Hippocampal lesions impair non-navigational spatial memory in macaques.

Decades of studies robustly support a critical role for the hippocampus in spatial memory across a wide range of species. Hippocampal damage produces clear and consistent deficits in allocentric spatial memory that requires navigating through space in rodents, non-human primates, and humans. By contrast, damage to the hippocampus spares performance in most non-navigational spatial memory tasks-which can typically be resolved using egocentric cues. We previously found that transient inactivation of the hippocampus impairs performance in the Hamilton Search Task (HST), a self-ordered non-navigational spatial search task. A key question, however, still needs to be addressed. Acute, reversible inactivation of the hippocampus may have resulted in an impairment in the HST because this approach does not allow for neuroplastic compensation, may prevent the development of an alternative learning strategy, and/or may produce network-based effects that disrupt performance. We compared learning and performance on the HST in male rhesus macaques (six unoperated control animals and six animals that underwent excitotoxic lesions of the hippocampus). We found a significant impairment in animals with hippocampal lesions. While control animals improved in performance over the course of 45 days of training, performance in animals with hippocampal lesions remained at chance levels. The HST thus represents a sensitive assay for probing the integrity of the hippocampus in non-human primates. These data provide evidence demonstrating that the hippocampus is critical for this type of non-navigational spatial memory, and help to reconcile the many null findings previously reported.

Climatic and biogeographic processes underlying the diversification of the pantropical flowering plant family Annonaceae.

Tropical forests harbor the richest biodiversity among terrestrial ecosystems, but few studies have addressed the underlying processes of species diversification in these ecosystems. We use the pantropical flowering plant family Annonaceae as a study system to investigate how climate and biogeographic events contribute to diversification. A super-matrix phylogeny comprising 835 taxa (34% of Annonaceae species) based on eight chloroplast regions was used in this study. We show that global temperature may better explain the recent rapid diversification in Annonaceae than time and constant models. Accelerated accumulation of niche divergence (around 15 Ma) lags behind the increase of diversification rate (around 25 Ma), reflecting a heterogeneous transition to recent diversity increases. Biogeographic events are related to only two of the five diversification rate shifts detected. Shifts in niche evolution nevertheless appear to be associated with increasingly seasonal environments. Our results do not support the direct correlation of any particular climatic niche shifts or historical biogeographical event with shifts in diversification rate. Instead, we suggest that Annonaceae diversification can lead to later niche divergence as a result of increasing interspecific competition arising from species accumulation. Shifts in niche evolution appear to be associated with increasingly seasonal environments. Our results highlight the complexity of diversification in taxa with long evolutionary histories.

Neurons in the monkey frontopolar cortex encode learning stage and goal during a fast learning task.

The frontopolar cortex (FPC) is, to date, one of the least understood regions of the prefrontal cortex. The current understanding of its function suggests that it plays a role in the control of exploratory behaviors by coordinating the activities of other prefrontal cortex areas involved in decision-making and exploiting actions based on their outcomes. Based on this hypothesis, FPC would drive fast-learning processes through a valuation of the different alternatives. In our study, we used a modified version of a well-known paradigm, the object-in-place (OIP) task, to test this hypothesis in electrophysiology. This paradigm is designed to maximize learning, enabling monkeys to learn in one trial, which is an ability specifically impaired after a lesion of the FPC. We showed that FPC neurons presented an extremely specific pattern of activity by representing the learning stage, exploration versus exploitation, and the goal of the action. However, our results do not support the hypothesis that neurons in the frontal pole compute an evaluation of different alternatives. Indeed, the position of the chosen target was strongly encoded at its acquisition, but the position of the unchosen target was not. Once learned, this representation was also found at the problem presentation, suggesting a monitoring activity of the synthetic goal preceding its acquisition. Our results highlight important features of FPC neurons in fast-learning processes without confirming their role in the disengagement of cognitive control from the current goals.

Distinct roles of monkey OFC-subcortical pathways in adaptive behavior.

To be the most successful, primates must adapt to changing environments and optimize their behavior by making the most beneficial choices. At the core of adaptive behavior is the orbitofrontal cortex (OFC) of the brain, which updates choice value through direct experience or knowledge-based inference. Here, we identify distinct neural circuitry underlying these two separate abilities. We designed two behavioral tasks in which macaque monkeys updated the values of certain items, either by directly experiencing changes in stimulus-reward associations, or by inferring the value of unexperienced items based on the task's rules. Chemogenetic silencing of bilateral OFC combined with mathematical model-fitting analysis revealed that monkey OFC is involved in updating item value based on both experience and inference. In vivo imaging of chemogenetic receptors by positron emission tomography allowed us to map projections from the OFC to the rostromedial caudate nucleus (rmCD) and the medial part of the mediodorsal thalamus (MDm). Chemogenetic silencing of the OFC-rmCD pathway impaired experience-based value updating, while silencing the OFC-MDm pathway impaired inference-based value updating. Our results thus demonstrate a dissociable contribution of distinct OFC projections to different behavioral strategies, and provide new insights into the neural basis of value-based adaptive decision-making in primates.

