Neuroscience Letters

Left-right asymmetry of the brain is well recognized in various animals including C. elegans, drosophila and zebrafish. In primates, most of the brain studies describe side of the brain. However, in spite of huge amounts of accumulating rodent studies on neuroscience, most of rodent studies do not distinguish the brain side. The pig brain is considered to occupy an intermediate position between primates and rodents in terms of structural complexity and brain function. Moreover, the numbers of studies using genetic manipulation of pigs are drastically increasing. So, we investigated microminipig (MMP) brain mesoscopic anatomy focusing on left-right differences of its morphology. Here, we show the anterior cingulate cortex, perirhinal cortex, and cerebellum of male and female MMPs, are structurally asymmetrical. The cerebellar vermis, paravermis is tilted from the midline and the consequently the cerebellar cortex exhibits asymmetrical morphology. The anterior cingulate gurus exhibited protrusion and invagination toward the midline on the right and left side, respectively. The left perirhinal lobe exhibited distinct patterns of cortical gyration between left and right side. These data demonstrate that MMPs are one of the suitable model animals for investigating cerebral and cerebellar asymmetry.

Traumatic brain injuries (TBIs) result from impact to or rapid displacement of the brain and can lead to various neurological deficits involving working memory, decision-making, and anxiety. While large-scale effects of brain damage are well-described for more severe TBIs, less is known about the extent and duration of cognitive deficits at the mild level. Interval timing can provide a helpful window into cognition in mice and humans. Interval-timing behavior is impaired in a wide range of neuropsychiatric disease states, such as Parkinsons disease. Furthermore, novel object recognition (NOR) and the Barnes maze (BM) tests are valuable assays for evaluating spatial learning, working memory, and anxiety-like behavior in mice. Here, we employed a weight-drop model of mild TBI (mTBI) to investigate changes in internal cognitive states resulting from mTBI treatment. mTBI mice were not significantly impaired in either interval timing or NOR, but they demonstrated impaired spatial memory in the Barnes Maze. Interestingly, within-sex comparisons revealed impairments in male mTBI mice in the interval-timing task and the NOR, suggesting that male and female mice may be differently affected by mTBIs.

Traumatic brain injury (TBI) induces a series of neuropathological changes in the brain including neurogenesis, an important cellular response involved in brain repair and regeneration. TBI-enhanced neurogenesis in the dentate gyrus (DG) of the hippocampus is of particular importance due its contribution to learning and memory functions. In the neurogenic process, proliferation and differentiation of neural stem cells (NSCs) follow a well-characterized sequence controlled by many factors including Notch1, which plays essential roles in regulating NSC fate determination under physiological conditions in both developing and adult brains. Following TBI, the dynamic changes of NSCs and the involvement of Notch1 on their development at different stages post-injury are not fully characterized. In the current study, we examined the impact of TBI and Notch1 on NSCs proliferation, survival and neuronal differentiation. Utilizing transgenic mice with tamoxifen-induced GFP expression and Notch1 knock-out in nestin+ NSCs, we examined DG neurogenic response at acute, subacute and chronic stages following a moderate lateral fluid percussion injury. We found that TBI enhanced a proliferative response in the DG at the acute stage following injury; however, this injury response was abolished when Notch1 was conditionally deleted from nestin+ NSCs. We also found that injury and Notch1 deletion drove NSCs committing fate choice towards neuronal differentiation. The results of this study provides further knowledge regarding TBI-induced neurogenic response and Notch1 as the key regulating mechanism.

This systematic review examines the effects of neurodegeneration in rats and mice on ultrasonic vocalisation (USV) production and its underlying neuronal substrates. Neurodegenerative diseases, such as Parkinsons, Alzheimers, and frontotemporal degeneration, significantly impair communication abilities in humans. Animal models, particularly rats and mice, are widely used to study the underlying mechanisms of these disorders. One important aspect of neurodegeneration is its impact on ultrasonic vocalisations in rodents. USVs play a crucial role in social interaction, mating, and distress signalling, making them valuable behavioural biomarkers for neurological dysfunction. This review aims to synthesise existing research on how neurodegeneration affects USV production and its neuronal substrates in rodent models. Understanding these changes can provide insights into disease progression and facilitate the development of early diagnostic tools and therapeutic strategies. Studying USV impairments in animal models may help identify biomarkers relevant to human speech deficits in neurodegenerative diseases. By bridging the gap between preclinical and clinical research, this review contributes to the growing field of neurobehavioral biomarkers, which could ultimately improve early diagnosis and intervention in human neurodegenerative conditions.

