Organisation of cingulum bundle fibres connecting the anterior thalamic nuclei with the rodent anterior cingulate and retrosplenial cortices

Despite considerable interest in the properties of the cingulum bundle, descriptions of the composition of this major pathway in the rodent brain have not kept pace with advances in tract tracing. Using complementary approaches in rats and mice, this study examined the dense, reciprocal connections the anterior thalamic nuclei have with the cingulate and retrosplenial cortices, connections thought to be major contributors to the rodent cingulum bundle. The rat data came from a mixture of fluorescent and viral tracers, some injected directly into the bundle. The mouse data were collated from the Allen Mouse Brain Atlas. The projections from the three major anterior thalamic nuclei occupied much of the external medullary stratum of the cingulum bundle, where they were concentrated in its more medial portions. These anterior thalamic projections formed a rostral-reaching basket of efferents prior to joining the cingulum bundle, with anteromedial efferents taking the most rostral routes, often reaching the genu of the corpus callosum, while anterodorsal efferents took the least rostral route. In contrast, the return cortico-anterior thalamic projections frequently crossed directly through the bundle or briefly joined the internal stratum of the cingulum bundle, often entering the internal capsule before reaching the anterior thalamus. These analyses confirm that anterior thalamic connections comprise an important component of the rodent cingulum bundle, while also demonstrating the very different routes used by thalamo-cortical and cortico-thalamic projections. This information reveals how the composition of the cingulum bundle alters along its length

The cingulum bundle: anatomy, function, and dysfunction

The cingulum bundle is a prominent white matter tract that interconnects frontal, parietal, and medial temporal sites, while also linking subcortical nuclei to the cingulate gyrus. Despite its apparent continuity, the cingulum’s composition continually changes as fibres join and leave the bundle. To help understand its complex structure, this review begins with detailed, comparative descriptions of the multiple connections comprising the cingulum bundle. Next, the impact of cingulum bundle damage in rats, monkeys, and humans is analysed. Despite causing extensive anatomical disconnections, cingulum bundle lesions typically produce only mild deficits, highlighting the importance of parallel pathways and the distributed nature of its various functions. Meanwhile, non-invasive brain imaging implicates the cingulum bundle in executive control, emotion, pain (dorsal cingulum), and episodic memory (parahippocampal cingulum), while clinical studies reveal cingulum abnormalities in numerous conditions, including schizophrenia, depression, post-traumatic stress disorder, obsessive compulsive disorder, autism spectrum disorder, Mild Cognitive Impairment, and Alzheimer’s disease. Understanding the seemingly diverse contributions of the cingulum will require better ways of isolating pathways within this highly complex tract

Chemogenetics reveal an anterior cingulate-thalamic pathway for attending to task-relevant information

In a changing environment, organisms need to decide when to select items that resemble previously rewarded stimuli and when it is best to switch to other stimulus types. Here, we used chemogenetic techniques to provide causal evidence that activity in the rodent anterior cingulate cortex and its efferents to the anterior thalamic nuclei modulate the ability to attend to reliable predictors of important outcomes. Rats completed an attentional set-shifting paradigm that first measures the ability to master serial discriminations involving a constant stimulus dimension that reliably predicts reinforcement (intradimensional-shift), followed by the ability to shift attention to a previously irrelevant class of stimuli when reinforcement contingencies change (extradimensional-shift). Chemogenetic disruption of the anterior cingulate cortex (Experiment 1) as well as selective disruption of anterior cingulate efferents to the anterior thalamic nuclei (Experiment 2) impaired intradimensional learning but facilitated 2 sets of extradimensional-shifts. This pattern of results signals the loss of a corticothalamic system for cognitive control that preferentially processes stimuli resembling those previously associated with reward. Previous studies highlight a separate medial prefrontal system that promotes the converse pattern, that is, switching to hitherto inconsistent predictors of reward when contingencies change. Competition between these 2 systems regulates cognitive flexibility and choice

A Near-infrared Variability Survey of Young Planetary-mass Objects

We present a photometric variability survey of young planetary-mass objects using the New Technology Telescope in the Js and Ks bands. Surface gravity plays an important role in the atmospheric structure of brown dwarfs, as young low gravity L dwarfs have a higher variability rate than field L dwarfs. In this study, we extend variability studies to young T-type planetary-mass objects and investigate the effects of surface gravity on the variability of L and T dwarfs across a large sample. We conduct continuous monitoring for 18 objects with spectral types from L5 to T8 and detect four new variables and two variable candidates. Combining with previous variability surveys of field and young L and T objects, we find that young objects tend to be more variable than field objects within peak-to-peak variability amplitude ranges of 0.5-10 per cent and period ranges of 1.5-20 hr. For the first time, we constrain the variability rate of young T dwarfs to be 56 per cent compared to 25 per cent for field T dwarfs. Both field and young samples have higher variability rates at the L/T transition than outside the L/T transition. The differences in the variability rates between field and young samples are about 1 sigma and therefore larger sample sizes are needed to confirm and refine the results. Besides the L/T transition, young L dwarfs with strong variability tend to assemble in a narrow spectral type range of L6-L7.5. This work supports the critical role of surface gravity on the atmospheric structure from L to T spectral types.Comment: Accepted for publication in MNRAS, 21 pages of main text including 6 tables and 17 figure