Molecular ecology of highest priority critically important antibiotic resistant Escherichia coli from mammals housed at an urban zoo.

OBJECTIVES: Zoos are environments where species of highly valued animals are kept largely separated from others and the wider world. We report the molecular ecology of critically important antibiotic resistant (ABR) Escherichia coli carried by 28 mammalian species housed in a zoo located in an urban residential district. METHODS: Over 3 months we collected 167 faecal samples from captive mammals and processed for E. coli resistant to third-generation cephalosporins (3GC-R) and fluoroquinolones (FQ-R). Isolates were sequenced using Illumina. RESULTS: We identified high rates of faecal sample-level positivity, with 50%, 57% and 36% of mammalian species excreting 3GC-R, FQ-R or dual 3GC-R/FQ-R E. coli, respectively. Isolates represented multiple ST and ABR mechanisms; CTX-M-15 and CMY-2 dominated for 3GC-R, and target-site mutation caused 75% of FQ-R. We identified multiple examples of ABR E. coli transmission between mammalian species in separate enclosures, and a variant of the epidemic plasmid pCT within the zoo. There was no evidence for ABR E. coli leaving the zoo, based on comparative analysis with E. coli from humans, cattle and dogs isolated from the 50 × 50 km region in which the zoo is located. Amoxicillin/clavulanate was the most widely used antibiotic in the zoo, and we identified four widely disseminated amoxicillin/clavulanate resistance mechanisms, including a previously unreported inhibitor-resistant TEM, and the carbapenemase OXA-181. CONCLUSIONS: We conclude that the zoo studied here is a 'melting pot' for the selection and circulation of 3GC-R and FQ-R E. coli, but these circulating E. coli appear captive within the zoo.

How do fishes manage disease?

Disease drives the evolution of proactive and reactive mitigation behaviours in fishes as for terrestrial animals. Understanding fish self-remedy behaviours could discover algal bioactives, reveal novel strategies for disease management, identify new habitats or ecosystems critical to population health and conservation, and enhance knowledge of interspecific evolutionary relationships and communication.

Three new species of Mitrephora (Annonaceae) from Thailand.

Three new Mitrephora species (Annonaceae), M.langsuanensis sp. nov., M.sirindhorniae sp. nov. and M.sukhothaiensis sp. nov., are described from Thailand. Mitrephoralangsuanensis resembles M.macclurei, but its leaves have more secondary veins, and its flowers have more carpels, with yellow-and-pink striped outer petals with a margin that becomes undulate with age. Mitrephorasirindhorniae resembles M.tomentosa, but has larger sepals and petals, longer flowering pedicels, and shorter monocarp stipes, with monocarps that have a longitudinal ridge. Mitrephorasukhothaiensis is distinct from its Thai congeners in having outer petals that reflex at maturity and inner petals with a pair of appendages on the margin adaxially. The addition of these three new taxa raises the total number of Mitrephora species in Thailand to 14. An identification key for Thai species is provided.

Greater hippocampal atrophy in developmental amnesia is associated with better recall and working memory performance.

Despite early-life bilateral hippocampal damage, developmental amnesic (DA) patients exhibit well-developed semantic memory, but severely impaired episodic retrieval. It is unclear, however, whether the residual hippocampus plays a role in encoding and/or retrieval of new information. Here, we report that in DA patients the extent of atrophy in CA-DG subregions and subicular complex is above 40% while the atrophy of the uncus is only moderate (-23%). Importantly, the perihippocampal cortices are unaffected. Paradoxically, patients' recall, Verbal IQ, Working Memory, and Processing Speed scores correlate negatively with the volume of the uncus. We propose that in DA patients, the uncus serves as "gatekeeper" providing signals that may inhibit compensatory mnemonic functions by the preserved surrounding cortical areas. Our findings highlight the role of uncus in recall, and document not only the extent, but also the limits of functional plasticity and circuit reorganization in the young brain after early bilateral hippocampal damage.

Neural correlates of category learning in monkey inferior temporal cortex.

