Mapping the distribution of Nipah virus infections: a geospatial modelling analysis.

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.

The global distribution and the risk prediction of relapsing fever group Borrelia: a data review with modelling analysis.

BACKGROUND: The recent discovery of emerging relapsing fever group Borrelia (RFGB) species, such as Borrelia miyamotoi, poses a growing threat to public health. However, the global distribution and associated risk burden of these species remain uncertain. We aimed to map the diversity, distribution, and potential infection risk of RFGB. METHODS: We searched PubMed, Web of Science, GenBank, CNKI, and eLibrary from Jan 1, 1874, to Dec 31, 2022, for published articles without language restriction to extract distribution data for RFGB detection in vectors, animals, and humans, and clinical information about human patients. Only articles documenting RFGB infection events were included in this study, and data for RFGB detection in vectors, animals, or humans were composed into a dataset. We used three machine learning algorithms (boosted regression trees, random forest, and least absolute shrinkage and selection operator logistic regression) to assess the environmental, ecoclimatic, biological, and socioeconomic factors associated with the occurrence of four major RFGB species: Borrelia miyamotoi, Borrelia lonestari, Borrelia crocidurae, and Borrelia hermsii; and mapped their worldwide risk level. FINDINGS: We retrieved 13 959 unique studies, among which 697 met the selection criteria and were used for data extraction. 29 RFGB species have been recorded worldwide, of which 27 have been identified from 63 tick species, 12 from 61 wild animals, and ten from domestic animals. 16 RFGB species caused human infection, with a cumulative count of 26 583 cases reported from Jan 1, 1874, to Dec 31, 2022. Borrelia recurrentis (17 084 cases) and Borrelia persica (2045 cases) accounted for the highest proportion of human infection. B miyamotoi showed the widest distribution among all RFGB, with a predicted environmentally suitable area of 6·92 million km2, followed by B lonestari (1·69 million km2), B crocidurae (1·67 million km2), and B hermsii (1·48 million km2). The habitat suitability index of vector ticks and climatic factors, such as the annual mean temperature, have the most significant effect among all predictive models for the geographical distribution of the four major RFGB species. INTERPRETATION: The predicted high-risk regions are considerably larger than in previous reports. Identification, surveillance, and diagnosis of RFGB infections should be prioritised in high-risk areas, especially within low-income regions. FUNDING: National Key Research and Development Program of China.

Comparison of head direction cell firing characteristics across thalamo-parahippocampal circuitry.

Head direction (HD) cells, which fire persistently when an animal's head is pointed in a particular direction, are widely thought to underlie an animal's sense of spatial orientation and have been identified in several limbic brain regions. Robust HD cell firing is observed throughout the thalamo-parahippocampal system, although recent studies report that parahippocampal HD cells exhibit distinct firing properties, including conjunctive aspects with other spatial parameters, which suggest they play a specialized role in spatial processing. Few studies, however, have quantified these apparent differences. Here, we performed a comparative assessment of HD cell firing characteristics across the anterior dorsal thalamus (ADN), postsubiculum (PoS), parasubiculum (PaS), medial entorhinal (MEC), and postrhinal (POR) cortices. We report that HD cells with a high degree of directional specificity were observed in all five brain regions, but ADN HD cells display greater sharpness and stability in their preferred directions, and greater anticipation of future headings compared to parahippocampal regions. Additional analysis indicated that POR HD cells were more coarsely modulated by other spatial parameters compared to PoS, PaS, and MEC. Finally, our analyses indicated that the sharpness of HD tuning decreased as a function of laminar position and conjunctive coding within the PoS, PaS, and MEC, with cells in the superficial layers along with conjunctive firing properties showing less robust directional tuning. The results are discussed in relation to theories of functional organization of HD cell tuning in thalamo-parahippocampal circuitry.

Anatomical projections to the dorsal tegmental nucleus and abducens nucleus arise from separate cell populations in the nucleus prepositus hypoglossi, but overlapping cell populations in the medial vestibular nucleus.

Specialized circuitry in the brain processes spatial information to provide a sense of direction used for navigation. The dorsal tegmental nucleus (DTN) is a core component of this circuitry and utilizes vestibular inputs to generate neural activity encoding the animal's directional heading. Projections arising from the nucleus prepositus hypoglossi (NPH) and the medial vestibular nucleus (MVe) are thought to transmit critical vestibular signals to the DTN and other brain areas, including the abducens nucleus (ABN), a component of eye movement circuitry. Here, we utilized a dual retrograde tracer approach in rats to investigate whether overlapping or distinct populations of neurons project from the NPH or MVe to the DTN and ABN. We report that individual MVe neurons project to both the DTN and ABN. In contrast, we observed individual NPH neurons that project to either the DTN or ABN, but rarely to both structures simultaneously. We also examined labeling patterns in other structures located in the brainstem and posterior cortex and observed (1) complex patterns of interhemispheric connectivity between the left and right DTN, (2) projections from the supragenual nucleus, interpeduncular nucleus, and retrosplenial cortex to the DTN, (3) projections from the lateral superior olive to the ABN, and (4) a unique population of cerebrospinal fluid-contacting neurons in the dorsal raphe nucleus. Collectively, our experiments provide valuable new information that extends our understanding of the anatomical organization of the brain's spatial processing circuitry.

