GABAergic interneurons expressing the α2 nicotinic receptor subunit are functionally integrated in the striatal microcircuit

Tokarska, Anna; Silberberg, Gilad

doi:10.1016/j.celrep.2022.110842

Cited by 12 publications

(5 citation statements)

References 104 publications

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“…There are three families of ionotropic receptors with intrinsic cation permeable channels. These are N‐methyl‐D‐aspartate (NMDA), alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA), and kainate receptors 41–43 . Glutamatergic system is a potential therapeutic target for amnesia, anxiety, hyperalgesia, and psychosis, including schizophrenia 44–47 .…”

Section: Discussionmentioning

confidence: 99%

“…These are N‐methyl‐D‐aspartate (NMDA), alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA), and kainate receptors. 41 , 42 , 43 Glutamatergic system is a potential therapeutic target for amnesia, anxiety, hyperalgesia, and psychosis, including schizophrenia. 44 , 45 , 46 , 47 The symptoms of these diseases have several common features with METH dependence; therefore, similar mechanisms may be caused by DNA methylation in METH dependence.…”

Section: Discussionmentioning

confidence: 99%

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Epigenome‐wide association study on methamphetamine dependence

Shirai,

Okazaki,

Tanifuji

et al. 2024

Addiction Biology

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Repeated abuse of methamphetamine (METH) can cause dependence, repeated relapse of psychotic symptoms, compulsive drug‐seeking behaviour, and various neurological symptoms. These long‐term biological changes may be associated with epigenetic mechanisms; however, the association between METH use and epigenetic mechanisms has been poorly investigated. Thus, we performed an epigenome‐wide association study of METH dependence using genomic DNA extracted from the blood samples of 24 patients with METH dependence and 24 normal controls. All participants were of Japanese descent. We tested the association between METH dependence and DNA methylation using linear regression analysis. We found epigenome‐wide significant associations at four CpG sites, one of which occurred in the CNOT1 gene and another in the PUM1 gene. We especially noted the CNOT1 and PUM1 genes as well as several other genes that indicated some degree of association with METH dependence. Among the relatively enriched Gene Ontology terms, we were interested in terms of mRNA metabolism, respirasome, and excitatory extracellular ligand‐gated ion channel activity. Among the relatively enriched Kyoto Encyclopedia of Genes and Genome pathways, we noted pathways of several neurological diseases. Our results indicate that genetic changes akin to those in other psychiatric or neurodegenerative disorders may also occur via epigenetic mechanisms in patients with METH dependence.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epigenome‐wide association study on methamphetamine dependence

Shirai,

Okazaki,

Tanifuji

et al. 2024

Addiction Biology

View full text Add to dashboard Cite

show abstract

“…1-1) (Kawaguchi, 1993 & 1997; Tepper et al, 2018). While most parvalbumin interneurons in the striatum are FSIs, there are likely regional subtypes of FSIs with distinct responses and connectivity to cortical brain regions (Monteiro et al, 2018; Tokarska & Silberberg, 2022). Future experiments could use further genetic cell typing, which could help clarify the variability we observed between individual cells.…”

Section: Discussionmentioning

confidence: 99%

Cell-Type Specific Connectivity of Whisker-Related Sensory and Motor Cortical Input to Dorsal Striatum

Sanabria

Baskar

Yonk

et al. 2023

Preprint

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The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and is considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in the strength of their connections with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS, and as a result exert an opposing influence on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution onto striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1, and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex-vivo patch-clamp electrophysiology. We found that SPNs are less innervated by S1 compared to M1, but FSIs receive a similar number of inputs from both M1 and S1. In addition, M1 and S1 inputs were distributed similarly across the proximal, medial, and distal regions of SPNs and FSIs. Notably, clusters of inputs were prevalent in SPNs but not FSIs. Our results suggest that SPNs have stronger functional connectivity to M1 compared to S1 due to a higher density of synaptic inputs. The clustering of M1 and S1 inputs onto SPNs but not FSIs suggest that cortical inputs are integrated through cell-type specific mechanisms and more generally have implications for how sensorimotor integration is performed in the striatum.

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“…1 G , 5 G ) instead of the possibility that the ML position or the location of a patched neuron within the M1/S1 projection field biased innervation patterns towards M1 or S1. Importantly, recent evidence suggests that there are subtypes of parvalbumin-positive FSIs in the striatum with distinct physiological properties and connectivity to cortical brain regions ( Muñoz-Manchado et al, 2018 ; Monteiro et al, 2018 ; Tokarska and Silberberg, 2022 ). In addition, due to the lack of spines, which can compartmentalize a synaptic input to specific areas of the membrane, the integration properties of FSIs may be less dependent on the number and location of inputs but rather on the intrinsic properties of the FSI, such as the distribution of ion channels and receptors along the dendrites ( Cornford et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Cell-Type Specific Connectivity of Whisker-Related Sensory and Motor Cortical Input to Dorsal Striatum

Sanabria,

Baskar,

Yonk

et al. 2023

eNeuro

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The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in their connection strength with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS, and as a result exert distinct influences on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution onto striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1 in male and female mice, and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex-vivo patch-clamp electrophysiology. We found that M1 and S1 dually innervate SPNs and FSIs, however there is a consistent bias towards the M1 input in SPNs that is not found in FSIs. In addition, M1 and S1 inputs were distributed similarly across the proximal, medial, and distal regions of SPN and FSI dendrites. Notably, closely localized M1 and S1 clusters of inputs were more prevalent in SPNs than FSIs, suggesting that cortical inputs are integrated through cell-type specific mechanisms. Our results suggest that the stronger functional connectivity from M1 to SPNs compared to S1, as previously observed, is due to a higher quantity of synaptic inputs. Our results have implications for how sensorimotor integration is performed in the striatum through cell-specific differences in corticostriatal connections.Significance StatementThe dorsolateral striatum (DLS) is a key brain area involved in sensorimotor integration due to its dense innervation by the primary motor (M1) and sensory cortex (S1). However, the quantity and anatomical distribution of these inputs to the striatal cell population has not been well characterized. In this study we demonstrate that corticostriatal projections from M1 and S1 differentially innervate spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS. S1 inputs innervate SPNs less than M1 and are likely to form synaptic clusters in SPNs but not in FSIs. These findings suggest that sensorimotor integration is partly achieved by differences in the synaptic organization of corticostriatal inputs to local striatal microcircuits.

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GABAergic interneurons expressing the α2 nicotinic receptor subunit are functionally integrated in the striatal microcircuit

Cited by 12 publications

References 104 publications

Epigenome‐wide association study on methamphetamine dependence

Epigenome‐wide association study on methamphetamine dependence

Cell-Type Specific Connectivity of Whisker-Related Sensory and Motor Cortical Input to Dorsal Striatum

Cell-Type Specific Connectivity of Whisker-Related Sensory and Motor Cortical Input to Dorsal Striatum

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