We trained two monkeys implanted with multi-electrode arrays to categorize natural images of cats and dogs, in order to observe changes in neural activity related to category learning. We recorded neural activity from area TE, which is required for normal learning of visual categories based on perceptual similarity. Neural activity during a passive viewing task was compared pre- and post-training. After the category training, the accuracy of abstract category decoding improved. Specifically, the proportion of single units with category selectivity increased, and units sustained their category-specific responses for longer. Visual category learning thus appears to enhance category separability in area TE by driving changes in the stimulus selectivity of individual neurons and by recruiting more units to the active network.

Chemogenetic Disconnection between the Orbitofrontal Cortex and the Rostromedial Caudate Nucleus Disrupts Motivational Control of Goal-Directed Action.

The orbitofrontal cortex (OFC) and its major downstream target within the basal ganglia-the rostromedial caudate nucleus (rmCD)-are involved in reward-value processing and goal-directed behavior. However, a causal contribution of the pathway linking these two structures to goal-directed behavior has not been established. Using the chemogenetic technology of designer receptors exclusively activated by designer drugs with a crossed inactivation design, we functionally and reversibly disrupted interactions between the OFC and rmCD in two male macaque monkeys. We injected an adeno-associated virus vector expressing an inhibitory designer receptor, hM4Di, into the OFC and contralateral rmCD, the expression of which was visualized in vivo by positron emission tomography and confirmed by postmortem immunohistochemistry. Functional disconnection of the OFC and rmCD resulted in a significant and reproducible loss of sensitivity to the cued reward value for goal-directed action. This decreased sensitivity was most prominent when monkeys had accumulated a certain amount of reward. These results provide causal evidence that the interaction between the OFC and the rmCD is needed for motivational control of action on the basis of the relative reward value and internal drive. This finding extends the current understanding of the physiological basis of psychiatric disorders in which goal-directed behavior is affected, such as obsessive-compulsive disorder.SIGNIFICANCE STATEMENT In daily life, we routinely adjust the speed and accuracy of our actions on the basis of the value of expected reward. Abnormalities in these kinds of motivational adjustments might be related to behaviors seen in psychiatric disorders such as obsessive-compulsive disorder. In the current study, we show that the connection from the orbitofrontal cortex to the rostromedial caudate nucleus is essential for motivational control of action in monkeys. This finding expands our knowledge about how the primate brain controls motivation and behavior and provides a particular insight into disorders like obsessive-compulsive disorder in which altered connectivity between the orbitofrontal cortex and the striatum has been implicated.

Diversification Slowdown in the Cirrhopetalum Alliance (Bulbophyllum, Orchidaceae): Insights From the Evolutionary Dynamics of Crassulacean Acid Metabolism.

Evolutionary slowdowns in diversification have been inferred in various plant and animal lineages. Investigation based on diversification models integrated with environmental factors and key characters could provide critical insights into this diversification trend. We evaluate diversification rates in the Cirrhopetalum alliance (Bulbophyllum, Orchidaceae subfam. Epidendroideae) using a time-calibrated phylogeny and assess the role of Crassulacean acid metabolism (CAM) as a hypothesised key innovation promoting the spectacular diversity of orchids, especially those with an epiphytic habit. An explosive early speciation in the Cirrhopetalum alliance is evident, with the origin of CAM providing a short-term advantage under the low atmospheric CO2 concentrations (pCO2) associated with cooling and aridification in the late Miocene. A subsequent slowdown of diversification in the Cirrhopetalum alliance is possibly explained by a failure to keep pace with pCO2 dynamics. We further demonstrate that extinction rates in strong CAM lineages are ten times higher than those of C3 lineages, with CAM not as evolutionarily labile as previously assumed. These results challenge the role of CAM as a "key innovation" in the diversification of epiphytic orchids.

Goniothalamusroseipetalus and G.sukhirinensis (Annonaceae): Two new species from Peninsular Thailand.

Two new Goniothalamus species (Annonaceae), G.roseipetalus sp. nov. and G.sukhirinensis sp. nov., are described from the southern limits of Peninsular Thailand (Narathiwat and Yala Provinces). Both new species resemble G.macrophyllus, G.scortechinii and G.uvarioides. The addition of these two new species brings the total number of Goniothalamus species in Thailand to 27. Separate identification keys are provided for flowering and fruiting specimens of the Thai species.

Contributions of the Monkey Inferior Temporal Areas TE and TEO to Visual Categorization.

