Biology subjects

Chieng, B.

Publications and source records attributed to Chieng, B..

7 recordsLinked to original sources

bioRxiv2026

Silencing basal forebrain cholinergic input to the infralimbic cortex renders fear extinction resistant to renewal

The infralimbic cortex (IL) is critical for the extinction of conditioned fear and receives dense cholinergic innervation from the basal forebrain, particularly from the horizontal limb of the diagonal band of Broca (HDB). Acetylcholine release in the IL regulates fear-related processes, but the mechanisms involved remain poorly understood. We investigated whether cholinergic projections from the HDB to the IL regulate the formation, extinction, and renewal of fear memories. Using optogenetics in male and female transgenic rats, we silenced the HDB to IL cholinergic pathway during either fear conditioning or extinction. Silencing during fear conditioning had no effect, whereas silencing during extinction enhanced extinction retrieval and prevented fear renewal. These effects were anatomically specific, as silencing the neighboring HDB to prelimbic cortex pathway had no such consequence. In ex vivo IL slices, stimulation of HDB cholinergic terminals preferentially excited interneurons over pyramidal neurons, consistent with feedforward inhibition of IL output. Finally, blockade of IL nicotinic acetylcholine receptors during extinction fully reproduced the effects of silencing the pathway, whereas muscarinic blockade attenuated renewal without affecting extinction retrieval. These findings indicate that cholinergic input from the HDB to the IL controls the acquisition and contextual specificity of extinction and identify nicotinic signaling in the IL as a potential target for improving extinction-based therapies.

neuroscience↗

bioRxiv2025

Backward Conditioning Reveals Flexibility in Infralimbic Cortex Inhibitory Memories

While the infralimbic cortex (IL) is recognized as critical for behavioral inhibition, the content of the inhibitory memories stored in this region remains elusive. To probe this content, we examined some of the conditions that allow retrieval and facilitation of an inhibitory memory stored in the IL using optogenetic stimulation in female and male rats. We found that IL stimulation did not facilitate an initial fear extinction session. However, prior experience with fear extinction enabled IL stimulation to facilitate subsequent fear extinction. Importantly, the facilitative effects of IL stimulation were not limited to fear extinction experience, as prior exposure to backward fear conditioning also enabled IL stimulation to enhance later fear extinction. The effects were stimulus-specific and did not depend on the motivational context present during the prior experience, as backward appetitive conditioning allowed IL stimulation to facilitate later fear extinction. Additional experiments ruled out stimulus familiarity as an explanation for the facilitative effects of IL stimulation and demonstrated that IL-mediated facilitations occur in procedures other than fear extinction. Together, these findings demonstrate that the IL stores inhibitory memories that are extremely flexible since they can be retrieved and used across many inhibitory procedures and distinct motivational contexts. These features establish the IL as a critical hub for the flexible application of inhibitory knowledge that allows adaptive responses in dynamic environments.

neuroscience↗

bioRxiv2025

The influence of nucleus accumbens shell D1 and D2 neurons on outcome-specific Pavlovian instrumental transfer

The nucleus accumbens shell (NAc-S) and its projections to the ventral pallidum (VP) are thought to be critical for stimulus-based decisions. The NAc-S is predominantly composed of spiny projection neurons (SPNs) that express either the dopamine D1 (D1-SPNs) or the dopamine D2 receptor (D2-SPNs). Yet, the role of these two neuronal subpopulations and their inputs to the VP in stimulus-based decisions remains unknown. Here, we used optogenetics in female and male knock-in rats to selectively silence D1-or D2-SPNs and their projections to the VP at a time when the rats were required to use predictive stimuli to choose between two instrumental actions. Silencing either population of NAc-S SPNs disrupted choice. Silencing NAc-S D1-SPNs terminals in the VP also disrupted choice. However, choice was left intact by silencing NAc-S D2-SPNs terminals in the VP. Together, these findings provide novel insights into the cellular mechanisms and circuitry underlying stimulus-based decisions. We discuss how these insights are consistent with a recent model proposing that these decisions are controlled by an opioid-based memory system residing in the NAc-S.

neuroscience↗

bioRxiv2024

Context-Seq: CRISPR-Cas9 Targeted Nanopore Sequencing for Transmission Dynamics of Antimicrobial Resistance

Precisely understanding how and to what extent antimicrobial resistance (AMR) is exchanged between animals and humans is needed to inform control strategies. Metagenomic sequencing has low detection for rare targets such as antibiotic resistance genes, while whole genome sequencing of isolates misses exchange between uncultured bacterial species. We introduce Context-Seq, CRISPR-Cas9 targeted sequencing of ARGs and their genomic context with long-reads. Using Context-Seq, we investigate genetically similar AMR elements containing the ARGs blaCTX-M and blaTEM between adults, children, poultry, and dogs in Nairobi, Kenya. We identify genetically distinct clusters containing blaTEM and blaCTX-M that are shared between animals and humans within and between households. We also uncover potentially pathogenic hosts of ARGs including Escherichia coli, Klebsiella pneumonia, and Haemophilus influenzae in this study context. Context-Seq complements conventional methods to obtain an additional view of bacterial and mammalian hosts in the proliferation of AMR.

