Impacts of artificial light at night on the early life history of two ecosystem engineers.

Sessile marine invertebrates play a vital role as ecosystem engineers and in benthic-pelagic coupling. Most benthic fauna develop through larval stages and the importance of natural light cycles for larval biology and ecology is long-established. Natural light-dark cycles regulate two of the largest ocean-scale processes that are fundamental to larvae's life cycle: the timing of broadcast spawning for successful fertilization and diel vertical migration for foraging and predator avoidance. Given the reliance on light and the ecological role of larvae, surprisingly little is known about the impacts of artificial light at night (ALAN) on the early life history of habitat-forming species. We quantified ALAN impacts on larval performance (survival, growth, development) of two cosmopolitan ecosystem engineers in temperate marine ecosystems, the mussel Mytilus edulis and the barnacle Austrominius modestus. Higher ALAN irradiance reduced survival in both species (57% and 13%, respectively). ALAN effects on development and growth were small overall, and different between species, time-points and parentage. Our results show that ALAN adversely affects larval survival and reiterates the importance of paternal influence on offspring performance. ALAN impacts on the early life stages of ecosystem engineering species have implications not only for population viability but also the ecological communities that these species support. This article is part of the theme issue 'Light pollution in complex ecological systems'.

Cannabinoid regulation of neurons in the dentate gyrus during epileptogenesis: Role of CB1R-associated proteins and downstream pathways.

The hippocampal formation plays a central role in the development of temporal lobe epilepsy (TLE), a disease characterized by recurrent, unprovoked epileptic discharges. TLE is a neurologic disorder characterized by acute long-lasting seizures (i.e., abnormal electrical activity in the brain) or seizures that occur in close proximity without recovery, typically after a brain injury or status epilepticus. After status epilepticus, epileptogenic hyperexcitability develops gradually over the following months to years, resulting in the emergence of chronic, recurrent seizures. Acting as a filter or gate, the hippocampal dentate gyrus (DG) normally prevents excessive excitation from propagating through the hippocampus, and is considered a critical region in the progression of epileptogenesis in pathological conditions. Importantly, lipid-derived endogenous cannabinoids (endocannabinoids), which are produced on demand as retrograde messengers, are central regulators of neuronal activity in the DG circuit. In this review, we summarize recent findings concerning the role of the DG in controlling hyperexcitability and propose how DG regulation by cannabinoids (CBs) could provide avenues for therapeutic interventions. We also highlight possible pathways and manipulations that could be relevant for the control of hyperexcitation. The use of CB compounds to treat epilepsies is controversial, as anecdotal evidence is not always validated by clinical trials. Recent publications shed light on the importance of the DG as a region regulating incoming hippocampal excitability during epileptogenesis. We review recent findings concerning the modulation of the hippocampal DG circuitry by CBs and discuss putative underlying pathways. A better understanding of the mechanisms by which CBs exert their action during seizures may be useful to improve therapies.

Reorganization of CA1 dendritic dynamics by hippocampal sharp-wave ripples during learning.

The hippocampus plays a critical role in memory consolidation, mediated by coordinated network activity during sharp-wave ripple (SWR) events. Despite the link between SWRs and hippocampal plasticity, little is known about how network state affects information processing in dendrites, the primary sites of synaptic input integration and plasticity. Here, we monitored somatic and basal dendritic activity in CA1 pyramidal cells in behaving mice using longitudinal two-photon calcium imaging integrated with simultaneous local field potential recordings. We found immobility was associated with an increase in dendritic activity concentrated during SWRs. Coincident dendritic and somatic activity during SWRs predicted increased coupling during subsequent exploration of a novel environment. In contrast, somatic-dendritic coupling and SWR recruitment varied with cells' tuning distance to reward location during a goal-learning task. Our results connect SWRs with the stabilization of information processing within CA1 neurons and suggest that these mechanisms may be dynamically biased by behavioral demands.

Local feedback inhibition tightly controls rapid formation of hippocampal place fields.

