Encoding Patterned Spatial Behavior in the Subiculum.

Background: The hippocampus is a gray matter collection within the medial temporal lobe and plays a vital role in memory and spatial navigation. This study aims to explore the cytoarchitecture of the hippocampal subfields in the cornu ammonis (CA) region, i.e. CA3, CA4, and dentate gyrus, its analysis of the thickness of layers (μ) and cellular dimensions (μ), and analysis of radial glial cells. Methodology: We studied the cytoarchitecture of hippocampal subfields in 21 human cadavers. The research involved detailed histological analysis of hippocampal subfields, i. e., CA3, CA4, and dentate gyrus, using hematoxylin and eosin staining, using ImageJ software to measure the cellular dimensions (μ) and thickness (μ) of each layer and the cells present within each layer. In additionally, immunohistochemical detection of glial fibrillary acidic protein (GFAP) was done to identify radial glial cells. Results: Significant differences in the thickness of hippocampal layers and cell sizes among the subfields were noted. Specifically, CA3 and CA4 subfields exhibit distinct structural features compared to the dentate gyrus, with CA4 showing a variation in layer differentiation. GFAP staining revealed variable expression across samples, reflecting the presence and activity of radial glial cells involved in neurogenesis and neural plasticity. Conclusion: The study enhances the understanding of hippocampal cytoarchitecture and its implications for brain function and neurogenesis.

The hippocampus, which is deeply involved in episodic memory, plays a pivotal role in spatial navigation, an essential animal behavior. Spatial navigation requires the calculation of the distance and direction from a current to the final position, i.e., a vector to a goal. Place cells in the mammalian hippocampus maximally increase their firing rates when the animal passes a particular location and then encode the animal's current location. The entorhinal cortex, one synapse upstream of the hippocampus, contains both grid and head direction cells that encode distance and direction information, respectively. However, the question of whether the hippocampus generates a vector for goal-directed navigation during the integration of distance and direction to the destination remains unclear. Mounting evidence of the cell types involved in spatial navigation has been obtained mainly in mammalian model animals such as rats and mice. Recent advances in wireless and miniaturized neural activity monitoring devices have begun to yield results not only in model organisms but also in wild mammals, birds, fish, and insects. A scrutiny of the literature examining neural correlates of spatial navigation across multiple animal species reveals that few place cells or grid cells have been found, but that head direction cells are commonly present in multiple animal species. Exceptionally, rodent-like place cells were only found in the medial pallium of tufted titmice, a food-caching bird. The medial pallium is an avian brain region homologous to the mammalian hippocampus. By contrast, rodent-like head direction cells are found in the medial pallium of quails. Head direction cells are also found in the medial pallium of streaked shearwaters, a migratory bird. The avian hippocampus contains information about the animal's current location or direction, but the neural encoding may differ depending on the ecological characteristics of the bird species. The place cells of bats, which are mammals, fly in three-dimensional space and encode vectorial information toward the goal. Training rats with an ingenious task that required them to choose a direction for each run in a maze suggested that place cells encode a vector for goal-directed spatial navigation. Thus, the scrutiny of the literature on spatial navigation-related neuronal activity across multiple animal species suggests that depending on a combination of external conditions such as the context in which the animal is situated (e.g., the context or the framework composed of landmarks in the environment) and internal conditions such as the ecological and behavioral characteristics of the animal, hippocampal neurons can be identified as place cells or head direction cells. We thus propose a conjecture that primitively, the hippocampus, or its homolog, contains information about the travel direction and that the emergence of the hippocampus during evolution has enabled the generation of vector information to the goal for advanced spatial navigation such as the search for the shortcut path and episodic memory capacity.

The medial temporal lobe (MTL) is known to support episodic memory and spatial navigation, raising the possibility that its true function is to form "cognitive maps" of any kind of information. Studies in humans and animals support the idea that the hippocampal theta rhythm (4 to 8 Hz) is key to this mapping function, as it has been repeatedly observed during spatial navigation tasks. If episodic memory and spatial navigation are 2 sides of the same coin, we hypothesized that theta oscillations might reflect relations between explicitly nonspatial items, such as words. We asked 189 neurosurgical patients to perform a verbal free-recall task, of which 96 had indwelling electrodes placed in the MTL. Subjects were instructed to remember short lists of sequentially presented nouns. We found that hippocampal theta power and connectivity during item retrieval coded for semantic distances between words, as measured using word2vec-derived subspaces. Additionally, hippocampal theta indexed temporal distances between words after filtering lists on recall performance, to ensure adequate dynamic range in time. Theta effects were noted only for semantic subspaces of 1 dimension, indicating a substantial compression of the possible semantic feature space. These results lend further support to our growing confidence that the MTL forms cognitive maps of arbitrary representational spaces, helping to reconcile longstanding differences between the spatial and episodic memory literatures.