microbiology↗

bioRxiv2022

Cognitive effects of thalamostriatal degeneration are ameliorated by normalizing striatal cholinergic activity

The loss of neurons in parafascicular thalamus (Pf) and of their inputs to dorsomedial striatum (DMS) are associated with Lewy body disease (LBD) and Parkinsons disease dementia (PDD) and have been linked to the effects of neuroinflammation. In rats, these inputs regulate the function of striatal cholinergic interneurons (CINs) that are necessary for the flexible encoding of the action-outcome (AO) associations for goal-directed action. We found that these inputs modify the encoding, not retrieval, of new AO associations and cause burst-pause firing of CINs in the DMS during AO remapping. These adaptive effects were abolished by neuroinflammation in the Pf, resulting in the loss of goal-directed control when the rats were required to update AO associations after a change in contingency. We found that the neuronal and behavioral deficits induced by inflammation in the Pf were rescued by administration of selegiline, a MAO-B inhibitor that we found also enhances ATPase activity in CINs, suggesting a potential treatment for cognitive deficits associated with inflammation affecting the function of midline thalamic nuclei and related structures.

neuroscience↗

bioRxiv2020

Striatal direct and indirect pathway neurons differentially control the encoding and updating of goal-directed learning.

The posterior dorsomedial striatum (pDMS) is necessary for goal-directed action, however the role of the direct (dSPN) and indirect (iSPN) spiny projection neurons in the pDMS in such action remains unclear. In this series of experiments, we examined the role of pDMS SPNs in goal-directed action and found that, whereas dSPNs were critical for goal-directed learning and for energizing the learned response, iSPNs were involved in updating that learning to support response flexibility. Instrumental training elevated expression of the plasticity marker Zif268 in dSPNs only, and chemogenetic suppression of dSPN activity during training prevented goal-directed learning. Unilateral optogenetic inhibition of dSPNs induced an ipsilateral response bias in goal-directed action performance. In contrast, although initial goal-directed learning was unaffected by iSPN manipulations, optogenetic inhibition of iSPNs, but not dSPNs, impaired the updating of this learning and attenuated response flexibility after changes in the action-outcome contingency.

neuroscience↗

bioRxiv2018

Integrating water, sanitation, handwashing, and nutrition interventions to reduce child soil-transmitted helminth and Giardia infections: a cluster-randomized controlled trial in rural Kenya

Background.Helminth and protozoan infections affect >1 billion children globally. Improved water, sanitation, handwashing, and nutrition could be more sustainable control strategies for parasite infections than mass drug administration (MDA), while providing other quality of life benefits.\n\nMethods and Findings.We enrolled geographic clusters of pregnant women into a cluster-randomized controlled trial that tested six interventions: disinfecting drinking water(W), improved sanitation(S), handwashing with soap(H), combined WSH, improved nutrition(N), and combined WSHN. We assessed intervention effects on parasite infections by measuring Ascaris lumbricoides, Trichuris trichiura, hookworm, and Giardia duodenalis among individual children born to enrolled mothers and their older siblings (ClinicalTrials.gov NCT01704105). We collected stool specimens from 9077 total children in 622 clusters, including 2346 children in control, 1117 in water, 1160 in sanitation, 1141 in handwashing, 1064 in WSH, 1072 in nutrition, and 1177 in WSHN. In the control group, 23% of children were infected with Ascaris lumbricoides, 1% with Trichuris trichuria, 2% with hookworm and 39% with Giardia duodenalis. After two years of intervention exposure, Ascaris infection prevalence was 18% lower in the water treatment arm (95% confidence interval (CI) 0%, 33%), 22% lower in the WSH arm (CI 4%, 37%), and 22% lower in the WSHN arm (CI 4%, 36%) compared to control. Individual sanitation, handwashing, and nutrition did not significantly reduce Ascaris infection on their own, and integrating nutrition with WSH did not provide additional benefit. Trichuris and hookworm were rarely detected, resulting in imprecise effect estimates. No intervention reduced Giardia. Reanalysis of stool samples by quantitative polymerase chain reaction (qPCR) confirmed the reductions in Ascaris infections measured by microscopy in the WSH and WSHN groups. Lab technicians and data analysts were blinded to treatment assignment, but participants and sample collectors were not blinded. The trial was funded by the Bill & Melinda Gates Foundation and USAID.\n\nConclusions.Our results suggest integration of improved water quality, sanitation, and handwashing could contribute to sustainable control strategies for Ascaris infections, particularly in similar settings with recent or ongoing deworming programs. Water treatment alone was similarly effective to integrated WSH, providing new evidence that drinking water should be given increased attention as a transmission pathway for Ascaris.

clinical trials↗