Hippocampal place cells underlie spatial navigation and memory. Remarkably, CA1 pyramidal neurons can form new place fields within a single trial by undergoing rapid plasticity. However, local feedback circuits likely restrict the rapid recruitment of individual neurons into ensemble representations. This interaction between circuit dynamics and rapid feature coding remains unexplored. Here, we developed "all-optical" approaches combining novel optogenetic induction of rapidly forming place fields with 2-photon activity imaging during spatial navigation in mice. We find that induction efficacy depends strongly on the density of co-activated neurons. Place fields can be reliably induced in single cells, but induction fails during co-activation of larger subpopulations due to local circuit constraints imposed by recurrent inhibition. Temporary relief of local inhibition permits the simultaneous induction of place fields in larger ensembles. We demonstrate the behavioral implications of these dynamics, showing that our ensemble place field induction protocol can enhance subsequent spatial association learning.

Supramammillary regulation of locomotion and hippocampal activity.

Locomotor speed is a basic input used to calculate one's position, but where this signal comes from is unclear. We identified neurons in the supramammillary nucleus (SuM) of the rodent hypothalamus that were highly correlated with future locomotor speed and reliably drove locomotion when activated. Robust locomotion control was specifically identified in Tac1 (substance P)­expressing (SuMTac1+) neurons, the activation of which selectively controlled the activity of speed-modulated hippocampal neurons. By contrast, Tac1-deficient (SuMTac1−) cells weakly regulated locomotion but potently controlled the spike timing of hippocampal neurons and were sufficient to entrain local network oscillations. These findings emphasize that the SuM not only regulates basic locomotor activity but also selectively shapes hippocampal neural activity in a manner that may support spatial navigation.

Reactivation predicts the consolidation of unbiased long-term cognitive maps.

Spatial memories that can last a lifetime are thought to be encoded during 'online' periods of exploration and subsequently consolidated into stable cognitive maps through their 'offline' reactivation. However, the mechanisms and computational principles by which offline reactivation stabilize long-lasting spatial representations remain poorly understood. Here, we employed simultaneous fast calcium imaging and electrophysiology to track hippocampal place cells over 2 weeks of online spatial reward learning behavior and offline resting. We describe that recruitment to persistent network-level offline reactivation of spatial experiences in mice predicts the future representational stability of place cells days in advance of their online reinstatement. Moreover, while representations of reward-adjacent locations are generally more stable across days, offline-reactivation-related stability is, conversely, most prominent for reward-distal locations. Thus, while occurring on the tens of milliseconds timescale, offline reactivation is uniquely associated with the stability of multiday representations that counterbalance the overall reward-adjacency bias, thereby predicting the stabilization of cognitive maps that comprehensively reflect entire underlying spatial contexts. These findings suggest that post-learning offline-related memory consolidation plays a complimentary and computationally distinct role in learning compared to online encoding.

Maximally selective single-cell target for circuit control in epilepsy models.

Neurological and psychiatric disorders are associated with pathological neural dynamics. The fundamental connectivity patterns of cell-cell communication networks that enable pathological dynamics to emerge remain unknown. Here, we studied epileptic circuits using a newly developed computational pipeline that leveraged single-cell calcium imaging of larval zebrafish and chronically epileptic mice, biologically constrained effective connectivity modeling, and higher-order motif-focused network analysis. We uncovered a novel functional cell type that preferentially emerged in the preseizure state, the superhub, that was unusually richly connected to the rest of the network through feedforward motifs, critically enhancing downstream excitation. Perturbation simulations indicated that disconnecting superhubs was significantly more effective in stabilizing epileptic circuits than disconnecting hub cells that were defined traditionally by connection count. In the dentate gyrus of chronically epileptic mice, superhubs were predominately modeled adult-born granule cells. Collectively, these results predict a new maximally selective and minimally invasive cellular target for seizure control.

Alternating sources of perisomatic inhibition during behavior.