Observing that the ‘hemispheres’ are essentially a mammalian structure, Edinger (1910) applied the term ‘palaeocerebellum’ to the vermis and flocculus and the term ‘neocerebellum’ to the remainder (Fig. 3). Hausman (1929), elaborating on this concept, stated that a neocerebellar equivalent has been provided for each lobule of the vermis except the lingula. Although useful and expressive, the terms neo‐ and palaeocerebellum have been used by many different authors to designate somewhat different cerebellar parts, and unless qualified or limited have at present no certain meaning. Further, as Winkler (1923) and others have emphasized repeatedly, new acquisitions to the cerebellum take the form of growth of preexisting parts rather than altogether new structures superimposed on the old. The identification of the vermis, as defined by Edinger, as a morphological entity is misleading and lacks morphological or functional support. Hausman's identification of all lateral cerebellar parts with the neocerebellum seems hardly justified when we realize that both ontogenetically and phylogenetically the cerebellum had a bilateral origin, and that even in man one of the lateral parts, the flocculus, appears very early in the development of the cerebellum. The term neocerebellum has some meaning if reserved for those parts which in the higher mammals have come to be dominated by cortico‐pontine connexions; but such a definition allows for no hard and fast delimitation by particular fissures. If the rest of the cerebellum is then designated palaeocerebellum, it must be recognized that it contains subdivisions of varying phylogenetic age. From a functional point of view probably the most important single contribution to cerebellar morphology is that of Sven Ingvar (1918) (Fig. 4). In his earlier monographic work he combines comparative morphological observations, fibre connexion studies, pathological and physiological investigations in an attempt to subdivide correctly the cerebellum. He was impressed with the uniformity of the lobules anterior to the fissura prima and posterior to the fissura prepyramidalis and with the wide variation in the lobules between these two deep and constant fissures in many species of birds and mammals. He noted the presence of two fissures which appeared to correspond to those in the alligator. A case of cerebellar atrophy which was restricted largely to the lobes lying between the primary and prepyramidal fissures was described, and the distribution of the spino‐cerebellar fibres rostral and caudal to these fissures was also pointed out. Using all this evidence, Ingvar divided the cerebellum into three lobes, anterior, middle and posterior. This division, however, was less illuminating than a second concept which he emphasized later (Ingvar, 1928). This second classification was based on the distribution of afferent fibre connexions. He presented it in a novel way by comparing the cerebellum to a three‐story house. The ‘basement’ consisted of the lobes receiving direct vestibular root fibres, which included the nodulus, uvula, lingula and flocculus. The next story he called the spinal floor. It consists of the lobules anterior to the fissura prima, the pyramis and paraflocculus. The remaining lobes which received predominantly ponto‐cerebellar fibres he called the ‘cerebral floor’. This last division has in recent years been frequently identified by the term ‘neocerebellum’. Summary A review of previous work which has influenced cerebellar terminology is presented. An effort is made to harmonize the various sets of terms applied to lobes and fissures of the mammalian cerebellum with each other and with the terminology of human anatomy. The points in which agreement cannot yet be found and on which homologies with human anatomy are not clear are emphasized. The phylogenetic development of the cerebellum is described with particular attention to the contributions of Larsell in Amphibia, reptiles and primitive mammals. A schema of the folial pattern which seems best suited for the whole vertebrate system is presented, which is designed to show fundamental morphological principles and at the same time to conserve those terms now in most frequent use. The embryological development of the mammalian cerebellum is described in the light of the findings in lower forms. The phylogenetic and ontogenetic importance of the postero‐lateral fissure of Larsell and the fundamental difference between the flocculus and paraflocculus of the mammalian cerebellum is stressed. A detailed description of the histology of the cerebellar cortex in mammals is given. Recent advances in the study of the afferent fibre connexions to the cerebellum are brought out and contributions of oscillographic studies emphasized. Each afferent system is analysed in detail both as to origin and termination in the cerebellum. Particular attention is given to the important cortico‐ponto‐cerebellar system of the higher mammals and the most recent analysis of the olivocerebellar connexion by Brodal. The functional localization in the cerebellum on the basis of the afferent fibre connexions is pointed out. It is emphasized that the termination of the afferent fibres does not favour topographical localization within the respective vestibular, spinal and cortico‐pontine parts of the cerebellum. The common features of the vestibulo‐cerebellar, spino‐cerebellar and pontocerebellar systems are mentioned as well as the fact that the olivo‐cerebellar system seems to be distinct from the other afferent systems. A suggestion is made that the mossy fibre endings are from the vestibular, spinal and pontine systems, while the olivo‐cerebellar system terminates as climbing fibres. Available evidence, both for and against this conception, is discussed in some detail. Recent findings on the cerebellar cortico‐nuclear connexions are presented. The development of the mammalian cerebellar nuclei and their homologies with the nuclei of the human cerebellum are discussed. It is pointed out that until such homologies are better established than at present it is impossible to transfer data from animal experiments to man in so far as the connexions of the globose nucleus is concerned. The efferent connexions of the deep cerebellar nuclei, as determined experimentally, are described in detail. The lack of available anatomical evidence for topographical localization on the basis of efferent cerebellar connexions is pointed out.