The ability to categorize images is thought to depend on neural processing within the ventral visual stream. Recently, we reported that after removal of architectonic area TE, the terminal region of the ventral stream, monkeys were still able to categorize images as cats or dogs moderately well. Here, we investigate the contribution of TEO, the architectonically defined region located one step earlier than area TE in the ventral stream. Bilateral removal of TEO caused only a mild impairment in categorization. However, combined TE + TEO removal was followed by a severe, long-lasting impairment in categorization. All of the monkeys tested, including those with combined TE + TEO removals, had normal low-level visual functions, such as visual acuity. These results support the conclusion that categorization based on visual similarity is processed in parallel in TE and TEO.

MRI monitoring of macaque monkeys in neuroscience: Case studies, resource and normative data comparisons.

Information from Magnetic Resonance Imaging (MRI) is useful for diagnosis and treatment management of human neurological patients. MRI monitoring might also prove useful for non-human animals involved in neuroscience research provided that MRI is available and feasible and that there are no MRI contra-indications precluding scanning. However, MRI monitoring is not established in macaques and a resource is urgently needed that could grow with scientific community contributions. Here we show the utility and potential benefits of MRI-based monitoring in a few diverse cases with macaque monkeys. We also establish a PRIMatE MRI Monitoring (PRIME-MRM) resource within the PRIMatE Data Exchange (PRIME-DE) and quantitatively compare the cases to normative information drawn from MRI data from typical macaques in PRIME-DE. In the cases, the monkeys presented with no or mild/moderate clinical signs, were well otherwise and MRI scanning did not present a significant increase in welfare impact. Therefore, they were identified as suitable candidates for clinical investigation, MRI-based monitoring and treatment. For each case, we show MRI quantification of internal controls in relation to treatment steps and comparisons with normative data in typical monkeys drawn from PRIME-DE. We found that MRI assists in precise and early diagnosis of cerebral events and can be useful for visualising, treating and quantifying treatment response. The scientific community could now grow the PRIME-MRM resource with other cases and larger samples to further assess and increase the evidence base on the benefits of MRI monitoring of primates, complementing the animals' clinical monitoring and treatment regime.

EARLY-ONSET LEUKOENCEPHALOMYELOPATHY AND POLYNEUROPATHY IN EASTERN QUOLLS (DASYURUS VIVERRINUS) IN THE EUROPEAN CAPTIVE POPULATION.

Leukoencephalomyelopathy (LEM) is suggested to be an age-related degenerative condition in geriatric Eastern quolls (Dasyurus viverrinus), manifesting in animals greater than 3.5 yr of age. This case series describes four LEM cases from two zoologic collections; three in nongeriatric animals, with one only 1 yr of age, and details advanced diagnostic investigation, including magnetic resonance imaging, cerebrospinal fluid analysis, and electrodiagnostic studies, not previously reported in Eastern quolls. Animals presented clinically with forelimb proprioceptive deficits and hindlimb and lumbar muscle hypotrophy, which were not noted in previous reports, in addition to hindlimb ataxia. Blindness and emaciation, which have been reported previously, were not seen. Disease progression was variable, and time from first clinical signs to euthanasia ranged from 46 days to over 2 yr. Histopathologic findings in the central nervous system were typical of those in previous LEM cases; concomitant polyneuropathy was observed in two quolls. Our findings suggest that age-related degeneration may not be the only cause of LEM in Eastern quolls. Because all quolls were related, a familial component cannot be excluded. LEM should be further investigated for its potential impact on future captive breeding programs, and our findings suggest that daily quality-of-life assessment should guide euthanasia of affected animals.

Specificity of assemblage, not fungal partner species, explains mycorrhizal partnerships of mycoheterotrophic Burmannia plants.

Mycoheterotrophic plants (MHPs) growing on arbuscular mycorrhizal fungi (AMF) usually maintain specialized mycorrhizal associations. The level of specificity varies between MHPs, although it remains largely unknown whether interactions with mycorrhizal fungi differ by plant lineage, species, and/or by population. Here, we investigate the mycorrhizal interactions among Burmannia species (Burmanniaceae) with different trophic modes using high-throughput DNA sequencing. We characterized the inter- and intraspecific dynamics of the fungal communities by assessing the composition and diversity of fungi among sites. We found that fully mycoheterotrophic species are more specialized in their fungal associations than chlorophyllous species, and that this specialization possibly results from the gradual loss of some fungal groups. In particular, although many fungal species were shared by different Burmannia species, fully MHP species typically host species-specific fungal assemblages, suggesting that they have a preference for the selected fungi. Although no apparent cophylogenetic relationship was detected between fungi and plants, we observe that evolutionarily closely related plants tend to have a greater proportion of shared or closely related fungal partners. Our findings suggest a host preference and specialization toward fungal assemblages in Burmannia, improving understanding of interactions between MHPs and fungi.