Interneurons expressing cholecystokinin (CCK) and parvalbumin (PV) constitute two key GABAergic controllers of hippocampal pyramidal cell output. Although the temporally precise and millisecond-scale inhibitory regulation of neuronal ensembles delivered by PV interneurons is well established, the in vivo recruitment patterns of CCK-expressing basket cell (BC) populations has remained unknown. We show in the CA1 of the mouse hippocampus that the activity of CCK BCs inversely scales with both PV and pyramidal cell activity at the behaviorally relevant timescales of seconds. Intervention experiments indicated that the inverse coupling of CCK and PV GABAergic systems arises through a mechanism involving powerful inhibitory control of CCK BCs by PV cells. The tightly coupled complementarity of two key microcircuit regulatory modules demonstrates a novel form of brain-state-specific segregation of inhibition during spontaneous behavior.

The effect of previous treatment with bisphosphonate and renal impairment on the response to denosumab in osteoporosis: a 'real-life' study.

PURPOSE: To investigate changes in bone mineral density (BMD) following denosumab after previous bisphosphonate therapy and the impact of chronic kidney disease (CKD) on response. METHODS: A retrospective study of 134 patients (11 M, 123 F) aged [mean (SD)] 72 [11] years on denosumab was undertaken. Ninety-five patients had previously been on oral and 28 on iv bisphosphonate. Lumbar spine (LS), total hip (TH) and femoral neck (FN) BMD were measured before treatment and at 2.7 [1.2] years. GFR was < 35 ml/min in 24 patients (18%). Ninety-four (18 M, 76 F) patients aged 71 [11] years transitioning to zoledronate were also studied. RESULTS: BMD improved following denosumab [mean (SEM) % change LS: 6.0 (0.62) p < 0.001, TH: 2.28 (0.64) p < 0.001, FN: 1.9 (0.77) p = 0.045]. Changes at the TH and FN were lower in patients with GFR < 35 ml/min (Group B) compared to those with GFR > 35 ml/min (Group A) [% change TH; Group A: 2.9 (0.72), Group B: - 0.84 (1.28), p = 0.015, FN; Group A: 2.76 (0.86), Group B: - 1.47 (1.53), p = 0.025]. % change in BMD at the FN and PTH were negatively associated (r = - 0.25, p = 0.013). BMD changes were not different at 12-18 months between patients on denosumab compared to zoledronate [% change at LS: denosumab: 3.97% (0.85), zoledronate: 2.6% (0.5), p = 0.19 TH: denosumab: 0.97% (0.58), zoledronate: 0.92% (0.6), p = 0.95). CONCLUSION: Denosumab increases BMD following previous bisphosphonate treatment and is comparable to zoledronate. Lower response seen at the hip in CKD is related to PTH concentrations.

Volumetric Ca2+ Imaging in the Mouse Brain Using Hybrid Multiplexed Sculpted Light Microscopy.

Calcium imaging using two-photon scanning microscopy has become an essential tool in neuroscience. However, in its typical implementation, the tradeoffs between fields of view, acquisition speeds, and depth restrictions in scattering brain tissue pose severe limitations. Here, using an integrated systems-wide optimization approach combined with multiple technical innovations, we introduce a new design paradigm for optical microscopy based on maximizing biological information while maintaining the fidelity of obtained neuron signals. Our modular design utilizes hybrid multi-photon acquisition and allows volumetric recording of neuroactivity at single-cell resolution within up to 1 × 1 × 1.22 mm volumes at up to 17 Hz in awake behaving mice. We establish the capabilities and potential of the different configurations of our imaging system at depth and across brain regions by applying it to in vivo recording of up to 12,000 neurons in mouse auditory cortex, posterior parietal cortex, and hippocampus.

Methicillin resistance in Staphylococcus aureus infections among patients colonized with methicillin-susceptible Staphylococcus aureus.

