We reliably judge locations of static objects when we walk despite the retinal images of these objects moving with every step we take. Here, we showed our brains solve this optical illusion by adopting an allocentric spatial reference frame. We measured perceived target location after the observer walked a short distance from the home base. Supporting the allocentric coding scheme, we found the intrinsic bias , which acts as a spatial reference frame for perceiving location of a dimly lit target in the dark, remained grounded at the home base rather than traveled along with the observer. The path-integration mechanism responsible for this can utilize both active and passive (vestibular) translational motion signals, but only along the horizontal direction. This asymmetric path-integration finding in human visual space perception is reminiscent of the asymmetric spatial memory finding in desert ants, pointing to nature\'s wondrous and logically simple design for terrestrial creatures.

Tramadol and tapentadol are chemically related opioids prescribed for the analgesia of moderate to severe pain. Although safer than classical opioids, they are associated with neurotoxicity and behavioral dysfunction, which arise as a concern, considering their central action and growing misuse and abuse. The hippocampal formation is known to participate in memory and learning processes and has been documented to contribute to opioid dependence. Accordingly, the present study assessed molecular and cellular alterations in the hippocampal formation of Wistar rats intraperitoneally administered with 50 mg/kg tramadol or tapentadol for eight alternate days. Alterations were found in serum hydrogen peroxide, cysteine, homocysteine, and dopamine concentrations upon exposure to one or both opioids, as well as in hippocampal 8-hydroxydeoxyguanosine and gene expression levels of a panel of neurotoxicity, neuroinflammation, and neuromodulation biomarkers, assessed through quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of hippocampal formation sections showed increased glial fibrillary acidic protein (GFAP) and decreased cluster of differentiation 11b (CD11b) protein expression, suggesting opioid-induced astrogliosis and microgliosis. Collectively, the results emphasize the hippocampal neuromodulator effects of tramadol and tapentadol, with potential behavioral implications, underlining the need to prescribe and use both opioids cautiously.

UNASSIGNED: The chromosome 1p32p31 deletion syndrome is a contiguous gene disorder with a variable phenotype characterized by brain malformations with or without urinary tract defects, besides neurodevelopmental delay and dysmorphisms. An expanded phenotype was proposed based on additional findings, including one previous report of a patient presenting with moyamoya disease.
UNASSIGNED: The authors report a patient presenting with early neurodevelopmental delay, hydrocephalus, renal malformation, and dysmorphisms. After presenting with a sudden choreic movement disorder, the neuroimaging investigation revealed an ischemic stroke, moyamoya disease, and bilateral incomplete hippocampal inversion. Chromosomal microarray analysis revealed a deletion of 13.2 Mb at 1p31.3p32.2, compatible with the contiguous gene syndrome caused by microdeletions of this region.
UNASSIGNED: This is the second report of a patient who developed Moyamoya disease and the first to describe bilateral incomplete hippocampal inversion in this microdeletion syndrome.

Vertebrate hippocampal formation is central to conversations on the comparative analysis of spatial cognition, especially in light of variation found in different vertebrate classes. Assuming the medial pallium (MP) of extant amphibians resembles the hippocampal formation (HF) of ancestral stem tetrapods, we propose that the HF of modern amniotes began with a MP characterized by a relatively undifferentiated cytoarchitecture, more direct thalamic/olfactory sensory inputs, and a more generalized role in associative learning-memory processes. As such, hippocampal evolution in amniotes, especially mammals, can be seen as progressing toward a cytoarchitecture with well-defined subdivisions, regional connectivity, and a functional specialization supporting map-like representations of space. We then summarize a growing literature on amphibian spatial cognition and its underlying brain organization. Emphasizing the MP/HF, we highlight that further research into amphibian spatial cognition would provide novel insight into the role of the HF in spatial memory processes, and their supporting neural mechanisms. A more complete reconstruction of hippocampal evolution would benefit from additional research on non-mammalian vertebrates, with amphibians being of particular interest.