A Comparison of Neural Decoding Methods and Population Coding Across Thalamo-Cortical Head Direction Cells.

Head direction (HD) cells, which fire action potentials whenever an animal points its head in a particular direction, are thought to subserve the animal's sense of spatial orientation. HD cells are found prominently in several thalamo-cortical regions including anterior thalamic nuclei, postsubiculum, medial entorhinal cortex, parasubiculum, and the parietal cortex. While a number of methods in neural decoding have been developed to assess the dynamics of spatial signals within thalamo-cortical regions, studies conducting a quantitative comparison of machine learning and statistical model-based decoding methods on HD cell activity are currently lacking. Here, we compare statistical model-based and machine learning approaches by assessing decoding accuracy and evaluate variables that contribute to population coding across thalamo-cortical HD cells.

Functional and anatomical relationships between the medial precentral cortex, dorsal striatum, and head direction cell circuitry. II. Neuroanatomical studies.

An animal's directional heading within its environment is encoded by the activity of head direction (HD) cells. In rodents, these neurons are found primarily within the limbic system in the interconnected structures that form the limbic HD circuit. In our accompanying report in this issue, we describe two HD cell populations located outside of this circuit in the medial precentral cortex (PrCM) and dorsal striatum (DS). These extralimbic areas receive their HD signals from the limbic system but do not provide critical input or feedback to limbic HD cells (Mehlman ML, Winter SS, Valerio S, Taube JS. J Neurophysiol 121: 350-370, 2019.). In this report, we complement our previous lesion and recording experiments with a series of neuroanatomical tracing studies in rats designed to examine patterns of connectivity between the PrCM, DS, limbic HD circuit, and related spatial processing circuitry. Retrograde tracing revealed that the DS receives direct input from numerous structures known to contain HD cells and/or other spatially tuned cell types. Importantly, these projections preferentially target and converge within the most medial portion of the DS, the same area in which we previously recorded HD cells. The PrCM receives direct input from a subset of these spatial processing structures. Anterograde tracing identified indirect pathways that could permit the PrCM and DS to convey self-motion information to the limbic HD circuit. These tracing studies reveal the anatomical basis for the functional relationships observed in our lesion and recording experiments. Collectively, these findings expand our understanding of how spatial processing circuitry functionally and anatomically extends beyond the limbic system into the PrCM and DS. NEW & NOTEWORTHY Head direction (HD) cells are located primarily within the limbic system, but small populations of extralimbic HD cells are found in the medial precentral cortex (PrCM) and dorsal striatum (DS). The neuroanatomical tracing experiments reported here explored the pathways capable of transmitting the HD signal to these extralimbic areas. We found that projections arising from numerous spatial processing structures converge within portions of the PrCM and DS that contain HD cells.

Functional and anatomical relationships between the medial precentral cortex, dorsal striatum, and head direction cell circuitry. I. Recording studies.

Head direction (HD) cells fire as a function of the animal's directional heading and provide the animal with a sense of direction. In rodents, these neurons are located primarily within the limbic system, but small populations of HD cells are found in two extralimbic areas: the medial precentral cortex (PrCM) and dorsal striatum (DS). HD cell activity in these structures could be driven by output from the limbic HD circuit or generated intrinsically. We examined these possibilities by recording the activity of PrCM and DS neurons in control rats and in rats with anterodorsal thalamic nucleus (ADN) lesions, a manipulation that disrupts the limbic HD signal. HD cells in the PrCM and DS of control animals displayed characteristics similar to those of limbic HD cells, and these extralimbic HD signals were eliminated in animals with complete ADN lesions, suggesting that the PrCM and DS HD signals are conveyed from the limbic HD circuit. Angular head velocity cells recorded in the PrCM and DS were unaffected by ADN lesions. Next, we determined if the PrCM and DS convey necessary self-motion signals to the limbic HD circuit. Limbic HD cell activity recorded in the ADN remained intact following combined lesions of the PrCM and DS. Collectively, these experiments reveal a unidirectional functional relationship between the limbic HD circuit and the PrCM and DS; the limbic system generates the HD signal and transmits it to the PrCM and DS, but these extralimbic areas do not provide critical input or feedback to limbic HD cells. NEW & NOTEWORTHY Head direction (HD) cells have been extensively studied within the limbic system. The lesion and recording experiments reported here examined two relatively understudied populations of HD cells located outside of the canonical limbic HD circuit in the medial precentral cortex and dorsal striatum. We found that HD cell activity in these two extralimbic areas is driven by output from the limbic HD circuit, revealing that HD cell circuitry functionally extends beyond the limbic system.

