Longitudinal microstructural changes in 18 amygdala nuclei resonate with cortical circuits and phenomics.

The amygdala nuclei modulate distributed neural circuits that most likely evolved to respond to environmental threats and opportunities. So far, the specific role of unique amygdala nuclei in the context processing of salient environmental cues lacks adequate characterization across neural systems and over time. Here, we present amygdala nuclei morphometry and behavioral findings from longitudinal population data (>1400 subjects, age range 40-69 years, sampled 2-3 years apart): the UK Biobank offers exceptionally rich phenotyping along with brain morphology scans. This allows us to quantify how 18 microanatomical amygdala subregions undergo plastic changes in tandem with coupled neural systems and delineating their associated phenome-wide profiles. In the context of population change, the basal, lateral, accessory basal, and paralaminar nuclei change in lockstep with the prefrontal cortex, a region that subserves planning and decision-making. The central, medial and cortical nuclei are structurally coupled with the insular and anterior-cingulate nodes of the salience network, in addition to the MT/V5, basal ganglia, and putamen, areas proposed to represent internal bodily states and mediate attention to environmental cues. The central nucleus and anterior amygdaloid area are longitudinally tied with the inferior parietal lobule, known for a role in bodily awareness and social attention. These population-level amygdala-brain plasticity regimes in turn are linked with unique collections of phenotypes, ranging from social status and employment to sleep habits and risk taking. The obtained structural plasticity findings motivate hypotheses about the specific functions of distinct amygdala nuclei in humans

Temporal discrimination from the interaction between dynamic synapses and intrinsic subthreshold oscillations

The interaction between synaptic and intrinsic dynamics can efficiently shape neuronal input-output relationships in response to temporally structured spike trains. We use a neuron model with subthresh-old oscillations receiving inputs through a synapse with short-term depression and facilitation to show that the combination of intrinsic subthreshold and synaptic dynamics leads to channel-specific nontrivial responses and recognition of specific temporal structures. Our study employs the Generalized Integrate and-Fire (GIF) model, which can be subjected to analytical characterization. We map the temporal structure of spike input trains to the type of spike response, and show how the emergence of nontrivial input- output preferences is modulated by intrinsic and synaptic parameters in a synergistic manner. We demonstrate that these temporal input discrimination properties are robust to noise and to variations in synaptic strength. Furthermore, we also illustrate the presence of these input-output relationships in conductance-based models. Our results suggest a widespread computationally economic and easily tunable mechanism for temporal information discrimination in single neurons. (c) 2020 Elsevier B.V. All rights reserved.This work was supported AEI/FEDER grants FIS2017-84256-P (JJT) and PGC2018-095895-B-I00, DPI2015-65833-P (RL & PV)

Reliability of Eye Tracking and Pupillometry Measures in Individuals with Fragile X Syndrome

Recent insight into the underlying molecular and cellular mechanisms of fragile X syndrome (FXS) has led to the proposal and development of new pharmaceutical treatment strategies, and the initiation of clinical trials aimed at correcting core symptoms of the developmental disorder. Consequently, there is an urgent and critical need for outcome measures that are valid for quantifying specific symptoms of FXS and that are consistent across time. We used eye tracking to evaluate test–retest reliability of gaze and pupillometry measures in individuals with FXS and we demonstrate that these measures are viable options for assessing treatment-specific outcomes related to a core behavioral feature of the disorder

FMR1 premutation and full mutation molecular mechanisms related to autism

Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5′ un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are important for synaptic development and plasticity. Furthermore, many of these genes, when mutated, have been linked to autism in the general population, which may explain the high comorbidity that exists between FXS and autism spectrum disorders (ASD). Additionally, premutation repeat expansions (55 to 200 CGG repeats) may also give rise to ASD through a different molecular mechanism that involves a direct toxic effect of FMR1 mRNA. It is believed that RNA toxicity underlies much of the premutation-related involvement, including developmental concerns like autism, as well as neurodegenerative issues with aging such as the fragile X-associated tremor ataxia syndrome (FXTAS). RNA toxicity can also lead to mitochondrial dysfunction, which is common in older premutation carriers both with and without FXTAS. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in idiopathic autism. Research regarding dysregulation of neurotransmitter systems caused by the lack of FMRP in FXS, including metabotropic glutamate receptor 1/5 (mGluR1/5) pathway and GABA pathways, has led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism

