Tonic activity in lateral habenula neurons acts as a neutral valence brake on reward-seeking behavior.

Survival requires both the ability to persistently pursue goals and the ability to determine when it is time to stop, an adaptive balance of perseverance and disengagement. Neural activity in the lateral habenula (LHb) has been linked to negative valence, but its role in regulating the balance between engaged reward seeking and disengaged behavioral states remains unclear. Here, we show that LHb neural activity is tonically elevated during minutes-long periods of disengagement from reward-seeking behavior, both when due to repeated reward omission (negative valence) and when sufficient reward has been consumed (positive valence). Furthermore, we show that LHb inhibition extends ongoing reward-seeking behavioral states but does not prompt task re-engagement. We find no evidence for similar tonic activity changes in ventral tegmental area dopamine neurons. Our findings support a framework in which tonic activity in LHb neurons suppresses engagement in reward-seeking behavior in response to both negatively and positively valenced factors.

Isotopic Characterization of Sulfate in a Shallow Aquifer Impacted by Agricultural Fertilizer.

The stable isotope ratios of groundwater sulfate (34 S/32 S, 18 O/16 O) are often used as tracers to help determine the origin of groundwater or groundwater contaminants. In agricultural watersheds, little is known about how the increased use of sulfur as a soil amendment to optimize crop production is affecting the isotopic composition of groundwater sulfate, especially in shallow aquifers. We investigated the isotopic composition of synthetic agricultural fertilizers and groundwater sulfate in an area of intensive agricultural activity, in Ontario, Canada. Groundwater samples from an unconfined surficial sand aquifer (Lake Algonquin Sand Aquifer) were analyzed from multi-level monitoring wells, riverbank seeps, and private domestic wells. Fertilizers used in the area were analyzed for sulfur/sulfate content and stable isotopic composition (δ18 O and/or δ34 S). Fertilizers were isotopically distinct from geological sources of groundwater sulfate in the watershed and groundwater sulfate exhibited a wide range of δ34 S (-6.9 to +20.0‰) and δ18 O (-5.0 to +13.7‰) values. Quantitative apportionment of sulfate sources based on stable isotope data alone was not possible, largely because two of the potential fertilizer sulfate sources had an isotopic composition on the mixing line between two natural geological sources of sulfate in the aquifer. This study demonstrates that, when sulfate isotope analysis is being used as a tracer or co-tracer of the origin of groundwater or of contaminants in groundwater, sulfate derived from synthetic fertilizer needs to be considered as a potential source, especially when other parameters such as nitrate independently indicate fertilizer impacts to groundwater quality.

Depression: the search for separable behaviors and circuits.

Major depressive disorder can manifest as different combinations of symptoms, ranging from a profound and incapacitating sadness, to a loss of interest in daily life, to an inability to engage in effortful, goal-directed behavior. Recent research has focused on defining the neural circuits that mediate separable features of depression in patients and preclinical animal models, and connections between frontal cortex and brainstem neuromodulators have emerged as candidate targets. The development of methods permitting recording and manipulation of neural circuits defined by connectivity has enabled the investigation of prefrontal-neuromodulatory circuit dynamics in animal models of depression with exquisite precision, a systems-level approach that has brought new insights by integrating these fields of depression research.

Glyphosate residues in rural groundwater, Nottawasaga River Watershed, Ontario, Canada.

BACKGROUND: The objective of this study was to investigate the occurrence of glyphosate residues (glyphosate and its metabolite AMPA) in shallow groundwater in a catchment dominated by agriculture, and to examine the potential for this groundwater to store and transmit these compounds to surface waters. RESULTS: Glyphosate residues were found in some of the groundwater samples collected in riparian (surface seeps), upland (mostly <20 m below ground) and wetland settings (<3 m below ground). Overall, glyphosate and AMPA were detected in 10.5 and 5.0%, respectively, of the groundwater samples analyzed as part of this study. All concentrations of glyphosate were well below Canadian guidelines for drinking water quality and for protection of aquatic life. Seasonal differences in concentrations in riparian seeps were possibly related to cycles of weather, herbicide application and degradation of glyphosate. Highest concentrations were at upland sites (663 ng L(-1) of glyphosate, 698 ng L(-1) of AMPA), apparently related to localized applications. Most glyphosate detections in wetlands were >0.5 km distant from possible areas of application, and, combined with other factors, suggest an atmospheric transport and deposition delivery mechanism. In both upland and wetland settings, highest glyphosate concentrations were sometimes not at the shallowest depths, indicating influence of hydrological factors. CONCLUSION: The glyphosate/AMPA detections in riparian seeps demonstrated that these compounds are persistent enough to allow groundwater to store and transmit glyphosate residues to surface waters. Detections in the wetlands support earlier evidence that atmospheric transport and deposition may lead to glyphosate contamination of environments not intended as targets of applications. This interpretation is further supported by detections of both glyphosate and AMPA in precipitation samples collected in the same watershed. © 2016 Her Majesty the Queen in Right of Canada Pest Management Science © 2016 Society of Chemical Industry.

