iScience, Journal Year: 2024, Volume and Issue: 27(10), P. 110886 - 110886
Published: Sept. 4, 2024
Language: Английский
Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(12), P. 2237 - 2249
Published: Oct. 26, 2023
Abstract The amygdala is a brain region primarily associated with emotional response. use of genetic markers and single-cell transcriptomics can provide insights into behavior-associated cell state changes. Here we present detailed cell-type taxonomy the adult mouse during fear learning memory consolidation. We perform RNA sequencing on naïve fear-conditioned mice, identify 130 neuronal types validate their spatial distributions. A subset all transcriptionally responsive to retrieval. activated engram cells upregulate activity-response genes coordinate expression neurite outgrowth, synaptic signaling, plasticity development. known previously undescribed candidate learning. Our molecular atlas may be used generate hypotheses unveil neuron neural circuits regulating component memory.
Language: Английский
Citations
57
Nature, Journal Year: 2024, Volume and Issue: 630(8015), P. 141 - 148
Published: May 22, 2024
Abstract Fentanyl is a powerful painkiller that elicits euphoria and positive reinforcement 1 . also leads to dependence, defined by the aversive withdrawal syndrome, which fuels negative 2,3 (that is, individuals retake drug avoid withdrawal). Positive maintain opioid consumption, addiction in one-fourth of users, largest fraction for all addictive drugs 4 Among receptors, µ-opioid receptors have key role 5 , yet induction loci circuit adaptations eventually lead remain unknown. Here we injected mice with fentanyl acutely inhibit γ-aminobutyric acid-expressing neurons ventral tegmental area (VTA), causing disinhibition dopamine neurons, increased nucleus accumbens. Knockdown VTA abolished transients reinforcement, but remained unchanged. We identified expressing central amygdala (CeA) whose activity was enhanced during withdrawal. CeA eliminated symptoms, suggesting they mediate reinforcement. Thus, optogenetic stimulation caused place aversion, readily learned press lever pause express receptors. Our study parses neuronal populations trigger CeA, respectively. lay out organization develop interventions reducing facilitating rehabilitation.
Language: Английский
Citations
18
Nature, Journal Year: 2023, Volume and Issue: 616(7957), P. 510 - 519
Published: April 5, 2023
Language: Английский
Citations
39
Nature, Journal Year: 2025, Volume and Issue: unknown
Published: April 2, 2025
Animals learn the value of foods on basis their postingestive effects and thereby develop aversions to that are toxic1-10 preferences those nutritious11-13. However, it remains unclear how brain is able assign credit flavours experienced during a meal with feedback signals can arise after substantial delay. Here we reveal an unexpected role for reactivation neural flavour representations in this temporal credit-assignment process. To begin, leverage fact mice associate novel14,15, but not familiar, delayed gastrointestinal malaise investigate represents support aversive learning. Analyses brain-wide activation patterns network amygdala regions unique being preferentially activated by novel across every stage learning (consumption, memory retrieval). By combining high-density recordings optogenetic stimulation malaise-coding hindbrain neurons, show selectively reactivate from recent meal. The degree malaise-driven individual neurons predicts strengthening responses upon retrieval, which turn leads stabilization population-level representation recently consumed flavour. contrast, degrade absence consequences. Thus, demonstrate plasticity may feedback.
