GABAergic circuits mediate the reinforcement-related signals of striatal cholinergic interneurons

English, Daniel F.; Ibáñez-Sandoval, Osvaldo; Stark, Eran; Tecuapetla, Fatuel; Buzsáki, György; Deisseroth, Karl; Tepper, James M.; Koós, Tibor

doi:10.1038/nn.2984

Cited by 260 publications

(361 citation statements)

References 50 publications

(79 reference statements)

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“…The majority of GABAergic interneurons in the striatum are parvalbumin-positive FS interneurons, which project primarily to the MSNs. Although FS interneurons are excited by nicotinic agonists (51), optogenetic activation of SChIs failed to increase FS interneuron spiking in one study (52). Additionally, optogenetic stimulation of SChIs in ChAT-ChR2 mice elicits both fast and slow inhibitory postsynaptic potentials in MSNs by nicotinic-mediated GABA release from dopamine projections to striatum (53) and neuropeptide Y-expressing neurogliaform GABAergic interneurons, resulting in inhibition of MSNs (52).…”

Section: M1 Superficialmentioning

confidence: 99%

“…Although FS interneurons are excited by nicotinic agonists (51), optogenetic activation of SChIs failed to increase FS interneuron spiking in one study (52). Additionally, optogenetic stimulation of SChIs in ChAT-ChR2 mice elicits both fast and slow inhibitory postsynaptic potentials in MSNs by nicotinic-mediated GABA release from dopamine projections to striatum (53) and neuropeptide Y-expressing neurogliaform GABAergic interneurons, resulting in inhibition of MSNs (52). However, nicotinic receptors generally quickly desensitize and, thus, we did not expect GABAergic blockade of MSN spiking to continue through the 5 s of stimulation used in our current study.…”

Section: M1 Superficialmentioning

confidence: 99%

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Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Kondabolu

Roberts

Bucklin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cortico-basal ganglia-thalamic (CBT) neural circuits are critical modulators of cognitive and motor function. When compromised, these circuits contribute to neurological and psychiatric disorders, such as Parkinson's disease (PD). In PD, motor deficits correlate with the emergence of exaggerated beta frequency (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) oscillations throughout the CBT network. However, little is known about how specific cell types within individual CBT brain regions support the generation, propagation, and interaction of oscillatory dynamics throughout the CBT circuit or how specific oscillatory dynamics are related to motor function. Here, we investigated the role of striatal cholinergic interneurons (SChIs) in generating beta and gamma oscillations in cortical-striatal circuits and in influencing movement behavior. We found that selective stimulation of SChIs via optogenetics in normal mice robustly and reversibly amplified beta and gamma oscillations that are supported by distinct mechanisms within striatal-cortical circuits. Whereas beta oscillations are supported robustly in the striatum and all layers of primary motor cortex (M1) through a muscarinic-receptor mediated mechanism, gamma oscillations are largely restricted to the striatum and the deeper layers of M1. Finally, SChI activation led to parkinsonianlike motor deficits in otherwise normal mice. These results highlight the important role of striatal cholinergic interneurons in supporting oscillations in the CBT network that are closely related to movement and parkinsonian motor symptoms.E xaggerated beta oscillations (15-30 Hz) within the cortico-basal ganglia-thalamic (CBT) neural network are putative electrophysiological correlates of bradykinesia and rigidity in Parkinson's disease (PD) (1-4). Therapies that effectively manage PD motor symptoms, such as dopamine replacement therapy and deep brain stimulation, are associated with a suppression of the exaggerated beta oscillations (4, 5). Beta oscillations are also found in the CBT circuits of patients with other movement-related disorders, such as epilepsy and dystonia (6, 7), and in normal, nonhuman primates (8, 9) and normal rodents (10, 11). Moreover, brief elevations (≤200 ms) of beta oscillations are observed in the basal ganglia of task-performing nonhuman primates and rodents during specific phases of behavioral tasks (10, 12, 13), indicating that beta oscillations may be important for motor and nonmotor functions. In contrast to the regulated temporal variability of beta oscillations in normal motor functions, temporal stability is correlated with the parkinsonian motor symptoms of bradykinesia and rigidity (2). Together, these findings suggest that brief epochs of beta oscillations are a normal aspect of basal ganglia dynamics, their temporal modulation is important for movement regulation, and loss of regulation or uncontrolled expression of beta oscillations may contribute to movement deficits, such as those observed in PD.Despite the clear link bet...

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Section: M1 Superficialmentioning

confidence: 99%

Section: M1 Superficialmentioning

confidence: 99%

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Kondabolu

Roberts

Bucklin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…ACh was shown to depolarize FSIs directly through nAChRs and attenuate their GABAergic inhibition on MSNs by presynaptic muscarinic acetylcholine receptors (mAChR) on FSI terminals (Koos and Tepper 2002). More recently, a study showed that activation of a novel inhibitory NPY-neurogliaform by nicotinic synaptic inputs from cholinergic interneurons contributes to slow inhibitory currents in MSNs (English et al 2011). …”

Section: Modulation Of Interneurons and Msns By Acetylcholinementioning

confidence: 99%

Functional roles of neurotransmitters and neuromodulators in the dorsal striatum

Kim

Bakes

et al. 2012

Learn. Mem.

