Cholinergic control of striatal GABAergic microcircuits

Kocatürk, Samet; Guven, Elif Beyza; Shah, Fulva; Tepper, James M.; Assous, Maxime

doi:10.1016/j.celrep.2022.111531

Cited by 20 publications

(20 citation statements)

References 73 publications

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“…In the other branch of our classification, we find the two populations representing the most abundant interneuron classes: PTHLH and TAC3, together with the well-described and scarce cholinergic cells (CHAT), which have already been thoroughly characterized in the literature 3,25,46,47 . Both PTHLH and TAC3 populations further split into two subclasses of unequal proportions: PTHLH and PTHLH/MOXD1, and TAC3 and TAC3/SEMA3A, respectively.…”

Section: Discussionmentioning

confidence: 82%

“…Among the genes with ion channel activity, we found GRID1 (glutamate ionotropic receptor), SCN7A (sodium voltage-gated channel), and CACNA2D3 (Calcium Voltagegated channel). Interestingly, when comparing functional genes in human vs. mouse striatum 20 , we found that the mouse interneuron Th cell class had been previously described to express nicotinic receptors, including those responding to a3b4 (a specific subtype) 47,52,53 . This mouse Th population is characterized by the expression of Tac2 (homologous of the human TAC3 gene coding for a tachykinin precursor) and also by the expression of Trh, which is one of the best markers for Th cells in mouse.…”

Section: Interneuron Diversity In the Human Striatum Is Higher Than E...mentioning

confidence: 95%

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Interneuron diversity in the human dorsal striatum

Garma

Harder

Barba-Reyes

et al. 2023

Preprint

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Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangle the complex neurological and psychiatric diseases affecting this brain structure. We performed single-nucleus RNA-sequencing (snRNA-seq) of postmortem human caudate nucleus (CN) and putamen (Pu) samples to elucidate the diversity and abundance of interneuron populations and their transcriptional structure in the human dorsal striatum. We propose a new taxonomy of striatal interneurons with eight main classes. We provide specific markers for all subclasses and validated some of them with quantitative in situ fluorescence hybridization, such as a novel PTHLH-expressing population that exhibits different abundance and gene expression between CN and Pu. For the most abundant interneuron populations in human striatum, PTHLH and TAC3, we found matching known mouse interneuron populations based on key functional genes such as ion channels and synaptic receptors. Remarkably, human TAC3 and mouse Th populations share important similarities including the expression of the neuropeptide tachykinin 3. Finally, we were able to integrate our dataset with several prior smaller human striatal snRNA-seq studies, thus supporting the generalizability of this new harmonized taxonomy.

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Section: Discussionmentioning

confidence: 82%

Section: Interneuron Diversity In the Human Striatum Is Higher Than E...mentioning

confidence: 95%

Interneuron diversity in the human dorsal striatum

Garma

Harder

Barba-Reyes

et al. 2023

Preprint

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“…Working through nicotinic acetylcholine receptors (nAChRs), ChIs can activate both neurogliaform interneurons (NGFIs) and tyrosine hydroxylase interneurons (THIs) giving rise to GABAAR-mediated currents in SPNs [20]. To monitor evoked responses in SPNs, perforated patch recordings were made from identified iSPNs or dSPNs using the approach described above.…”

Section: Gabaar Engagement Depolarized Spns In the Down-statementioning

confidence: 99%

State-dependent GABAergic regulation of striatal spiny projection neuron excitability

