Local and afferent synaptic pathways in the striatal microcircuitry

Silberberg, Gilad; Bolam, J. Paul

doi:10.1016/j.conb.2015.05.002

Cited by 103 publications

(89 citation statements)

References 62 publications

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“…The influence of the diverse locally projecting interneurons in behavior and disease is less clear compared to the better-characterized principal neurons, the spiny projection neurons (SPNs, also known as medium spiny neurons) (Silberberg and Bolam, 2015, Tepper et al., 2010). Modern molecular tools are increasingly used to pinpoint a cell type-specific contribution to striatal-related disease (Girasole et al., 2018, Rapanelli et al., 2017, Skene et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

Diversity of Interneurons in the Dorsal Striatum Revealed by Single-Cell RNA Sequencing and PatchSeq

et al. 2018

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SummaryStriatal locally projecting neurons, or interneurons, act on nearby circuits and shape functional output to the rest of the basal ganglia. We performed single-cell RNA sequencing of striatal cells enriching for interneurons. We find seven discrete interneuron types, six of which are GABAergic. In addition to providing specific markers for the populations previously described, including those expressing Sst/Npy, Th, Npy without Sst, and Chat, we identify two small populations of cells expressing Cck with or without Vip. Surprisingly, the Pvalb-expressing cells do not constitute a discrete cluster but rather are part of a larger group of cells expressing Pthlh with a spatial gradient of Pvalb expression. Using PatchSeq, we show that Pthlh cells exhibit a continuum of electrophysiological properties correlated with expression of Pvalb. Furthermore, we find significant molecular differences that correlate with differences in electrophysiological properties between Pvalb-expressing cells of the striatum and those of the cortex.

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Section: Introductionmentioning

confidence: 99%

Diversity of Interneurons in the Dorsal Striatum Revealed by Single-Cell RNA Sequencing and PatchSeq

et al. 2018

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“…The central components of the striatal circuit are cortical glutamatergic terminals that activate striatal projection neurons (medium spiny neurons, MSN). Glutamatergic signaling is modulated by dopamine from DA SNpc cells in concert with the activity of local cholinergic interneurons (ACh) and fast‐spiking GABAergic interneurons (FS; Threlfell et al, 2010; Bonsi et al, 2011; Surmeier, Carrillo‐Reid, & Bargas, 2011; Silberberg & Bolam, 2015) that together constitute the striatal modulatory circuit. The relevance of these neuronal populations on striatal function is highlighted by the alteration of distinct neuronal types in several neurological disorders, including chorea (MSN), parkinsonism (DA SNpc), Tourette syndrome (ACh and FS), and dystonia (ACh).…”

Section: Introductionmentioning

confidence: 99%

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Sanchez-Garcia

Nieto-González

García-Junco-Clemente

et al. 2018

Aging Cell

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The striatum integrates motor behavior using a well‐defined microcircuit whose individual components are independently affected in several neurological diseases. The glial cell line‐derived neurotrophic factor (GDNF), synthesized by striatal interneurons, and Sonic hedgehog (Shh), produced by the dopaminergic neurons of the substantia nigra (DA SNpc), are both involved in the nigrostriatal maintenance but the reciprocal neurotrophic relationships among these neurons are only partially understood. To define the postnatal neurotrophic connections among fast‐spiking GABAergic interneurons (FS), cholinergic interneurons (ACh), and DA SNpc, we used a genetically induced mouse model of postnatal DA SNpc neurodegeneration and separately eliminated Smoothened (Smo), the obligatory transducer of Shh signaling, in striatal interneurons. We show that FS postnatal survival relies on DA SNpc and is independent of Shh signaling. On the contrary, Shh signaling but not dopaminergic striatal innervation is required to maintain ACh in the postnatal striatum. ACh are required for DA SNpc survival in a GDNF‐independent manner. These data demonstrate the existence of three parallel but interdependent neurotrophic relationships between SN and striatal interneurons, partially defined by Shh and GDNF. The definition of these new neurotrophic interactions opens the search for new molecules involved in the striatal modulatory circuit maintenance with potential therapeutic value.

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“…Most input to the striatum is glutamatergic. Importantly, the striatum also receives dopaminergic input from the substantia nigra and ventral tegmental area [58,59]. Striatal dopamine innervation plays a role in striatal plasticity [60].…”

Section: Discussionmentioning

confidence: 99%

“…As noted above, glutamate is the main neurotransmitter input to the striatum; in particular, striatal input from cortex uses glutamate as its main neurotransmitter [59]. Synaptic zinc binding level has strong ties to the glutamatergic system and can modulate all three kinds of glutamate receptors [64,56].…”

Section: Discussionmentioning

confidence: 99%

Assessment of Biometal Profile in Children with Autism Spectrum Disorder, with Attention Deficit Hyperactivity Disorder, or with Other Psychiatric Diagnoses: A Comparative Outpatient Study

Pakyürek¹,

Azarang²,

Iosif³

et al. 2018

Acta Psychopathol

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Background: In recent years, the impact of various micronutrients on the symptoms of ADHD and ASD has been studied. Our study was aimed at evaluating the association between the level of serum magnesium, zinc and ferritin in children diagnosed with ADHD and/or ASD. Methods:This case-control pilot study consisted of 32 children who met DSM-V criteria for ADHD, 15 children who met DSM-V criteria for ASD and 12 age-matched control children from Electronic Medical Record database. Serum magnesium, zinc and ferritin values were com-pared with ANOVA.Results: Blood ferritin level was found to be significantly lower in affected groups (F=5.9, p=0.0056). A trend towards decreased values of plasma zinc level was also found in affected children (F=2.25, p=0.12); whereas no suggestion of any difference in blood magnesium levels between three groups was significant. Non-parametric analyses were also run and the p value for ferritin 0.08, showed weaker evidence of significance. Conclusions:Results of this study indicated that low level of blood ferritin may be a risk factor for development of ASD and ADHD. Future investigations with larger controlled trials are needed and correlational studies would also be helpful.

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Local and afferent synaptic pathways in the striatal microcircuitry

Cited by 103 publications

References 62 publications

Diversity of Interneurons in the Dorsal Striatum Revealed by Single-Cell RNA Sequencing and PatchSeq

Diversity of Interneurons in the Dorsal Striatum Revealed by Single-Cell RNA Sequencing and PatchSeq

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

Assessment of Biometal Profile in Children with Autism Spectrum Disorder, with Attention Deficit Hyperactivity Disorder, or with Other Psychiatric Diagnoses: A Comparative Outpatient Study

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