Language: Английский
Citations
2
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Feb. 20, 2024
ABSTRACT The lateral septum (LS) is a nucleus in the ventral forebrain that modulates complex social and affective behaviors. Several distinct neuronal types have been described LS; however, full extent of this cellular molecular diversity remains unclear. We address gap by profiling transcriptional identity mature LS neurons originating from two progenitor lineages defined their anatomical location expression transcription factor Nkx2.1 . describe 12 molecularly subtypes fall into main groups: those with history without. discovered lineage share an enrichment select cell adhesion communication molecules. Despite this, we found developmental origins can exhibit significant similarities. then examined spatial relationships among LS, revealing each subtype occupies discrete domain. These domains are graded patterns gene correlate taxonomy neuron encode proteins involved synaptic signaling. Lastly, genetically labeled non-overlapping subgroups neurons, detailed connective, morphological, electrophysiological properties. Our findings offer deeper understanding heterogeneity paving way for future studies how these contribute to regulating emotional motivated
Language: Английский
Citations
7
Science Advances, Journal Year: 2023, Volume and Issue: 9(3)
Published: Jan. 18, 2023
Memory encoding and retrieval rely on specific interactions across multiple brain areas. Although connections between individual areas have been extensively studied, the anatomical functional specificity of neuronal circuit organization underlying information transfer remains unclear. Here, we combine transsynaptic viral tracing, optogenetic manipulations, calcium dynamics recordings to dissect multisynaptic connectivity amygdala. We identify a distinct basolateral amygdala (BLA) subpopulation that connects disynaptically periaqueductal gray (PAG) via central (CeA). This disynaptic pathway serves as core element necessary for learning expression conditioned fear exhibits learning-related plasticity. Together, our findings demonstrate utility approaches analysis indicate may be general feature organization.
Language: Английский
Citations
16
Science Advances, Journal Year: 2023, Volume and Issue: 9(21)
Published: May 24, 2023
The central amygdala (CeA) consists of numerous genetically defined inhibitory neurons that control defensive and appetitive behaviors including feeding. Transcriptomic signatures cell types their links to function remain poorly understood. Using single-nucleus RNA sequencing, we describe nine CeA clusters, which four are mostly associated with two aversive behaviors. To analyze the activation mechanism neurons, characterized serotonin receptor 2a (Htr2a)-expressing (CeAHtr2a) comprise three clusters were previously shown promote In vivo calcium imaging revealed CeAHtr2a activated by fasting, hormone ghrelin, presence food. Moreover, these required for orexigenic effects ghrelin. Appetitive responsive fasting ghrelin project parabrachial nucleus (PBN) causing inhibition target PBN neurons. These results illustrate how transcriptomic diversification relates hormone-regulated feeding behavior.
Language: Английский
Citations
16
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Feb. 13, 2024
The basolateral amygdala (BLA) is essential for assigning positive or negative valence to sensory stimuli. Noxious stimuli that cause pain are encoded by an ensemble of
Language: Английский
Citations
6
Cell Reports, Journal Year: 2024, Volume and Issue: 43(9), P. 114669 - 114669
Published: Aug. 23, 2024
Maladaptive plasticity is linked to the chronification of diseases such as pain, but transition from acute chronic pain not well understood mechanistically. Neuroplasticity in central nucleus amygdala (CeA) has emerged a mechanism for sensory and emotional-affective aspects injury-induced although evidence comes studies conducted almost exclusively conditions agnostic cell type specificity. Here, we report time-dependent changes genetically distinct projection-specific CeA neurons neuropathic pain. Hyperexcitability CRF projection synaptic parabrachial (PB) input at stage shifted hyperexcitability without non-CRF phase. Accordingly, chemogenetic inhibition PB→CeA pathway mitigated pain-related behaviors acute, chronic, Cell-type-specific temporal neuroplasticity provide neurobiological clinical observation that simply prolonged persistence
Language: Английский
Citations
6
Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: Sept. 13, 2023
With concurrent global epidemics of chronic pain and opioid use disorders, there is a critical need to identify, target manipulate specific cell populations expressing the mu-opioid receptor (MOR). However, available tools transgenic models for gaining long-term genetic access MOR+ neural types circuits involved in modulating pain, analgesia addiction across species are limited. To address this, we developed catalog MOR promoter (MORp) based constructs packaged into adeno-associated viral vectors that drive transgene expression cells. MORp designed from regions upstream mouse Oprm1 gene (mMORp) were validated transduction efficiency selectivity endogenous neurons brain, spinal cord, periphery mice, with additional studies revealing robust rats, shrews, human induced pluripotent stem (iPSC)-derived nociceptors. The mMORp vivo fiber photometry, behavioral chemogenetics, intersectional strategies also demonstrated. Lastly, (hMORp) efficiently transduced macaque cortical OPRM1+ Together, our toolkit provides researchers type functionally mu-opioidergic range vertebrate translational addiction, neuropsychiatric disorders.
Language: Английский
Citations
12