Ferroptosis is a form of non-apoptotic cell death in which iron catalyzes the formation of reactive oxygen species, leading to lipid peroxidation. Experimentally, this process has recently been associated with seizures based on the increased levels of specific markers (4-hydroxynonenal and malondialdehyde) in the brain and plasma. Clinically, iron deposits have been identified in resected tissue from patients with refractory temporal lobe epilepsy. Quantitative susceptibility mapping (QSM) offers an opportunity to detect these accumulations in vivo. In this study, we investigated how pilocarpine-induced status epilepticus contributes to the generation of iron deposits in diverse cerebral regions and whether QSM can detect these deposits longitudinally. We scanned 14 animals (n=10 experimental; n=4 control) at five different time points (pre-status epilepticus induction and 1, 7, 14, 21 days post-induction) using QSM. We identified iron deposits in the caudate putamen, hippocampus, thalamus, and primary somatosensory cortex of experimental animals, which is consistent with histological findings. The initial size of the hippocampal iron deposits significantly increased over the following weeks. None of these effects was observed in the control animals. The presence of cerebral iron depositions in an animal model of pilocarpine-induced status epilepticus suggests that ferroptosis may be involved in the onset, development, and progression of spontaneous recurrent seizures. Furthermore, non-invasive, longitudinal in vivo mapping of brain iron deposits could be a potential imaging marker in neurological disorders such as epilepsy. Future experiments will be required to determine the origin of the iron and avoid its progressive accumulation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=70 SRC="FIGDIR/small/712677v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@14abf67org.highwire.dtl.DTLVardef@5c08fborg.highwire.dtl.DTLVardef@51c40forg.highwire.dtl.DTLVardef@1eb5f9_HPS_FORMAT_FIGEXP M_FIG C_FIG

Even if they have no dementia, some elderly people find it difficult to imagine the food they may want to eat. However, research into treatments for anorexia in elderly people has not progressed sufficiently due to the lack of a method that can easily measure brain function in clinical settings. In this study, we aim to clarify the relationship of food-dependent medial prefrontal cortex (MPFC) activity with food preference and intake frequency by functional near-infrared spectroscopy (fNIRS) to determine ways to treat the appetite loss and have difficulty in explain what they want to eat. For this purpose, we firstly establish the methodology using young participants experiment. All young participants were asked about their food preferences and intake frequency using a questionnaire, and they were instructed to look and then eat the control dish (CD: typical Japanese home-cooked meal) and their preferred dish (PD: each participant purchased the dish themselves on the day of the experiments) on separate days, and activity of MPFC in each participant was recorded by fNIRS. We found that activity of MPFC during "just-looking" and "eating" were affected by food intake habits and preference. Especially, activity of MPFC during CD eating was affected by food preference (has dislike food or not). We concluded that the activity of MPFC during eating of dishes varies depending on the food intake habits and fNIRS could be a potential technique for estimating such activity.

Angelman syndrome is a neurodevelopmental disorder caused by loss of the maternally inherited UBE3A allele and is characterized by severe cognitive, motor, and communication impairments. Increased delta (1- 4 Hz) activity on electroencephalogram (EEG) assessed by visual inspection and by spectral power analysis is a robust feature of the disorder in humans and rodent models and is used as a biomarker of Angelman syndrome. This aspect of the phenotype has not been evaluated in the recently developed pig model of Angelman syndrome. Here, we analyzed scalp EEG recordings from freely moving pigs carrying a maternal UBE3A deletion (UBE3A-/+) across three age groups to determine whether they recapitulate the delta power abnormalities characteristic of the disorder. UBE3A-/+ pigs exhibited elevated delta power during both wakefulness and sleep compared with wild-type littermates, with the largest differences observed during the awake state. The typical increase in delta power that accompanies the transition from wakefulness to sleep was also reduced in UBE3A-/+ pigs. These effects were observed across study groups, demonstrating that the maternal UBE3A-deletion pig model reproduces the elevated delta power EEG phenotype of Angelman syndrome. Our results establish noninvasive scalp EEG as a translationally relevant tool for assessing neural dysfunction in this large-animal model and provide a framework for preclinical therapeutic testing. This work strengthens the utility of the pig model for mechanistic studies and therapeutic development in Angelman syndrome.