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The dorsal striatum, with its functional microcircuits galore, serves as the primary gateway of the basal ganglia and is known to play a key role in implicit learning. Initially, excitatory inputs from the cortex and thalamus arrive on the direct and indirect pathways, where the precise flow of information is then regulated by local GABAergic interneurons. The balance of excitatory and inhibitory transmission in the dorsal striatum is modulated by neuromodulators such as dopamine and acetylcholine. Under pathophysiological states in the dorsal striatum, an alteration in excitatory and inhibitory transmission may underlie dysfunctional motor control. Here, we review the cellular connections and modulation of striatal microcircuits and propose that modulating the excitatory and inhibitory balance in synaptic transmission of the dorsal striatum is important for regulating locomotion.The dorsal striatum is best known for its role in decision-making, especially in action selection and initiation through the convergence of sensorimotor, cognitive, and motivational information (DeLong 1990;Smith et al. 1998;Balleine et al. 2007). As the primary input of the basal ganglia, the striatum receives glutamatergic inputs from the cortex and thalamus and in turn projects GABAergic outputs to the globus pallidus and substantia nigra pars reticulata (SNr). Inputs from the cortex and thalamus both form excitatory synaptic connections on medium spiny neurons (MSN) in which cortical afferents are from the sensory, motor, and associational cortex (Bolam et al. 2000), and thalamic afferents are from the intralaminar thalamic nuclei (Doig et al. 2010). These glutamatergic inputs are then processed in the dorsal striatum where numerous connections between various types of neurons exist. Thus, the complexity of neuronal circuits has made it difficult to elucidate the functional roles of the striatum. Recently, studies focused on interneurons that reside in the dorsal striatum have characterized the physiological features and functional connections. For example, parvalbumin-expressing fastspiking interneurons (PV-FSI) and neuropeptide-Y positive lowthreshold spiking interneurons (NPY-LTS) form synaptic connections with MSNs and regulate the firing activity of the principal neuron MSNs (Koos and Tepper 1999;Gittis et al. 2010;Chuhma et al. 2011). These interneurons were shown to have distinct firing patterns and connections, and thus they may exert different effects on MSNs. Other crucial connections are the cholinergic, dopaminergic, and serotonergic axons that strongly innervate the dorsal striatum. These projections are essential for modulating striatal circuits and disruption of such signaling can result in movement impairments and neurological disorders such as Huntington's disease (Lovinger 2010). This review summarizes recent reports of the microcircuits present in the dorsal striatum, although serotonergic signaling is excluded, and suggests a putative role for striatal microcircuits in motor dysfunction and/or hyperactivity that ...

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“…Neurons within the NAc comprises a majority (B95%) of medium spiny neurons (MSNs) and heterogeneous populations of interneurons, including fast-spiking interneurons (FSIs), GABAergic interneurons, and cholinergic interneurons, which provide functional feedforward inhibition to MSN populations (English et al, 2012;Gage et al, 2010;Koos and Tepper, 1999). These neuronal groups are important for rewarding and aversive motivational processing.…”

Section: Introductionmentioning

confidence: 99%

Dopamine Receptor Blockade Modulates the Rewarding and Aversive Properties of Nicotine via Dissociable Neuronal Activity Patterns in the Nucleus Accumbens

Sun

Laviolette

2014

Neuropsychopharmacol

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The mesolimbic pathway comprising the ventral tegmental area (VTA) and projection terminals in the nucleus accumbens (NAc) has been identified as a critical neural system involved in processing both the rewarding and aversive behavioral effects of nicotine. Transmission through dopamine (DA) receptors functionally modulates these effects directly within the NAc. Nevertheless, the neuronal mechanisms within the NAc responsible for these bivalent behavioral effects are presently not known. Using an unbiased conditioned place preference procedure combined with in vivo neuronal recordings, we examined the effects of nicotine reward and aversion conditioning on intra-NAc neuronal sub-population activity patterns. We report that intra-VTA doses of nicotine that differentially produce rewarding or aversive behavioral effects produce opposite effects on sub-populations of fast-spiking interneurons (FSIs) or medium spiny neurons (MSNs) within the shell region of the NAc (NAshell). Thus, while the rewarding effects of intra-VTA nicotine were associated with inhibition of FSI and activation of MSNs, the aversive effects of nicotine produced the opposite pattern of NAshell neuronal population activity. Blockade of DA transmission with a broad-spectrum DA receptor antagonist, a-flupenthixol, strongly inhibited the spontaneous activity of NAshell FSIs, and reversed the conditioning properties of intra-VTA nicotine, switching nicotineconditioned responses from aversive to rewarding. Remarkably, DA receptor blockade switched intra-NAshell neuronal population activity from an aversion to a reward pattern, concomitant with the observed switch in behavioral conditioning effects.

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GABAergic circuits mediate the reinforcement-related signals of striatal cholinergic interneurons

Cited by 260 publications

References 50 publications

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Functional roles of neurotransmitters and neuromodulators in the dorsal striatum

Dopamine Receptor Blockade Modulates the Rewarding and Aversive Properties of Nicotine via Dissociable Neuronal Activity Patterns in the Nucleus Accumbens

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