Day¹,

Belal²,

Surmeier³

et al. 2023

Preprint

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Synaptic transmission mediated by GABAA receptors (GABAARs) in adult, principal striatal spiny projection neurons (SPNs) can suppress ongoing spiking, but its effect on synaptic integration at sub-threshold membrane potentials is less well characterized, particularly those near the resting down-state. To fill this gap, a combination of molecular, optogenetic, optical and electrophysiological approaches were used to study SPNs in mouse ex vivo brain slices, and computational tools were used to model somatodendritic synaptic integration. Activation of GABAARs, either by uncaging of GABA or by optogenetic stimulation of GABAergic synapses, evoked currents with a reversal potential near -60 mV in perforated patch recordings from both juvenile and adult SPNs. Molecular profiling of SPNs suggested that this relatively positive reversal potential was not attributable to NKCC1 expression, but rather to a dynamic equilibrium between KCC2 and Cl-/HCO3- cotransporters. Regardless, from down-state potentials, optogenetic activation of dendritic GABAergic synapses depolarized SPNs. This GABAAR-mediated depolarization summed with trailing ionotropic glutamate receptor (iGluR) stimulation, promoting dendritic spikes and increasing somatic depolarization. Simulations revealed that a diffuse dendritic GABAergic input to SPNs effectively enhanced the response to coincident glutamatergic input. Taken together, our results demonstrate that GABAARs can work in concert with iGluRs to excite adult SPNs when they are in the resting down-state, suggesting that their inhibitory role is limited to brief periods near spike threshold. This state-dependence calls for a reformulation of the role intrastriatal GABAergic circuits.

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“…Our finding of impaired glutamate transmission in male LBN mice opens the possibility of an imbalance between excitatory and inhibitory transmission in the dorsal striatum. MSNs in the dorsal striatum receive GABAergic inputs from local GABAergic interneurons and adjacent MSNs (Taverna et al, 2004 ; Kocaturk et al, 2022 ). Additionally, recent work has shown that glycine receptors containing the α2 subunit are critical for regulating excitability of striatal MSNs by controlling tonic inhibition (Molchanova et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Early life adversity impaired dorsal striatal synaptic transmission and behavioral adaptability to appropriate action selection in a sex-dependent manner

Carvalho

Khoja

Haile

et al. 2023

Front. Synaptic Neurosci.

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Early life adversity (ELA) is a major health burden in the United States, with 62% of adults reporting at least one adverse childhood experience. These experiences during critical stages of brain development can perturb the development of neural circuits that mediate sensory cue processing and behavioral regulation. Recent studies have reported that ELA impaired the maturation of dendritic spines on neurons in the dorsolateral striatum (DLS) but not in the dorsomedial striatum (DMS). The DMS and DLS are part of two distinct corticostriatal circuits that have been extensively implicated in behavioral flexibility by regulating and integrating action selection with the reward value of those actions. To date, no studies have investigated the multifaceted effects of ELA on aspects of behavioral flexibility that require alternating between different action selection strategies or higher-order cognitive processes, and the underlying synaptic transmission in corticostriatal circuitries. To address this, we employed whole-cell patch-clamp electrophysiology to assess the effects of ELA on synaptic transmission in the DMS and DLS. We also investigated the effects of ELA on the ability to update action control in response to outcome devaluation in an instrumental learning paradigm and reversal of action-outcome contingency in a water T-maze paradigm. At the circuit level, ELA decreased corticostriatal glutamate transmission in male but not in female mice. Interestingly, in DMS, glutamate transmission is decreased in male ELA mice, but increased in female ELA mice. ELA impaired the ability to update action control in response to reward devaluation in a context that promotes goal-directedness in male mice and induced deficits in reversal learning. Overall, our findings demonstrate the sex- and region-dependent effects of ELA on behavioral flexibility and underlying corticostriatal glutamate transmission. By establishing a link between ELA and circuit mechanisms underlying behavioral flexibility, our findings will begin to identify novel molecular mechanisms that can represent strategies for treating behavioral inflexibility in individuals who experienced early life traumatic incidents.

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Cholinergic control of striatal GABAergic microcircuits

Cited by 20 publications

References 73 publications

Interneuron diversity in the human dorsal striatum

Interneuron diversity in the human dorsal striatum

State-dependent GABAergic regulation of striatal spiny projection neuron excitability

Early life adversity impaired dorsal striatal synaptic transmission and behavioral adaptability to appropriate action selection in a sex-dependent manner

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