Multisensory and Motor Representations in Rat Oral Somatosensory Cortex.

In mammals, a complex array of oral sensors assess the taste, temperature and haptic properties of food. Although the representation of taste has been extensively studied in the gustatory cortex, it is unclear how the somatosensory cortex encodes information about the properties of oral stimuli. Moreover, it is poorly understood how different oral sensory modalities are integrated and how sensory responses are translated into oral motor actions. To investigate whether oral somatosensory cortex processes food-related sensations and movements, we performed in vivo whole-cell recordings and motor mapping experiments in rats. Neurons in oral somatosensory cortex showed robust post-synaptic and sparse action potential responses to air puffs. Membrane potential showed that cold water evoked larger responses than room temperature or hot water. Most neurons showed no clear tuning of responses to bitter, sweet and neutral gustatory stimuli. Finally, motor mapping experiments with histological verification revealed an initiation of movements related to food consumption behavior, such as jaw opening and tongue protrusions. We conclude that somatosensory cortex: (i) provides a representation of the temperature of oral stimuli, (ii) does not systematically encode taste information and (iii) influences orofacial movements related to food consummatory behavior.

Retrosplenial cortex is required for the retrieval of remote memory for auditory cues.

The restrosplenial cortex (RSC) has a well-established role in contextual and spatial learning and memory, consistent with its known connectivity with visuo-spatial association areas. In contrast, RSC appears to have little involvement with delay fear conditioning to an auditory cue. However, all previous studies have examined the contribution of the RSC to recently acquired auditory fear memories. Since neocortical regions have been implicated in the permanent storage of remote memories, we examined the contribution of the RSC to remotely acquired auditory fear memories. In Experiment 1, retrieval of a remotely acquired auditory fear memory was impaired when permanent lesions (either electrolytic or neurotoxic) were made several weeks after initial conditioning. In Experiment 2, using a chemogenetic approach, we observed impairments in the retrieval of remote memory for an auditory cue when the RSC was temporarily inactivated during testing. In Experiment 3, after injection of a retrograde tracer into the RSC, we observed labeled cells in primary and secondary auditory cortices, as well as the claustrum, indicating that the RSC receives direct projections from auditory regions. Overall our results indicate the RSC has a critical role in the retrieval of remotely acquired auditory fear memories, and we suggest this is related to the quality of the memory, with less precise memories being RSC dependent.

Passive Transport Disrupts Grid Signals in the Parahippocampal Cortex.

Navigation is usually thought of relative to landmarks, but neural signals representing space also use information generated by an animal's movements. These signals include grid cells, which fire at multiple locations, forming a repeating grid pattern. Grid cell generation depends upon theta rhythm, a 6-10 Hz electroencephalogram (EEG) oscillation that is modulated by the animals' movement velocity. We passively moved rats in a clear cart to eliminate motor related self-movement cues that drive moment-to-moment changes in theta rhythmicity. We found that passive movement maintained theta power and frequency at levels equivalent to low active movement velocity, spared overall head-direction (HD) cell characteristics, but abolished both velocity modulation of theta rhythmicity and grid cell firing patterns. These results indicate that self-movement motor cues are necessary for generating grid-specific firing patterns, possibly by driving velocity modulation of theta rhythmicity, which may be used as a speed signal to generate the repeating pattern of grid cells.

Spatial context learning in pigeons (Columba livia).

In a seminal paper in the cognitive sciences, Chun and Jiang (1998) described the contextual cueing paradigm in which they used artificial stimuli and showed that people became faster to locate a target when the background predicted the location of a target compared to when it did not. Here we examined contextual cueing in pigeons for the first time using artificial stimuli and procedures similar to those of Chun and Jiang. In the first test, we had pigeons search for a target among a display of seven distractors; during one condition, the position of the distractors predicted the location of the target, and in the second condition, there was no relationship between the two. In a second test, we presented the pigeons with the predictive displays from Test 1 and a second set of displays that also predicted the location of a target to see if learning about one set of predictive backgrounds disrupted learning about a second set. The pigeons were quick to acquire context-based knowledge and retain that information when faced with additional contexts. The results suggest that contextual cueing can occur for a variety of stimuli in nonhuman animals and that it may be a common mechanism for processing visual information across a wide variety of species.