Modulation of associative learning in the hippocampal-striatal circuit based on item-set similarity

Spatial Navigation

Midbrain periaqueductal grey region in the cat has afferent and efferent connections with solitary tract nuclei

Investigations into how individual neurons encode behavioral variables of interest have revealed specific representations in single neurons, such as place and object cells, as well as a wide range of cells with conjunctive encodings or mixed selectivity. However, as most experiments examine neural activity within individual tasks, it is currently unclear if and how neural representations change across different task contexts. Within this discussion, the medial temporal lobe is particularly salient, as it is known to be important for multiple behaviors including spatial navigation and memory, however the relationship between these functions is currently unclear. Here, to investigate how representations in single neurons vary across different task contexts in the medial temporal lobe, we collected and analyzed single-neuron activity from human participants as they completed a paired-task session consisting of a passive-viewing visual working memory and a spatial navigation and memory task. Five patients contributed 22 paired-task sessions, which were spike sorted together to allow for the same putative single neurons to be compared between the different tasks. Within each task, we replicated concept-related activations in the working memory task, as well as target-location and serial-position responsive cells in the navigation task. When comparing neuronal activity between tasks, we first established that a significant number of neurons maintained the same kind of representation, responding to stimuli presentations across tasks. Further, we found cells that changed the nature of their representation across tasks, including a significant number of cells that were stimulus responsive in the working memory task that responded to serial position in the spatial task. Overall, our results support a flexible encoding of multiple, distinct aspects of different tasks by single neurons in the human medial temporal lobe, whereby some individual neurons change the nature of their feature coding between task contexts.

The hippocampus plays an important role in spatial navigation and spatial learning across a variety of vertebrate species. Sex and seasonal differences in space use and behavior are known to affect hippocampal volume. Similarly, territoriality and differences in home range size are known to affect the volume of the reptile hippocampal homologues, the medial and dorsal cortices (MC, DC). However, studies have almost exclusively investigated males and little is known about sex or seasonal differences in MC and/or DC volumes in lizards. Here, we are the first to simultaneously examine sex and seasonal differences in MC and DC volumes in a wild lizard population. In Sceloporus occidentalis, males display territorial behaviors that are more pronounced during the breeding season. Given this sex difference in behavioral ecology, we expected males to have larger MC and/or DC volumes than females and for this difference to be most pronounced during the breeding season when territorial behavior is increased. Male and female S. occidentalis were captured from the wild during the breeding season and the post-breeding season and were sacrificed within 2 days of capture. Brains were collected and processed for histology. Cresyl-violet-stained sections were used to quantify brain region volumes. In these lizards, breeding females had larger DC volumes than breeding males and nonbreeding females. There was no sex or seasonal difference in MC volumes. Differences in spatial navigation in these lizards may involve aspects of spatial memory related to breeding other than territoriality that affect plasticity of the DC. This study highlights the importance of investigating sex differences and including females in studies of spatial ecology and neuroplasticity.