OBJECTIVES: We have noticed that patients colonized with methicillin-susceptible Staphylococcus aureus (MSSA) rarely get methicillin-resistant S. aureus (MRSA) infections. The purpose of this study was to compare the odds of a Staphylococcus aureus (SA) infection being an MRSA infection in MSSA carriers, MRSA carriers and non-carriers of SA. METHODS: Hospitalizations of adult patients at the Cleveland Clinic Health System from 2008 to 2015 were screened to identify those where the patient was tested for SA colonization. The first such hospitalization was identified. Among these 90 891 patients, those who had an SA infection during the hospitalization were included. SA carrier status (MRSA, MSSA, or non-carrier), was defined based on the first nasal SA test result. The association of carrier status and MRSA infection was examined. RESULTS: The mean (±standard deviation (SD)) age of the 1999 included patients was 61 (17) years, and 1160 (58%) were male. Thirty percent, 26%, and 44%, were MRSA carriers, MSSA carriers and non-carriers, respectively. Of the 601 SA infections in MRSA carriers (reference group), 552 (92%) were MRSA infections compared with 42 (8%) of 516 in MSSA carriers (odds ratio (OR) 0.008, 95% confidence interval (CI) 0.005-0.012, p <0.0001) and 430 (49%) of 882 in non-carriers (OR 0.072, 95% CI 0.051-0.100, p <0.0001), after controlling for age, sex, hospital length of stay and calendar year. CONCLUSION: Among patients with SA infection, the odds of the infection being an MRSA infection are 125-times lower in an MSSA carrier than in an MRSA carrier.

Control of recollection by slow gamma dominating mid-frequency gamma in hippocampus CA1.

Behavior is used to assess memory and cognitive deficits in animals like Fmr1-null mice that model Fragile X Syndrome, but behavior is a proxy for unknown neural events that define cognitive variables like recollection. We identified an electrophysiological signature of recollection in mouse dorsal Cornu Ammonis 1 (CA1) hippocampus. During a shocked-place avoidance task, slow gamma (SG) (30-50 Hz) dominates mid-frequency gamma (MG) (70-90 Hz) oscillations 2-3 s before successful avoidance, but not failures. Wild-type (WT) but not Fmr1-null mice rapidly adapt to relocating the shock; concurrently, SG/MG maxima (SGdom) decrease in WT but not in cognitively inflexible Fmr1-null mice. During SGdom, putative pyramidal cell ensembles represent distant locations; during place avoidance, these are avoided places. During shock relocation, WT ensembles represent distant locations near the currently correct shock zone, but Fmr1-null ensembles represent the formerly correct zone. These findings indicate that recollection occurs when CA1 SG dominates MG and that accurate recollection of inappropriate memories explains Fmr1-null cognitive inflexibility.

Impaired hippocampal place cell dynamics in a mouse model of the 22q11.2 deletion.

Hippocampal place cells represent the cellular substrate of episodic memory. Place cell ensembles reorganize to support learning but must also maintain stable representations to facilitate memory recall. Despite extensive research, the learning-related role of place cell dynamics in health and disease remains elusive. Using chronic two-photon Ca2+ imaging in hippocampal area CA1 of wild-type and Df(16)A+/- mice, an animal model of 22q11.2 deletion syndrome, one of the most common genetic risk factors for cognitive dysfunction and schizophrenia, we found that goal-oriented learning in wild-type mice was supported by stable spatial maps and robust remapping of place fields toward the goal location. Df(16)A+/- mice showed a significant learning deficit accompanied by reduced spatial map stability and the absence of goal-directed place cell reorganization. These results expand our understanding of the hippocampal ensemble dynamics supporting cognitive flexibility and demonstrate their importance in a model of 22q11.2-associated cognitive dysfunction.

Active place avoidance is no more stressful than unreinforced exploration of a familiar environment.