The Anatomical Boundary of the Rat Claustrum

The claustrum is a subcortical nucleus that exhibits dense connectivity across the neocortex. Considerable recent progress has been made in establishing its genetic and anatomical characteristics, however, a core, contentious issue that regularly presents in the literature pertains to the rostral extent of its anatomical boundary. The present study addresses this issue in the rat brain. Using a combination of immunohistochemistry and neuroanatomical tract tracing, we have examined the expression profiles of several genes that have previously been identified as exhibiting a differential expression profile in the claustrum relative to the surrounding cortex. The expression profiles of parvalbumin (PV), crystallin mu (Crym), and guanine nucleotide binding protein (G protein), gamma 2 (Gng2) were assessed immunohistochemically alongside, or in combination with cortical anterograde, or retrograde tracer injections. Retrograde tracer injections into various thalamic nuclei were used to further establish the rostral border of the claustrum. Expression of all three markers delineated a nuclear boundary that extended considerably (∼500 μm) beyond the anterior horn of the neostriatum. Cortical retrograde and anterograde tracer injections, respectively, revealed distributions of cortically-projecting claustral neurons and cortical efferent inputs to the claustrum that overlapped with the gene marker-derived claustrum boundary. Finally, retrograde tracer injections into the thalamus revealed insular cortico-thalamic projections encapsulating a claustral area with strongly diminished cell label, that extended rostral to the striatum

Cingulate cortex-anterior thalamic connectivity: Anatomy and function

The cingulum bundle is a highly complex fibre pathway that is implicated in a wide array of functions, yet little is known about its constituent connections and their differential contributions to cognition. This thesis investigated the dense interconnections between the cingulate cortices and the anterior thalamic nuclei, many of which join the cingulum. Initially, contemporary viral-based tract tracing techniques in the rat provided an anatomical reappraisal of this major component of the tract. This investigation revealed that many fibres between the anterior cingulate cortex and the anteromedial thalamic nucleus are present in the anterior cingulum, a subsection typically associated with executive function. Connections between the retrosplenial cortex and the anteroventral thalamic nucleus, meanwhile, primarily occupy the posterior cingulum, a subsection linked to memory. Next, this thesis investigated the role of anterior cingulate-anterior thalamic interconnectivity in attention. Existing evidence implicates both regions in intradimensional set-shifting, where discriminations are most effectively solved by responding to a stimulus dimension that previously predicted reward. A series of DREADDs manipulations confirmed that the anterior cingulate cortex supports this attentional function in rats, and novel evidence indicated that projections to the anterior thalamic nuclei critically contribute to this capacity. This thesis further found that in the absence of normal anterior cingulate function, inappropriate attention appears to be directed to unreliable reward predictors, facilitating performance when contingencies change (extradimensional shift). These findings are best explained by dual-process theories of attention where competing learning parameters, with distinct neural underpinnings, mediate the allocation of attentional resources. One process directs attention to reliable predictors of outcomes (reliant on the anterior cingulate cortex and its actions on the anterior thalamic nuclei), while another biases attention towards unreliable predictors of outcome

Community Change in an Eastern Indiana Forest Following Removal of an Invasive Shrub, Lonicera maackii (Family: Caprifoliaceae)

Lonicera maackii (Amur Honeysuckle) is a dominant invasive shrub species in many forests in the Midwestern United States. In this study, we examined the effects of L. maackii within 4 mid-successional forest plots, 2 of which have had L. maackii removed annually since 2004. We investigated whether L. maackii is competing with both native adult trees and tree seedling by exploiting sunlight and soil resources, and therefore reducing adult growth, seedling cover, and seedling distribution. Overall, our evidence indicates that L. maackii reduces native seedling height and density by shading and that L. maackii inhibits community successions. Its removal allows certain native tree seedlings to colonize. There was no indication of reduced adult tree growth in the presence of L. maackii. There was also no evidence that L. maackii changes soil organic matter, moisture, nutrients, or pH. Our study directly confirms L. maackii as a “driver” for ecological change mainly via competitive exclusion of native seedlings, and provides implications for recovery management efforts

CRISPR Deletion of a SVA Retrotransposon Demonstrates Function as a cis-Regulatory Element at the TRPV1/TRPV3 Intergenic Region

SINE-VNTR-Alu (SVA) retrotransposons are a subclass of transposable elements (TEs) that exist only in primate genomes. TE insertions can be co-opted as cis-regulatory elements (CREs); however, the regulatory potential of SVAs has predominantly been demonstrated using bioinformatic approaches and reporter gene assays. The objective of this study was to demonstrate SVA cis-regulatory activity by CRISPR (clustered regularly interspaced short palindromic repeats) deletion and subsequent measurement of direct effects on local gene expression. We identified a region on chromosome 17 that was enriched with human-specific SVAs. Comparative gene expression analysis at this region revealed co-expression of TRPV1 and TRPV3 in multiple human tissues, which was not observed in mouse, highlighting key regulatory differences between the two species. Furthermore, the intergenic region between TRPV1 and TRPV3 coding sequences contained a human specific SVA insertion located upstream of the TRPV3 promoter and downstream of the 3′ end of TRPV1, highlighting this SVA as a candidate to study its potential cis-regulatory activity on both genes. Firstly, we generated SVA reporter gene constructs and demonstrated their transcriptional regulatory activity in HEK293 cells. We then devised a dual-targeting CRISPR strategy to facilitate the deletion of this entire SVA sequence and generated edited HEK293 clonal cell lines containing homozygous and heterozygous SVA deletions. In edited homozygous ∆SVA clones, we observed a significant decrease in both TRPV1 and TRPV3 mRNA expression, compared to unedited HEK293. In addition, we also observed an increase in the variability of mRNA expression levels in heterozygous ∆SVA clones. Overall, in edited HEK293 with SVA deletions, we observed a disruption to the co-expression of TRPV1 and TRPV3. Here we provide an example of a human specific SVA with cis-regulatory activity in situ, supporting the role of SVA retrotransposons as contributors to species-specific gene expression