Deletion of the serotonin receptor type 7 disrupts the acquisition of allocentric but not egocentric navigation strategies in mice

Top-down attention is a dynamic cognitive process that facilitates the detection of the task-relevant stimuli from our complex sensory environment. A neural mechanism capable of deployment under specific task-demand conditions would be crucial to efficiently control attentional processes and improve promote goal-directed attention performance during fluctuating attentional demand. Previous studies have shown that frontal top-down neurons projecting from the anterior cingulate area (ACA) to the visual cortex (VIS; ACAVIS) are required for visual attentional behavior during the 5-choice serial reaction time task (5CSRTT) in mice. However, it is unknown whether the contribution of these projecting neurons is dependent on the extent of task demand. Here, we first examined how behavior outcomes depend on the number of locations for mice to pay attention and touch for successful performance, and found that the 2-choice serial reaction time task (2CSRTT) is less task demanding than the 5CSRTT. We then employed optogenetics to demonstrate that suppression ACAVIS projections immediately before stimulus presentation has no effect during the 2CSRTT in contrast to the impaired performance during the 5CSRTT. These results suggest that ACAVIS projections are necessary when task demand is high, but once a task demand is lowered, ACAVIS neuron activity becomes dispensable to adjust attentional performance. These findings support a model that the frontal-sensory ACAVIS projection regulates visual attention behavior during specific high task demand conditions, pointing to a flexible circuit-based mechanism for promoting attentional behavior.

Subnuclear organization of the efferent connections of the parabrachial nucleus in the rat

What connections can we draw between fMRI and neural firing patterns? The basic requirement of differencing in neuroimaging has limitations because subtraction of baseline activity removes an important part of the total activity 1. Our prior studies have quantitatively revealed that most neurons in the ensemble (in a voxel) contribute differently before, during, and after the stimulation 2. Since the ensemble activity of pyramidal neurons in layer 4 depends on sensory (or localized) input by the thalamus and global (or delocalized) input from other cortical regions, delocalized signals from a global workspace may affect localized stimulus-induced responses. To test the hypothesis that delocalized signals, which have been proposed to include subjective contributions 3, can modulate localized signals we conducted fMRI and electrophysiological studies in rats under varied conditions of anesthesia and forepaw stimulation. The fMRI experiments of -chloralose (40 mg/kg/hr) and halothane (0.7%) anesthetized rats were conducted on 7.0 T or 9.4 T systems using calibrated fMRI 1, 2. The electrical activity was measured by Tungsten microelectodes. The extracellular signals were filtered to separate field and action potentials (FP, AP), where the AP data were binned for spiking frequency. While the fMRI data from both baselines (i.e., halothane and -chloralose) showed sensory-induced changes in the contralateral primary somatosensory and motor areas, there were increased delocalized activities observed with (light) halothane anesthesia. These regions were ipsilateral primary somatosensory, contralateral secondary somatosensory, as well as perirhinal and retrosplenial agranular areas. In contrast signals from delocalized regions were notably absent with (deep) -chloralose anesthesia. These results were supported by correlated changes in AP and FP time courses. The spiking frequency distributions measured from the most activated foci in the contralateral (and ipsilateral) primary somatosensory area(s). The contralateral distributions with (deep) -chloralose anesthesia showed a significant shift from low to high frequency values upon stimulation. The contralateral distribution shift was less noteworthy with (light) halothane anesthesia. The distributions for the baselines with halothane and -chloralose were significantly different, in which the degrees of global inputs assigned to higher frequencies dominated under (light) halothane anesthesia. The contralateral distributions upon stimulation with halothane and -chloralose were also significantly different, suggesting that under the (light) halothane anesthesia level the global inputs dominated whereas local changes were dominated under the (deep) -chloralose anesthesia. Since neuronal populations in different regions do not function as modules, the resultant fMRI or electrophysiological activity patterns arise from interactions of afferent and efferent connections – the latter of which was modulated by anesthesia in this study. These results provide the initial steps to explore the interactions of localized and delocalized underpinnings of the concept of the global workspace model 3 (See Figure 1).

The purpose of this study was to determine to what extent the cat parastriate cortex processes afferent geniculate activity in a way similar to that in area 17. The area explored was located on the lateral gyrus between the Horsley-Clarke coordinates A1 to 4 and L3 to 4. The receptive-field properties of area 18 cells and their responses to electrical stimulation of afferent and efferent pathways were measured with the same methods as described previously in area 17. Mutual correlations among these items were calculated and compared with the respective data from area 17. The results of this correlative analysis revealed numerous similarities between the two areas with regard to their afferent and efferent connections and their intrinsic organization. Consequently, the structure of the receptive fields and their numerical distribution resembled those in area 17. The same was true for the correlations between receptive-field parameters and afferent and efferent connectivity. The main differences were that area 18 cells had larger receptive fields and responded to considerably higher stimulus velocities. It is suggest-d that these differences are caused by the fact that area 18 receives subcortical afferents of the Y-type, whereas the dominant input to area 17 comes from the X-system. It is concluded that the area investigated in this study is organized in parallel to area 17 and deals with other aspects of visual information than area 17.

Representation of Spatial Goals in Rat Orbitofrontal Cortex