBT) data. XBT data constitute the majority of the in situ measurements of upper-ocean heat content from 1967 to 2002, and we find that the uncertainty due to choice of XBT bias correction dominates among-method variability in OHCA curves during our 1993-2008 study period. Accounting for multiple sources of uncertainty, a composite of several OHCA curves using different XBT bias corrections still yields a statistically significant linear warming trend for 1993-2008 of 0.64 W m(-2) (calculated for the Earth's entire surface area), with a 90-per-cent confidence interval of 0.53-0.75 W m(-2).

Expanding oxygen-minimum zones in the tropical oceans.

Oxygen-poor waters occupy large volumes of the intermediate-depth eastern tropical oceans. Oxygen-poor conditions have far-reaching impacts on ecosystems because important mobile macroorganisms avoid or cannot survive in hypoxic zones. Climate models predict declines in oceanic dissolved oxygen produced by global warming. We constructed 50-year time series of dissolved-oxygen concentration for select tropical oceanic regions by augmenting a historical database with recent measurements. These time series reveal vertical expansion of the intermediate-depth low-oxygen zones in the eastern tropical Atlantic and the equatorial Pacific during the past 50 years. The oxygen decrease in the 300- to 700-m layer is 0.09 to 0.34 micromoles per kilogram per year. Reduced oxygen levels may have dramatic consequences for ecosystems and coastal economies.