ObjectiveTo test the effect of Isoflurane on synaptic transmission of cortico-cortical and thalamocortical projections to the auditory cortex, and investigate how it modulates cortical sensory information processing to produce unconsciousness. MethodsUsing murine auditory thalamocortical brain slices, afferent pathways from the medial geniculate body (MGB) and layer 1 of the proximal cortex were stimulated to evoke excitatory postsynaptic potentials (eEPSPs) in cortical neurons. Whole-cell recordings were made from pyramidal and fast-spiking neurons in layer 2/3 and layer 5. eEPSPs were evaluated along with intrinsic membrane properties in response to stimulation of both pathways with and without isoflurane. ResultsIsoflurane administration resulted in significant eEPSP amplitude reduction following stimulation of both thalamic and cortical pathways, in layer 2/3 (p=0.015, p<0.001) and layer 5 (p<0.001, p<0.001) pyramidal neurons; while it only significantly reduced eEPSP amplitude in fast-spiking interneurons with cortical stimulation (p<0.001). Overall, isoflurane preferentially suppressed synaptic responses to cortico-cortical stimulation compared to thalamocortical (p=0.0002). Under isoflurane, cortico-cortical compared to thalamocortical stimulation evoked eEPSPs with reduced 10-90% rise time in both layer 2/3 and 5 pyramidal neurons, and shorter latency layer 5 neurons. Paired pulse ratio was not changed by isoflurane application, although an interesting loss of depression trend appear in layer 5 pyramidal neurons stimulated by cortical activation. Additional intrinsic neuronal measurements revealed that isoflurane reduced spike threshold significantly in both layer 2/3 and layer 5 neurons, reduced spike latency in layer 2/3 neurons, and input resistance in layer 5 neurons. However, these intrinsic neuronal changes were not seen in fast-spiking interneurons. All isoflurane induced changes were reversible during wash out. ConclusionsApplication of 1% isoflurane to brain slices significantly reduced the amplitudes of eEPSPs and modulated intrinsic neuronal properties. The effects on eEPSP amplitude were greater for cortical stimulation compared to thalamic stimulation. Isoflurane modulated intrinsic neuronal firing properties in pyramidal neurons, but not in fast-spiking interneurons.

Both episodic memory and word retrieval have been linked to power decreases in the alpha and beta oscillatory bands, but these patterns have rarely been related to each other, partly due to a lack of methodological approaches available. In this explorative study, we investigate the similarities and dissimilarities in the oscillatory fingerprints of the retrieval of words and episodes by directly comparing the activity patterns across time, frequency, and space. We acquired electroencephalography (EEG) data of participants performing a language and an episodic memory task based on the same stimulus material. With a newly developed approach, we directly compared the source-reconstructed oscillatory activity using mutual information and a feature-impact analysis. While left temporal and frontal regions showed dissimilarities between the tasks, right-hemispheric parietal regions exhibited similarities. We speculate that this could indicate a homologous function of these regions, potentially sharing less-specific representations between the tasks. We further uncovered a dissociation of the alpha and beta bands regarding the similarity across tasks. While the beta band was dissimilar between word and episodic memory retrieval, the alpha band seemed to contribute to the similarity we observed in right parietal regions. Whether this points to a task-unspecific function of the alpha band or a functional role in the retrieval process of the presumed representations, remains to be determined. In summary, we present an approach to study similarity across tasks using the temporal, spectral, and spatial dimensions of EEG data, and present results of exploring the shared oscillatory fingerprints between episodic memory and word retrieval.

