Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice

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

Published: Jan. 8, 2024

Abstract Compulsive behaviors are observed in a range of psychiatric disorders, however the neural substrates underlying not clearly defined. Here we show that basolateral amygdala-dorsomedial striatum (BLA-DMS) circuit activation leads to manifestation compulsive-like behaviors. We revealed BLA neurons projecting DMS, mainly onto dopamine D1 receptor-expressing neurons, largely overlap with neuronal population responds aversive predator stress, widely used anxiogenic stressor. Specific optogenetic BLA-DMS induced strong anxiety response followed by compulsive grooming. Furthermore, developed mouse model for compulsivity displaying wide spectrum chronically activating circuit. In these mice, persistent molecular changes at synapses were causally related phenotypes. Together, our study demonstrates involvement emergence enduring via its synaptic changes.

Language: Английский

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Transcriptional and anatomical diversity of medium spiny neurons in the primate striatum

Current Biology, Journal Year: 2021, Volume and Issue: 31(24), P. 5473 - 5486.e6

Published: Nov. 1, 2021

Language: Английский

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Striosomes and Matrisomes: Scaffolds for Dynamic Coupling of Volition and Action

Annual Review of Neuroscience, Journal Year: 2023, Volume and Issue: 46(1), P. 359 - 380

Published: April 18, 2023

Striosomes form neurochemically specialized compartments of the striatum embedded in a large matrix made up modules called matrisomes. Striosome-matrix architecture is multiplexed with canonical direct-indirect organization striatum. Striosomal functions remain to be fully clarified, but key information emerging. First, striosomes powerfully innervate nigral dopamine-containing neurons and can completely shut down their activity, following rebound excitation. Second, receive limbic cognition-related corticostriatal afferents are dynamically modulated relation value-based actions. Third, spatially interspersed among matrisomes interneurons influenced by local global neuromodulatory oscillatory activities. Fourth, tune engagement motivation perform reinforcement learning, manifest stereotypical behaviors, navigate valence conflicts discriminations. We suggest that, at an algorithmic level, could serve as distributed scaffolds provide formats striatal computations generated through development refined learning. propose that affect subjective states. By transforming corticothalamic other inputs functional striatum, they implement state transitions nigro-striato-nigral circuits bodily cognitive actions according internal motives whose compromised neuropsychiatric conditions.

Language: Английский

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Striosomes control dopamine via dual pathways paralleling canonical basal ganglia circuits

Current Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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Multiplexed action-outcome representation by striatal striosome-matrix compartments detected with a mouse cost-benefit foraging task

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: March 22, 2022

Abstract Learning about positive and negative outcomes of actions is crucial for survival underpinned by conserved circuits including the striatum. How associations between are formed not fully understood, particularly when have mixed features. We developed a novel foraging (‘bandit’) task requiring mice to maximize rewards while minimizing punishments. By 2-photon Ca ++ imaging, we monitored activity visually identified anterodorsal striatal striosomal matrix neurons. found that action-outcome reward punishment were encoded in parallel partially overlapping populations. Single neurons could, one action, encode opposing valence. Striosome compartments consistently exhibited stronger representations reinforcement than matrix, especially high or prediction errors. These findings demonstrate multiplexing contingencies single suggest important learning.

Language: Английский

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Excessive self-grooming, gene dysregulation and imbalance between the striosome and matrix compartments in the striatum of Shank3 mutant mice

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: March 16, 2023

Autism is characterized by atypical social communication and stereotyped behaviors. Mutations in the gene encoding synaptic scaffolding protein SHANK3 are detected 1–2% of patients with autism intellectual disability, but mechanisms underpinning symptoms remain largely unknown. Here, we behavior Shank3 Δ11/Δ11 mice from 3 to 12 months age. We observed decreased locomotor activity, increased self-grooming modification socio-sexual interaction compared wild-type littermates. then used RNAseq on four brain regions same animals identify differentially expressed genes (DEGs). DEGs were identified mainly striatum associated transmission (e.g., Grm2, Dlgap1 ), G-protein-signaling pathways Gnal , Prkcg1 Camk2g as well excitation/inhibition balance Gad2 ). Downregulated upregulated enriched clusters medium-sized spiny neurons expressing dopamine 1 (D1-MSN) 2 receptor (D2-MSN), respectively. Several ( Cnr1 Drd4 ) reported striosome markers. By studying distribution glutamate decarboxylase GAD65, encoded showed that compartment was enlarged displayed much higher expression GAD65 mice. Altogether, these results indicate altered -deficient strongly suggest, for first time, excessive related an imbalance striatal matrix compartments.

