Neurology, Journal Year: 2025, Volume and Issue: 104(10)
Published: May 6, 2025
Language: Английский
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
Citations
19
Frontiers in Neural Circuits, Journal Year: 2021, Volume and Issue: 15
Published: March 2, 2021
The globus pallidus externa (GPe) functions as a central hub in the basal ganglia for processing motor and non-motor information through creation of complex connections with other nuclei brain regions. Recently, adoption sophisticated genetic tools, substantial advances have been made understanding distinct molecular, anatomical, electrophysiological, functional properties GPe neurons non-neuronal cells. Impairments dopamine transmission contribute to Parkinson's disease (PD), most common movement disorder that severely affects patients' life quality. Altered neuron activity synaptic also found both PD patients pre-clinical models. In this review, we will summarize main findings on composition, connectivity functionality different cell populations potential GPe-related mechanisms symptoms better understand type circuit-specific roles normal conditions.
Language: Английский
Citations
65
Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)
Published: June 17, 2022
Abstract Endocannabinoid (eCB), 2 -arachidonoyl-glycerol (2-AG), the most abundant eCB in brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations 2-AG synthase diacylglycerol lipase β ( DAGLB ) to an early onset autosomal recessive Parkinsonism. is main human and mouse substantia nigra (SN) dopaminergic neurons (DANs). In mice, SN levels were markedly correlated with motor performance during locomotor skill acquisition. Genetic knockdown of Daglb nigral DANs substantially reduced impaired learning, particularly across-session learning. Conversely, pharmacological inhibition degradation increased levels, DAN activity dopamine release rescued learning deficits. Together, demonstrate that -deficiency contributes pathogenesis Parkinsonism, reveal importance DAGLB-mediated biosynthesis regulating neuronal release, suggest potential benefits augmentation alleviating
Language: Английский
Citations
39
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
Citations
27
Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(7), P. 1147 - 1159
Published: June 19, 2023
Language: Английский
Citations
26
npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)
Published: Jan. 29, 2025
Abstract The motor symptoms of Parkinson’s Disease are attributed to the degeneration dopamine neurons in substantia nigra pars compacta (SNc). Previous work MCI-Park mouse model has suggested that loss somatodendritic transmission predicts development deficits. In current study, brain slices from mice were used investigate signaling SNc prior and through onset movement Electrophysiological properties impaired by p30 somatic volume was decreased at all time points. D2 receptor activated potassium evoked quinpirole present initially, but declined after p30. contrast, D2-IPSCs absent decrease GPCR-mediated inhibition met with increased spontaneous GABA A signaling. Dendro-dendritic synapses identified as an early locus dysfunction response bioenergetic decline suggest dendritic release sites may contribute induction degeneration.
Language: Английский
Citations
1
Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Citations
1
Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(18), P. 4036 - 4059
Published: March 17, 2021
We have previously established that PV + neurons and Npas1 are distinct neuron classes in the external globus pallidus (GPe): they different topographical, electrophysiological, circuit, functional properties. Aside from Foxp2 neurons, which a unique subclass within class, we lack driver lines effectively capture other GPe subclasses. In this study, examined utility of Kcng4-Cre, Npr3-Cre, Npy2r-Cre mouse (both males females) for delineation subtypes. By using these novel lines, provided most exhaustive investigation electrophysiological studies subtypes to date. Corroborating our prior studies, can be divided into two statistically clusters map onto classes. combining optogenetics machine learning-based tracking, showed optogenetic perturbation generated behavioral structures. Our findings further highlighted dissociable roles regulating movement anxiety-like behavior. concluded Npr3 Kcng4 subclasses respectively. Finally, by examining local collateral connectivity, inferred circuit mechanisms involved motor patterns observed with perturbations. summary, identifying allow manipulations subtypes, created new opportunities interrogations cellular substrates important function dysfunction. SIGNIFICANCE STATEMENT Within basal ganglia, (GPe) has long been recognized its involvement control. However, lacked an understanding precisely how is controlled at level as result complexity. transgenic cell-specific approaches, genetically-defined patterns. addition, vivo contributions part shaped local, inhibitory connections GPe. sum, foundation future investigations disease pathophysiology.
Language: Английский
Citations
52
Cell Reports, Journal Year: 2022, Volume and Issue: 40(7), P. 111228 - 111228
Published: Aug. 1, 2022
The basal ganglia operate largely in closed parallel loops, including an associative circuit for goal-directed behavior originating from the dorsomedial striatum (DMS) and a somatosensory important habit formation dorsolateral (DLS). An exception to this organization has been proposed explain how information might be transferred between striatal subregions, example, DMS DLS during formation. "ascending spiral hypothesis" proposes that disinhibits dopamine signaling through tri-synaptic, open-loop striatonigrostriatal circuit. Here, we use transsynaptic intersectional genetic tools investigate both closed- circuits. We find strong evidence which would allow subregions regulate their own release. also functional synapses open loops. However, these are unable modulate tonic neuron firing, questioning prominence of role mediating crosstalk subregions.
Language: Английский
Citations
37
Current Biology, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 1, 2024
Language: Английский
Citations
6