ObjectiveFinding indicators of early response to antidepressant treatment in EEG signals recorded from patients suffering from major depressive disorder. MethodsFunctional brain connectivity networks based on weighted imaginary coherence and weighted imaginary mean phase coherence were computed for 176 patients for 6 different EEG frequency bands. Cross-hemispheric connectivity (CH) and lateral asymmetry (LA) were estimated from these networks based on EEG signals recorded before the beginning of treatment (V is1) and one week after the start of the treatment (V is2). Repeated measures ANOVA was used to check for statistically significant changes in connectivity based on these measures at V is2 w.r.t. V is1. Post-hoc analysis was performed with multiple pairwise comparison tests to determine which group means were significantly different. ResultsIt was found that CHV is2 was significantly reduced w.r.t. CHV is1 in the {beta}1 [12.5 - 17.5 Hz] frequency band for the responders to treatment. Also, LAV is2 was significantly increased w.r.t. LAV is1 in the {beta}1 frequency band for the responders. No such significant changes were observed for the non-responders. Brain networks constructed using both weighted imaginary coherence and weighted imaginary mean phase coherence were found to exhibit these results. For the CH connectivity changes, binarized networks and for the LA connectivity changes, weighted networks were found to be more reliable. ConclusionsResponders were found to show a reduction in cross-hemispheric connectivity and an increase in lateral asymmetry, both in the {beta}1 band while no such change was observed for the non-responders. SignificanceDecrease in cross-hemispheric connectivity and increase in lateral asymmetry in the {beta}1 band may represent candidate neurophysiological indicators of early treatment response, but they require independent replication before any clinical application can be considered.

BackgroundThe hippocampus and medial temporal lobe are crucial for spatial memory, and their dysfunction is linked to Alzheimers disease (AD), with changes detectable even in preclinical stages. Recently, neuromodulation has gained interest as a potential treatment due to its beneficial effects on AD pathology and cognitive performance. However, outcomes vary significantly based on stimulation parameters and study conditions, and evidence from large animal models remains limited. ObjectiveTo assess whether epicranial current stimulation (ECS) at 40 Hz can improve non-navigational spatial memory and hippocampal activations. MethodsThree rhesus macaques were implanted with spiral platinum electrodes bilaterally on the skull and were trained in a non-navigational spatial memory task. ECS was applied at 40 Hz or at 10 Hz and performance across multiple sessions was evaluated. We further performed ECS during fMRI to examine the spread of activations caused by ECS across the brain in a block-design experiment. ResultsECS at 40 Hz improved performance in a non-navigational spatial memory task, while 10 Hz ECS had minimal or negative effects. Concurrent ECS-fMRI showed extensive brain activations at 40 Hz, including significant hippocampal activations, which was not observed at 10 Hz. ConclusionsOur results show that ECS could be a minimally-invasive and effective approach to improve memory performance and activate the hippocampus. ECS could represent a potential treatment for patients suffering from memory impairment.

Voltage-gated sodium channels (VGSCs) are conventionally described as heterotrimers composed of one alpha and two beta subunits. However, the patterns of co-expression of alpha- and beta-subunits in neurons remain unclear. In the present study, we report that alpha- (Nav1.1, Nav1.2, and Nav1.6) and beta- (beta-1 and beta-2) subunits are densely expressed in axon initial segments (AISs) of neurons in the neocortex, hippocampus and cerebellum at postnatal days 14-15 (P14-15) and 8-9 weeks (8-9W). These distributions are largely unique and partially overlapping among brain regions. Notably, in the neocortex and hippocampus, AISs of presumptive parvalbumin-positive inhibitory neurons are positive for Nav1.1 and beta-1, whereas those of excitatory ones are positive for Nav1.2 and beta-2. Similarly, AISs of cerebellar basket cells, which are inhibitory neurons, are positive for Nav1.1 and beta-1, whereas those of granule cells, which are excitatory neurons, are positive for Nav1.2 and beta-2. Nav1.6 is expressed in many of these neurons. Some subunits exhibited distinct distribution patterns at the two postnatal stages analyzed, possibly because of their developmental changes of subcellular localizations. Taken together, these results indicate that combinations of VGSC subunits are largely unique among different neuronal subpopulations. These findings provide a useful reference for understanding the distribution and interactions of VGSC subunits in the brain.