Training in the active place avoidance task changes hippocampus synaptic function, the dynamics of hippocampus local field potentials, place cell discharge, and active place avoidance memory is maintained by persistent PKMζ activity. The extent to which these changes reflect memory processes and/or stress responses is unknown. We designed a study to assess stress within the active place avoidance task by measuring serum corticosterone (CORT) at different stages of training. CORT levels did not differ between trained mice that learned to avoid the location of the mild foot shock, and untrained no-shock controls exposed to the same environment for the same amount of time. Yoked mice, that received unavoidable shocks in the same time sequence as the trained mice, had significantly higher CORT levels than mice in the trained and no-shock groups after the first trial. This increase in CORT disappeared by the fourth trial the following day, and levels of CORT for all groups matched that of home cage controls. The data demonstrate that place avoidance training is no more stressful than experiencing a familiar environment. We conclude that changes in neural function as a result of active place avoidance training are likely to reflect learning and memory processes rather than stress. © 2016 Wiley Periodicals, Inc.

The prevalence of vertebral deformities is increased with higher egg incubation temperatures and triploidy in Atlantic salmon Salmo salar L.

Suboptimal egg incubation temperature is a risk factor for the development of skeletal deformities in teleosts. Triplicate diploid and triploid Atlantic salmon, Salmo salar L., egg batches were incubated at 6, 8 and 10 °C up until first feeding, whereupon fish were reared on a natural temperature before examination for externally visible skeletal deformities (jaw and spine) and radiographed for vertebral deformities and morphology at the parr stage. Increasing incubation temperatures and triploidy increased the number of fish showing one or more deformed vertebrae. Triploids had significantly higher mean vertebrae cranio-caudal length (L) and dorsal-ventral height (H) ratio at 6 and 10 °C than diploids, but triploidy had no effect on mean vertebrae centra area. Triploids demonstrated an increase in lower jaw deformities with increased incubation temperature, whereas jaw deformities were rare in diploids. Fish incubated at 10 °C had a significantly lower mean vertebral number than fish incubated at 6 °C, and triploids had lower mean vertebral numbers than diploids. Diploid fish with 58 vertebrae had a significantly higher mean vertebral centra area than fish with 59 vertebrae, but vertebral number did not affect the mean vertebral L/H ratio. The results are discussed with respect to the welfare and production of farmed salmonids.

Hippocampal CA2 activity patterns change over time to a larger extent than between spatial contexts.

The hippocampal CA2 subregion has a different anatomical connectivity pattern within the entorhino-hippocampal circuit than either the CA1 or CA3 subregion. Yet major differences in the neuronal activity patterns of CA2 compared with the other CA subregions have not been reported. We show that standard spatial and temporal firing patterns of individual hippocampal principal neurons in behaving rats, such as place fields, theta modulation, and phase precession, are also present in CA2, but that the CA2 subregion differs substantially from the other CA subregions in its population coding. CA2 ensembles do not show a persistent code for space or for differences in context. Rather, CA2 activity patterns become progressively dissimilar over time periods of hours to days. The weak coding for a particular context is consistent with recent behavioral evidence that CA2 circuits preferentially support social, emotional, and temporal rather than spatial aspects of memory.

Vaccination and triploidy increase relative heart weight in farmed Atlantic salmon, Salmo salar L.

Heart morphology is particularly plastic in teleosts and differs between farmed and wild Atlantic salmon. However, little is known about how different culture practices and sex affect heart morphology. This study investigated how vaccination, triploidy and sex affected heart size and heart morphology (ventricle shape, angle of the bulbus arteriosus) in farmed Atlantic salmon for 18 months following vaccination (from c. 50-3000 g body weight). In addition, hearts were examined histologically after 7 months in sea water. All fish sampled were sexually immature. Vaccinated fish had significantly heavier hearts relative to body weight and a more triangular ventricle than unvaccinated fish, suggesting a greater cardiac workload. Irrespective of time, triploids had significantly heavier hearts relative to body weight, a more acute angle of the bulbus arteriosus and less fat deposition in the epicardium than diploids. The ventricle was also more triangular in triploids than diploids at seawater transfer. Sex had transient effects on the angle of the bulbus arteriosus, but no effect on relative heart weight or ventricle shape. From a morphological perspective, the results indicate that vaccination and triploidy increase cardiac workload in farmed Atlantic salmon.