Although the hippocampus is one of the most-studied brain regions in mammals, research on the avian hippocampus has been more limited in scope. It is generally agreed that the hippocampus is an ancient feature of the amniote brain, and therefore homologous between the two lineages. Because birds and mammals are evolutionarily not very closely related, any shared anatomy is likely to be crucial for shared functions of their hippocampi. These functions, in turn, are likely to be essential if they have been conserved for over 300 million years. Therefore, research on the avian hippocampus can help us understand how this brain region evolved and how it has changed over evolutionary time. Further, there is a strong research foundation in birds on hippocampal-supported behaviors such as spatial navigation, food caching, and brood parasitism that scientists can build upon to better understand how hippocampal anatomy, network circuitry, endocrinology, and physiology can help control these behaviors. In this review, we summarize our current understanding of the avian hippocampus in spatial cognition as well as in regulating anxiety, approach-avoidance behavior, and stress responses. Although there are still some questions about the exact number of subdivisions in the avian hippocampus and how that might vary in different avian families, there is intriguing evidence that the avian hippocampus might have complementary functional profiles along the rostral-caudal axis similar to the dorsal-ventral axis of the rodent hippocampus, where the rostral/dorsal hippocampus is more involved in cognitive processes like spatial learning and the caudal/ventral hippocampus regulates emotional states, anxiety, and the stress response. Future research should focus on elucidating the cellular and molecular mechanisms - including endocrinological - in the avian hippocampus that underlie behaviors such as spatial navigation, spatial memory, and anxiety-related behaviors, and in so doing, resolve outstanding questions about avian hippocampal function and organization.

Damage to the hippocampus produces profound retrograde amnesia, but odour and object discrimination memories can be spared in the retrograde direction. Prior lesion studies testing retrograde amnesia for object/odour discriminations are problematic due to sparing of large parts of the hippocampus, which may support memory recall, and/or the presence of uncontrolled, distinctive odours that may support object discrimination. To address these issues, we used a simple object discrimination test to assess memory in male rats. Two visually distinct objects, paired with distinct odour cues, were presented. One object was associated with a reward. Following training, neurotoxic hippocampal lesions were made using N-methyl-D-aspartate (NMDA). The rats were then tested on the preoperatively learned object discrimination problem, with and without the availability of odour or visual cues during testing. The rats were also postoperatively trained on a new object discrimination problem. Lesion sizes ranged from 67% to 97% of the hippocampus (average of 87%). On the preoperatively learned discrimination problem, the rats with hippocampal lesions showed preserved object discrimination memory when tested in the dark (i.e., without visual cues) but not when the explicit odour cues were removed from the objects. Hippocampal lesions increased the number of trials required to reach criterion but did not prevent rats from solving the postoperatively learned discrimination problem. Our results support the idea that long-term memories for odours, unlike recall of visual properties of objects, do not depend on the hippocampus in rats, consistent with previous observations that hippocampal damage does not cause retrograde amnesia for odour memories.

The behavioral and neural mechanisms that support spatial cognition have been an enduring interest of psychologists, and much of that enduring interest is attributable to the groundbreaking research of Ken Cheng. One manifestation of this interest, inspired by the idea of studying spatial cognition under natural field conditions, has been research carried out to understand the role of the avian hippocampal formation (HF) in supporting homing pigeon navigation. Emerging from that research has been the conclusion that the role of HF in homing pigeon navigation aligns well with the canonical narrative of a hippocampus important for spatial memory and the implementation of such memories to support navigation. However, recently an accumulation of disparate observations has prompted a rethinking of the avian HF as a structure also important in shaping visual-spatial perception or attention antecedent to any memory processing. In this perspective paper, we summarize field observations contrasting the behavior of intact and HF-lesioned homing pigeons from several studies, based primarily on GPS-recorded flight paths, that support a recharacterization of HF\'s functional profile to include visual-spatial perception. Although admittedly still speculative, we hope the offered perspective will motivate controlled, experimental-laboratory studies to further test the hypothesis of a HF important for visual-perceptual integration, or scene construction, of landscape elements in support of navigation.