Rise time (RT) is considered to be one of the most significant acoustical characteristics of auditory speech stimuli. A substantial amount of data has been accumulated on the neurophysiological mechanisms of RT processing under different conditions and in different groups of people, but these data have not been systematised. This review focuses on studies that have investigated electroencephalographic (EEG) markers of RT sensitivity. The present literature search was conducted according to the PRISMA statement in PubMed, Web of Science and APA PsychInfo databases. The resultant review comprised 37 studies that considered diverse aspects of RT processing. The review describes the main stimulation parameters affecting electrophysiological markers of RT processing reflected in different components of event-related potentials, brainstem responses and cortical rhythmic activity. The main finding of this review is that the rise time prolongation leads to a decrease in the amplitude of the main ERP components and an increase in their latencies. However, the sensitivity of the EEG markers varied with the earliest components tracking the subtle difference (few tens of microseconds), while the later components coding the larger one (up to 500 ms). Nevertheless, the observed effects may vary and depend on some aspects of the experimental paradigm, age of participants and speech-related problems. Future research may benefit by addressing understudied clinical groups and ERP components such as P1 and N2, dominated in children.

Sexual motivation is a complex concept involving both the initial drive to begin mating and the motivation to sustain copulation. Disruptions in sexual motivation are often observed in psychiatric disorders. This study proposes that sexual motivation can be divided into two distinct components: sexual incentive motivation and the drive to sustain copulation. To investigate this, we utilized the Motivation to Continue Copulation (MCC) test, which measures effort (nose pokes) to gain access to a sexual reward, and compared it with the Sexual Incentive Motivation (SIM) test and standard copulation tests. Male and female rats were trained on a fixed ratio (FR) 1 schedule using cheese rewards before transitioning to sexual rewards. After six FR1 sessions, the effort required increased to FR5 and progressive ratio (PR) schedules. Results revealed that sexual incentive motivation, measured by the SIM test, was higher in males after sexual experience, while females maintained consistent levels. In the MCC test, both males and females exhibited increased motivation to continue copulation with experience, but the motivation declined in the 2nd ejaculatory series. These findings demonstrate that sexual motivation comprises distinct components. The MCC test effectively measures the drive to sustain copulation, while the SIM test assesses incentive motivation. This distinction is crucial for advancing behavioral neuroscience and understanding sexual dysfunction in psychiatric conditions.

BackgroundParkinsons disease (PD) is a progressive chronic neurodegenerative disease. The PARK2 gene encoding the Parkin protein accounts for approximately half of early-onset autosomal recessive PD cases in humans. ObjectiveThe aim of this work was to study the effect of the PARK2 gene knockout in mice on the dynamics of behavioral and biochemical parameters of PD. MethodsThe study was performed on C57BL/6-line mice aged from 4 months to 1.5 years: wild type (park2 +/+), heterozygotes (park2 +/-) and homozygotes (park2 -/-) knocked out by the PARK2 using CRISPR-Cas9. The open field test, the Porsolt forced swimming test, the grid-walk test, the beam-walking test, the elevated plus maze test, the accelerating rotarod test were used to assess the behavioral phenotype. Measurement of the concentration of bioamines and their metabolites by HPLC and evaluation of the amount of tyrosine hydroxylase, BDNF and GDNF by Western Blot were used to study the biochemical signs of PD. ResultsPark2 -/- mice begin to show signs of decreased motor activity no earlier than at 4 months of life. At 12 months of life, it was shown only a decrease in the level of the mature isoform of GDNF and an increase in the number of immature isoforms in the frontal cortex and striatum were revealed. ConclusionThe data obtained indicates a different age dynamic of the condition of mice associated with the PARK2 knockout. However, no pronounced specific manifestations of PD in human were found in park2 -/- mice.

Previous research indicates that chronic intraperitoneal (ip) administration of the GABAB receptor agonist baclofen reduces body weight gain in rats without altering daily food intake. The present study was undertaken to extend these observations by investigating the effects of chronic ip administration of the potent GABAB receptor agonist 3-aminopropyl (methyl) phosphinic acid (SKF-97541) on daily changes on body weight and food intake in free feeding rats. The animals were injected ip once daily with SKF-97541 (0.1 mg / kg for 5 days, followed by 0.2 mg / kg for 8 days; Experiment 1) or SKF-97542 (0.4 mg / kg) for 17 days (Experiment 2). Control animals received physiological saline in both experiments. While daily food intake did not differ significantly between groups, the SKF-97541 group exhibited significant reductions in body weight gain compared to controls. These results extend previous findings and show that systemic administration of SKF-97541 suppresses weight gain independently of caloric intake, and lend further support to the hypothesis that GABAB receptor agonists decrease body weight primarily by increasing metabolic rate.