Hypothalamic-pituitary-adrenal axis function in Fragile X Syndrome and its relationship to behaviour: A systematic review

Fragile X Syndrome (FXS) is characterised by features including anxiety and autistic-like behaviour, which led to early hypotheses that aberrant physiological arousal may underlie the behavioural phenotype. In line with this, several lines of evidence suggest that the hypothalamic-pituitary-adrenal (HPA) axis may be altered in the syndrome. This review collates evidence to determine the nature of HPA axis baseline activity and reactivity (as measured by glucocorticoid levels) differences in FXS, and its relationship to behaviour. Through a search of electronic databases, 15 papers were identified which provided data on humans with FXS or the FMR1 knockout mouse model. The findings across studies are mixed, though trends in the findings can be seen, including elevations in cortisol levels, particularly in males. Preliminary findings also highlight associations between cortisol levels and key behaviours associated with the syndrome, such as gaze avoidance. Areas for future research are discussed

Complexity on the Periphery: A Study of Regional Organization at Banavasi, c.1st - 18th Century A.D.

This dissertation uses archaeological and historical approaches to discuss the organization of a complex polity that lay in what has been considered a ‘peripheral’ zone in peninsular India, located outside the core areas of larger states and empires. Through a systematic survey of a 50 sq. km area at Banavasi, a regional capital, I analyze the long-term archaeological landscape to discuss changes in socio-religious and political organization as the area cycled into and out of political centrality. I conclude by proposing a tentative model for Banavasi as a nodal point. First, I argue that, although located in a peripheral area, Banavasi can be considered a regional center of some permanence- a ‘peripheral core’. Banavasi’s importance lies in part in its early development as a regional administrative and sacred center. Archaeologically, the sacred landscape of Banavasi reveals several of the complex processes of the legitimation of power, both of intermediate elite groups and of groups higher in the political hierarchy. By the tenth century, this involved a relationship of elite patronage and Brahmanical legitimation that drew on established patterns elsewhere in the subcontinent. Banavasi provided a space where this interaction between political and religious power could be displayed through the construction of Brahmanical temples or the donation of land. Second, Banavasi’s development can be linked to the presence of an intermediate elite family that appropriated the Banavasi area as their ‘core’. Through an analysis of a corpus of early inscriptions, issued by the Kadamba dynasty and dated between the fourth and seventh centuries AD, I consider some of the networks of alliances with larger political entities and with ones on a similar scale that structured the Banavasi area during this period. In this dissertation I have questioned the idea that peripheral regions were necessarily static entities by highlighting the complex nature of inter-regional interaction and the development of socio-political complexity, including the role of intermediate elites, in these areas. I also suggest that in a context of cycling and ephemeral states and empires, smaller but long-lived peripheral areas characterized by small centers and elite families are essential units of historical analysis.PhDAnthropologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/97865/1/uthara_1.pd

Book review: H. P. Ray, Coastal Shrines and Transnational Maritime Networks Across India and Southeast Asia

H. P. Ray, Coastal Shrines and Transnational Maritime Networks Across India and Southeast Asia. Routledge, 2021 Hardback, 255 pages, ISBN: 978-0-3677-0804-7 Price: ₹995. </jats:p

Book review: Upinder Singh, ed., The World of India’s First Archaeologist: Letters from Alexander Cunningham to J. D. M. Beglar

Upinder Singh, ed., The World of India’s First Archaeologist: Letters from Alexander Cunningham to J. D. M. Beglar. Delhi: Oxford University Press, 2021. </jats:p