Hippocampal CA3 is traditionally conceptualized as a brain region within a unidirectional feedforward trisynaptic pathway that links major hippocampal subregions. Recent genomic and viral tracing studies indicate that the anatomical connectivity of CA3 and the trisynaptic pathway is more complex than initially expected and suggests that there may be cell type-specific input gradients throughout the three-dimensional hippocampal structure. In several recent studies using multiple viral tracing approaches, we describe subdivisions of the subiculum complex and ventral hippocampal CA1 that show significant back projections to CA1 and CA3 excitatory neurons. These novel connections form \"noncanonical\" circuits that run in the opposite direction relative to the well-characterized feedforward pathway. Diverse subtypes of GABAergic inhibitory neurons participate within the trisynaptic pathway. In the present study, we have applied monosynaptic retrograde viral tracing to examine noncanonical synaptic inputs from CA1 and subicular complex to the inhibitory neuron in hippocampal CA3. We quantitatively mapped synaptic inputs to CA3 inhibitory neurons to understand how they are connected within and beyond the hippocampus formation. Major brain regions that provide typical inputs to CA3 inhibitory neurons include the medial septum, the dentate gyrus, the entorhinal cortex, and CA3. Noncanonical inputs from ventral CA1 and subicular complex to CA3 inhibitory neurons follow a proximodistal topographic gradient with regard to CA3 subregions. We find novel noncanonical circuit connections between inhibitory CA3 neurons and ventral CA1, subiculum complex, and other brain regions. These results provide a new anatomical connectivity basis to further study the function of CA3 inhibitory neurons.

Little information is available on the magnetic resonance imaging (MRI) determination of the hippocampal formation (HF) during the perinatal period. However, this exploration is increasingly used, which requires defining visible HF landmarks on MRI images, validated through histological analysis. This study aims to provide a protocol to identify HF landmarks on MRI images, followed by histological validation through serial sections of the temporal lobe of the samples examined, to assess the longitudinal extent of the hippocampus during the perinatal period. We examined ex vivo MRI images from nine infant control brain samples. Histological validation of the hippocampal formation MRI images was obtained through serial sectioning and examination of Nissl-stained sections at 250 μm intervals along the entire length of the hippocampal formation. Up to six landmarks were identified both in MRI images and the serial histological sections. Proceeding in an anterior to posterior (rostrocaudal) direction, these were as follows: 1) the limen insulae (fronto-temporal junction); 2) the beginning of the amygdaloid complex; 3) the beginning of the lateral ventricle; 4) the caudal limit of the uncus, indicated by the start of the lateral geniculate nucleus (at the level of the gyrus intralimbicus); 5) the end of the lateral geniculate nucleus (beginning of the pulvinar); and 6) the beginning of the fornix. After histological validation of each of these landmarks, the full longitudinal length of the hippocampal formation and distances between landmarks were calculated. No statistically significant differences were found in total length or between landmarks. While the HF is anatomically organized at birth, its annotation is particularly challenging to perform. The histological validation of HF landmarks allows a better understanding of MRI images. The proposed protocol could be useful to assess MRI hippocampal quantification in children and possible variations due to different neurological diseases.

The hippocampal formation and entorhinal cortex are crucially involved in learning and memory as well as in spatial navigation. The conservation of these structures across the entire mammalian lineage demonstrates their importance. Information on a diverse set of spatially tuned neurons has become available, but we only have a rudimentary understanding of how anatomical network structure affects functional tuning. Bats are the only order of mammals that have evolved true flight, and with this specialization comes the need to navigate and behave in a three dimensional (3D) environment. Spatial tuning of cells in the entorhinal-hippocampal network of bats has been studied for some time, but whether the reported tuning in 3D is associated with changes in the entorhinal-hippocampal network is not known. Here we investigated the entorhinal-hippocampal projections in the Egyptian fruit bat (Rousettus aegyptiacus), by injecting chemical anterograde tracers in the entorhinal cortex. Detailed analyses of the terminations of these projections in the hippocampus showed that both the medial and lateral entorhinal cortex sent projections to the molecular layer of all subfields of the hippocampal formation. Our analyses showed that the terminal distributions of entorhinal fibers in the hippocampal formation of Egyptian fruit bats-including the proximo-distal and longitudinal topography and the layer-specificity-are similar to what has been described in other mammalian species such as rodents and primates. The major difference in entorhinal-hippocampal projections that was described to date between rodents and primates is in the terminal distribution of the DG projection. We found that bats have entorhinal-DG projections that seem more like those in primates than in rodents. It is likely that the latter projection in bats is specialized to the behavioral needs of this species, including 3D flight and long-distance navigation.