Language: Английский

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Striosomes Target Nigral Dopamine-Containing Neurons via Direct-D1 and Indirect-D2 Pathways Paralleling Classic Direct-Indirect Basal Ganglia Systems

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Balanced activity of canonical direct D1 and indirect D2 basal ganglia pathways is considered a core requirement for normal movement, their imbalance an etiologic factor in movement neuropsychiatric disorders. We present evidence conceptually equivalent pair direct-D1 indirect-D2 that arise from striatal projection neurons (SPNs) the striosome compartment rather than SPNs matrix, as do pathways. These S-D1 S-D2 striosomal target substantia nigra dopamine-containing instead motor output nuclei. They modulate oppositely to modulation by pathways: inhibitory excitatory. The circuits likely influence motivation learning action, complementing reorienting pathway modulation. A major conceptual reformulation classic direct-indirect model function needed, well reconsideration effects D2-targeting therapeutic drugs.

Language: Английский

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From Progenitors to Progeny: Shaping Striatal Circuit Development and Function

Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(46), P. 9483 - 9502

Published: Nov. 17, 2021

Understanding how neurons of the striatum are formed and integrate into complex synaptic circuits is essential to provide insight striatal function in health disease. In this review, we summarize our current understanding development associated with a focus on their embryonic origin. Specifically, address role distinct types progenitors, found proliferative zones ganglionic eminences ventral telencephalon, generation diverse interneurons projection neurons. Indeed, recent evidence would suggest that progenitor origin dictates key characteristics postnatal cells, including neurochemical content, location within striatum, long-range inputs. We also observations regarding progenitors cortical other regions discuss might inform future research eminences. Last, examine dysfunction can alter formation, as exemplified Huntington's disease autism spectrum disorder, increased have significant implications for directions improved therapeutic options. SIGNIFICANCE STATEMENT This review highlights recently defined novel roles cells shaping functional properties both striatum. It outlines developmental mechanisms guide neuronal from progeny Where questions remain open, cortex present possible avenues research. progenitor-centric perspective onto disorder. investigations manipulations clinical settings will likely require careful consideration great intrinsic diversity neurogenic potential.

Language: Английский

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Patchy Striatonigral Neurons Modulate Locomotor Vigor in Response to Environmental Valence

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Abstract Spiny projection neurons (SPNs) in the dorsal striatum play crucial roles locomotion control and value-based decision-making. SPNs, which include both direct-pathway striatonigral indirect-pathway striatopallidal neurons, can be further classified into subtypes based on distinct transcriptomic profiles cell body distribution patterns. However, how these SPN regulate spontaneous context of environmental valence remains unclear. Using Sepw1 - Cre transgenic mice, label a specific subtype characterized by patchy bodies striatum, we found that constrain motor vigor response to differentials. In modified light/dark box test, mice exhibited differential walking speeds between light dark zones. Genetic ablation SPNs disrupted restful slowing zone increased transition frequencies vivo recordings linked activity occupancy, speed, deceleration, with role mediating deceleration. Furthermore, chemogenetic activation SPNs—and optical particular—reduced attenuated speed-based discrimination. These findings reveal regulates implicit speed selection innate

Language: Английский

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Striatal function scrutinized through the PAN-TAN-FSI triumvirate

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: March 25, 2025

Understanding the information encoded by distinct components of neuronal circuitry in striatum represents an avenue for elucidating role this subcortical region adaptive behavior and its dysfunction pathological conditions. In behaving animals, conventional single neuron recordings generally differentiated between three main electrophysiologically identified subtypes striatum, referred to as phasically active neurons (PANs), tonically (TANs), fast-spiking interneurons (FSIs), assumed correspond GABAergic spiny projection neurons, cholinergic interneurons, parvalbumin-containing respectively. Considerable research has been devoted exploring behavior-related activities classified into PANs, TANs, FSIs animals engaged task performance, mostly monkeys. Although precise identification remains a major challenge, such electrophysiological studies have provided insights functional properties presumed striatal populations. review, we will focus on current ideas about functions subserved these subtypes, emphasizing their link specific aspects behaviors. We also underline issues that are yet be resolved regarding classification subgroups which emphasize importance considering potential overlap among characteristics molecular diversity types striatum.

Language: Английский

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