Making Sense of Optogenetics.

This review, one of a series of articles, tries to make sense of optogenetics, a recently developed technology that can be used to control the activity of genetically-defined neurons with light. Cells are first genetically engineered to express a light-sensitive opsin, which is typically an ion channel, pump, or G protein-coupled receptor. When engineered cells are then illuminated with light of the correct frequency, opsin-bound retinal undergoes a conformational change that leads to channel opening or pump activation, cell depolarization or hyperpolarization, and neural activation or silencing. Since the advent of optogenetics, many different opsin variants have been discovered or engineered, and it is now possible to stimulate or inhibit neuronal activity or intracellular signaling pathways on fast or slow timescales with a variety of different wavelengths of light. Optogenetics has been successfully employed to enhance our understanding of the neural circuit dysfunction underlying mood disorders, addiction, and Parkinson's disease, and has enabled us to achieve a better understanding of the neural circuits mediating normal behavior. It has revolutionized the field of neuroscience, and has enabled a new generation of experiments that probe the causal roles of specific neural circuit components.

Effects of juvenile exposure to predator odor on adolescent and adult anxiety and pain nociception.

Clinical researchers have tracked patients with early life trauma and noted generalized anxiety disorder, unipolar depression, and risk-taking behaviors developing in late adolescence and into early adulthood. Animal models provide an opportunity to investigate the neural and developmental processes that underlie the relationship between early stress and later abnormal behavior. The present model used repeated exposure to 2,3,5-trimethyl-3-thiazoline (TMT), a component of fox feces, as an unconditioned fear-eliciting stimulus in order to induce stress in juvenile rats aged postnatal day (PND) 23 through 27. After further physical maturation characteristic of the adolescent stage (PND 42), animals were tested using an elevated plus maze (EPM) for anxiety and plantar test (Hargreaves method) for pain to assess any lingering effects of the juvenile stress. To assess how an additional stress later in life affects anxiety and pain nociception, PND 43 rats were exposed to inescapable shock (0.8mA) and again tested on EPM and plantar test. A final testing period was conducted in the adult (PND 63) rats to assess resulting changes in adult behaviors. TMT-exposed rats were significantly more anxious in adolescence than controls, but this difference disappeared after exposure to the secondary stressor. In adulthood, but not in adolescence, TMT-exposed rats demonstrated lower pain sensitivity than controls. These results suggest that early life stress can play a significant role in later anxiety and pain nociception, and offer insight into the development and manifestation of anxiety- and trauma-related disorders.

A discriminated conditioned punishment model of phobia.

Traditionally, the signaled avoidance (SA) paradigm has been used in an attempt to better understand human phobia. Animal models of this type have been criticized for ineffectively representing phobia. The SA model characterizes phobia as an avoidance behavior by presenting environmental cues, which act as warning signals to an aversive stimulus (ie, shock). Discriminated conditioned punishment (DCP) is an alternative paradigm that characterizes phobia as a choice behavior in which fear serves to punish an otherwise adaptive behavior. The present study quantifies the differences between the paradigms and suggests that DCP offers an alternative paradigm for phobia. Rats trained on either SA or DCP were compared on a number of behavioral variables relevant to human phobia. Results indicate that rats in the DCP paradigm responded significantly earlier to warning signals and were more effective at preventing shocks than rats in the SA paradigm. Implications of this alternative paradigm are discussed.