Claustrum and dorsal endopiriform cortex complex cell-identity is determined by Nurr1 and regulates hallucinogenic-like states in mice

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 18, 2024

Abstract The Claustrum/dorsal endopiriform cortex complex (CLA) is an enigmatic brain region with extensive glutamatergic projections to multiple cortical areas. transcription factor Nurr1 highly expressed in the CLA, but its role this not understood. By using conditional gene-targeted mice, we show that a crucial regulator of CLA neuron identity. Although neurons remain intact absence Nurr1, distinctive gene expression pattern abolished. has been hypothesized control hallucinations, little known how responds hallucinogens. After deletion both hallucinogen receptor and signaling are lost. Furthermore, functional ultrasound Neuropixel electrophysiological recordings revealed hallucinogenic-receptor agonists’ effects on connectivity between prefrontal sensorimotor cortices altered Nurr1-ablated mice. Our findings suggest Nurr1-targeted strategies provide additional avenues for studies CLA.

Language: Английский

---

Network models to enhance the translational impact of cross-species studies

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(9), P. 575 - 588

Published: July 31, 2023

Language: Английский

---

Distinct neurochemical influences on fMRI response polarity in the striatum

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 21, 2023

Summary The striatum is the primary input nucleus of basal ganglia, widely studied for its complex roles in health and disease. Functional magnetic resonance imaging (fMRI) studies are essential discerning striatal function, however relationship between neuronal hemodynamic activity, critical interpreting fMRI signals, has not been rigorously examined striatum. We find that optogenetic stimulation neurons or afferents evokes negative responses rats can occur despite broad increases local activity. Intra-striatal pharmacological manipulations suggest opioidergic, but dopaminergic transmission contributes to signals (the latter instead associated with positive signals). Striatal activity peaks also behaving rats. Negative observed human under conditions anticipated increases. Our results prompt consideration cellular neurochemical environments along signal interpretation.

Language: Английский

---

Acute alcohol induces greater dose-dependent increase in the lateral cortical network functional connectivity in adult than adolescent rats

Addiction Neuroscience, Journal Year: 2023, Volume and Issue: 7, P. 100105 - 100105

Published: June 2, 2023

Alcohol misuse and, particularly adolescent drinking, is a major public health concern. While evidence suggests that alcohol use affects frontal brain regions are important for cognitive control over behavior little known about how acute exposure alters large-scale networks and sex age may moderate such effects. Here, we employ recently developed functional magnetic resonance imaging (fMRI) protocol to acquire rat connectivity data an established analytical pipeline examine the effect of sex, age, dose on within between three rodent networks: defaul mode, salience, lateral cortical network. We identify intra- inter-network differences establish moderation models reveal significant influences alcohol-induced network connectivity. Through this work, make brain-wide isotropic fMRI with challenge publicly available, hope facilitate future discovery regions/circuits causally relevant impact use.

Language: Английский

---

Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Aug. 1, 2023

Exposure to an acute stressor triggers a complex cascade of neurochemical events in the brain. However, deciphering their individual impact on stress-induced molecular changes remains major challenge. Here, we combine RNA sequencing with selective pharmacological, chemogenetic, and optogenetic manipulations isolate contribution locus coeruleus-noradrenaline (LC-NA) system stress response mice. We reveal that NA release during exposure regulates large reproducible set genes dorsal ventral hippocampus via β-adrenergic receptors. For smaller subset these genes, show triggered by LC stimulation is sufficient mimic transcriptional response. observe effects both sexes, independent pattern frequency activation. Using retrograde approach, demonstrate hippocampus-projecting neurons directly regulate hippocampal gene expression. Overall, highly astrocyte-enriched emerges as key targets LC-NA activation, most prominently several subunits protein phosphatase 1 (Ppp1r3c, Ppp1r3d, Ppp1r3g) type II iodothyronine deiodinase (Dio2). These results highlight importance astrocytic energy metabolism thyroid hormone signaling LC-mediated function offer new for understanding how impacts brain health disease.

Language: Английский

---