Schizophrenia is a severe neuropsychiatric disorder characterized by positive and negative symptoms and cognitive impairments. The present study aimed to investigate the potential interference of ambient noise on the performance of executive function (EF) tasks in individuals with schizophrenia. The sample consisted of 40 participants, divided equally into two groups: a group of individuals with schizophrenia (SchG) and a healthy control group without neuropsychiatric disorders (HC). All participants did three EF assessment instruments: Trail Making Test, Corsi Block Test, and Maze Test. The experimental design included a test-retest procedure with order counterbalancing: half of the sample began the assessment in the noise condition and the other half in the no-noise condition, to control for order and learning effects. The results indicate that ambient noise has a negative impact on the cognitive performance of individuals with schizophrenia. Specifically, the SchG group performed significantly worse on the Maze Test in the noise condition compared to the no-noise condition. These findings contribute to the understanding of the interactions between sensory and cognitive processes underlying the symptoms of schizophrenia. In addition to their theoretical potential, the results have practical implications, as they support the development of intervention strategies and ambiental adaptations that can improve the functionality and quality of life of people with the disorder.

Neural activity in mouse primary visual cortex (V1) correlates strongly with orofacial movements. Such strong modulation has not been found in the primate visual cortex during eye fixation [1], which led to the suggestion that the modulation may primarily depend on eye movements in both species [2]. Here we examined the influence of eye movements on neural activity in mouse visual cortex both in complete darkness and in the presence of different types of visual input. In all cases, we found that eye movements explain a smaller fraction of neural activity variance compared to orofacial behaviors. Additionally, we found that eye movements were correlated to orofacial movements, such as whisking and sniffing, and thus may be indirectly correlated to neural activity. These results further emphasize the impact of movement signals on mouse visual cortex during free viewing behavior.

Brain-computer interfaces (BCIs) have immense potential regarding the provision of therapies for disorders of development, but to date have typically been created for non-linguistic disorders such as ADHD (attention deficit hyperactivity disorder). Here we present a BCI that aims to improve linguistic phonological processing in developmental dyslexia. Phonological deficits are considered a core feature of dyslexia across languages. A non-invasive EEG-BCI relying on auditory inputs and visual feedback was developed to optimise brain patterns related to phonology (speech-sound processing). These patterns were identified using Temporal Sampling (TS) theory, which proposes that phonological difficulties in dyslexia are related to impaired auditory processing of amplitude envelope rise times and low-frequency speech envelope information <10 Hz. These impairments are thought to affect automatic features of speech processing from birth, impairing the development of a phonological system. Adults with and without a diagnosis of developmental dyslexia played the BCI for 16 sessions, and received pre-and post-testing regarding phonological awareness and single word and nonword reading skills. Significant associations between their BCI scores (a measure of BCI learning) and improvements in syllable stress discrimination, nonword reading and amplitude rise time discrimination were found. The data are interpreted with respect to TS theory.

Currently, implantation of electroencephalogram (EEG) electrodes in laboratory animals is time-consuming and requires specialized equipment. We present a novel method for EEG recordings in mice that utilizes thin needle electrodes. These electrodes are inserted into the skull at predetermined locations by gently pressing them against the bone surface. To ensure stable fixation of the implant, hook-shaped needles are positioned along the lateral aspects of the skull. The electrodes are connected to a multipin connector and secured to the skull using dental composite, after which the animal is allowed to recover from anesthesia. Importantly, procedures such as skull drilling and screw placement are not required, allowing the entire surgery to be completed in less than 15 minutes. Consequently, this EEG implantation approach is rapid and minimally invasive. Results of our studies indicate that EEG recordings obtained with needle electrodes are not inferior to those obtained with screw electrodes. Overall, the method is designed to enhance the accuracy and efficiency of EEG recording studies while improving animal welfare. O_LISimplifies the placement of EEG electrodes. C_LIO_LIReduces the time required for electrode implantation. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=67 SRC="FIGDIR/small/715731v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@e5608org.highwire.dtl.DTLVardef@1325ea4org.highwire.dtl.DTLVardef@1e37202org.highwire.dtl.DTLVardef@1521bb8_HPS_FORMAT_FIGEXP M_FIG C_FIG