Recent memory for socially transmitted food preferences in rats does not depend on the hippocampus.

The standard model of systems consolidation holds that the hippocampus (HPC) is involved only in the initial storage and retrieval of a memory. With time hippocampal-neocortical interactions slowly strengthen the neocortical memory, ultimately enabling retrieval of the memory without the HPC. Key support for this idea comes from experiments measuring memory recall in the socially-transmitted food preference (STFP) task in rats. HPC damage within a day or two of STFP learning can abolish recall, but similar damage five or more days after learning has no effect. We hypothesize that disruption of cellular consolidation outside the HPC could contribute to the amnesia with recent memories, perhaps playing a more important role than the loss of HPC. This view predicts that intraHPC infusion of Tetrodotoxin (TTX), which can block conduction of action potentials from the lesion sites, will block the retrograde amnesia in the STFP task. Here we confirm the previously reported retrograde amnesia with neurotoxic HPC damage within the first day after learning, but show that co-administration of TTX with the neurotoxin blocks the retrograde amnesia despite very extensive HPC damage. These results indicate that HPC damage disrupts cellular consolidation of the recent memory elsewhere; STFP memory may not ever depend on the HPC.

The effect of vaccination, ploidy and smolt production regime on pathological melanin depositions in muscle tissue of Atlantic salmon, Salmo salar L.

The presence of melanin in muscle fillets of farmed salmon represents a considerable quality problem for the salmon industry with major economic concerns. In this study, we have examined the presence of abnormal pigmentation in vaccinated versus unvaccinated Atlantic salmon, Salmo salar L., and evaluated possible differences between diploid and triploid fish. Furthermore, the impact of the smolt production regime at ambient (4.5 °C) versus elevated temperature (16 °C) was investigated. Pigmented muscle spots were analysed for the expression of genes involved in melanization (tyrosinase gene family) and immune-related response in addition to morphological investigations. The proportion of fish with intramuscular melanin deposits was not significantly different between vaccinated and unvaccinated fish, regardless of ploidy. However, an interaction between vaccination and smolt regime was shown, where smoltification at elevated temperature after vaccination increased the number of affected individuals compared with vaccination followed by simulated natural smoltification. Furthermore, there were overall more fish with melanin spots amongst the triploids compared with their diploid counterparts. Transcription of the tyrosinase gene family confirmed an onsite melanogenesis in all pigment spots. The histological examination and the expression of the immune-related genes revealed a chronic polyphasic myopathy that was not affected by vaccination, ploidy or smolt production regime.

The effect of ploidy and incubation temperature on survival and the prevalence of aplasia of the septum transversum in Atlantic salmon, Salmo salar L.

Heart deformities are a concern in aquaculture and are linked to egg incubation temperature. Diploid and triploid Atlantic salmon, Salmo salar L., were incubated at 6, 8 and 10 °C and analysed for aplasia of the septum transversum (n = 150 ploidy⁻¹ incubation temperature⁻¹). Heart morphology (size and shape) was assessed in fish incubated at 6 °C and in fish with and without aplasia of the septum transversum (n = 9 group⁻¹) incubated at 10 °C. Egg mortality was significantly higher in triploids than in diploids at all incubation temperatures, and increased egg incubation temperatures increased mortality in both ploidy. Triploids grew quicker than diploids after egg incubation at 10 °C, but not at 6 °C. Aplasia of the septum transversum occurred only in triploid fish after incubation at 6 °C and 8 °C (0.7% and 3.3%, respectively) and was significantly greater (P ≤ 0.05) in triploids after incubation at 10 °C compared with diploids (30% and 18%, respectively). Aplasia of the septum transversum significantly increased heart mass and resulted in a long flat ventricle compared with fish displaying a septum transversum. The results suggest triploid salmon should be incubated below 8 °C.