Biology subjects

Janssen, W. G.

Publications and source records attributed to Janssen, W. G..

3 recordsLinked to original sources

bioRxiv2024

Deep brain stimulation induces white matter remodeling and functional changes to brain-wide networks

Deep brain stimulation (DBS) is an emerging therapeutic option for treatment resistant neurological and psychiatric disorders, most notably depression. Despite this, little is known about the anatomical and functional mechanisms that underlie this therapy. Here we targeted stimulation to the white matter adjacent to the subcallosal anterior cingulate cortex (SCC-DBS) in macaques, modeling the location in the brain proven effective for depression. We demonstrate that SCC-DBS has a selective effect on white matter macro- and micro-structure in the cingulum bundle distant to where stimulation was delivered. SCC-DBS also decreased functional connectivity between subcallosal and posterior cingulate cortex, two areas linked by the cingulum bundle and implicated in depression. Our data reveal that white matter remodeling as well as functional effects contribute to DBSs therapeutic efficacy.

neuroscience↗

bioRxiv2023

High-throughput sequencing of macaque basolateral amygdala projections reveals dissociable connectional motifs with frontal cortex

The basolateral amygdala (BLA) projects widely across the macaque frontal cortex1-4, and amygdalo-frontal projections are critical for optimal emotional responding5 and decision- making6. Yet, little is known about the single-neuron architecture of these projections: namely, whether single BLA neurons project to multiple parts of the frontal cortex. Here, we use MAPseq7 to determine the projection patterns of over 3000 macaque BLA neurons. We found that one-third of BLA neurons have two or more distinct targets in parts of frontal cortex and of subcortical structures. Further, we reveal non-random structure within these branching patterns such that neurons with four targets are more frequently observed than those with two or three, indicative of widespread networks. Consequently, these multi-target single neurons form distinct networks within medial and ventral frontal cortex consistent with their known functions in regulating mood and decision-making. Additionally, we show that branching patterns of single neurons shape functional networks in the brain as assessed by fMRI-based functional connectivity. These results provide a neuroanatomical basis for the role of the BLA in coordinating brain-wide responses to valent stimuli8 and highlight the importance of high- resolution neuroanatomical data for understanding functional networks in the brain.

neuroscience↗

bioRxiv2018

Quantitative analysis of synaptic pathology and neuroinflammation: an initial study in a female rhesus monkey model of the “synaptic” phase of Alzheimer’s disease

BackgroundSoluble oligomers of the A{beta} peptide (A{beta}Os) are toxins that target and disrupt synapses. Generation of A{beta}Os has been recently recognized as a probable initiating event in Alzheimers disease (AD), leading to cognitive impairment. There is a translational gap in AD studies, with promising drugs developed based on work in rodent models failing in AD patients in clinical trials. Additionally, although women have a two-fold greater lifetime risk of developing AD compared to men, females have not been a focus of preclinical studies. Thus, we sought to develop a model of A{beta}O toxicity in female rhesus monkeys, to take advantage of the more highly differentiated cortical structure in this species as well as the similarities in the endocrine system between rhesus monkeys and humans.\n\nMethodsRepeated intracerebroventricular (i.c.v) injections of A{beta}Os were performed in adult female rhesus monkeys. Controls were unoperated aged matched monkeys. High-resolution confocal microscopy and morphometric analysis of Alexa 568 (A568) filled neurons were used to evaluate synaptic, neuronal, and glial markers in the dorsolateral prefrontal cortex (dlPFC) and hippocampus after A{beta}O injections. Cerebrospinal fluid (CSF) and brain tissue were also collected and analyzed for biomarkers of AD pathology, including: phosphorylated Tau protein (pTau), total Tau, A{beta}1-42, A{beta}1-40 and TNF- levels.\n\nResultsHere, we report that A{beta}O injection into the lateral ventricle of the brain induces loss of 37% of thin spines in targeted dlPFC neurons, an area highly vulnerable in AD and aging. Further, A{beta}Os associate with the synaptic marker PSD95, inducing loss of more than 60% of local excitatory synapses. A{beta}Os induce a robust neuroinflammatory response in the hippocampus, far from the injection site, with numerous activated ameboid microglia and TNF- release. Finally, A{beta}Os increased CSF levels of A{beta}1-42, pTau Ser396 and pTau Ser199, but not A{beta}1-40 or total Tau.\n\nConclusionsThese initial findings from detailed quantitative analysis of effects of A{beta}O administration on synapses in a female nonhuman primate model are a very promising step toward understanding the mechanism of early AD pathogenesis in the primate brain, and may help develop an effective disease-modifying therapy of high relevance to womens health.

neuroscience↗