Dataset Information

Cholinergic control of striatal GABAergic microcircuits.

ABSTRACT: Cholinergic interneurons (CINs) are essential elements of striatal circuits and functions. Although acetylcholine signaling via muscarinic receptors (mAChRs) has been well studied, more recent data indicate that postsynaptic nicotinic receptors (nAChRs) located on striatal GABAergic interneurons (GINs) are equally critical. One example is that CIN stimulation induces large disynaptic inhibition of striatal projection neurons (SPNs) mediated by nAChR activation of GINs. Although these circuits are ideally positioned to modulate striatal output, the neurons involved are not definitively identified because of an incomplete mapping of CINs-GINs interconnections. Here, we show that CINs modulate four GINs populations via an intricate mechanism involving co-activation of presynaptic and postsynaptic mAChRs and nAChRs. Using optogenetics, we demonstrate the participation of tyrosine hydroxylase-expressing GINs in the disynaptic inhibition of SPNs via heterotypic electrical coupling with neurogliaform interneurons. Altogether, our results highlight the importance of CINs in regulating GINs microcircuits via complex synaptic/heterosynaptic mechanisms.

SUBMITTER: Kocaturk S

PROVIDER: S-EPMC9648160 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cholinergic control of striatal GABAergic microcircuits.

Kocaturk Samet S Guven Elif Beyza EB Shah Fulva F Tepper James M JM Assous Maxime M

Cell reports 20221001 4

Cholinergic interneurons (CINs) are essential elements of striatal circuits and functions. Although acetylcholine signaling via muscarinic receptors (mAChRs) has been well studied, more recent data indicate that postsynaptic nicotinic receptors (nAChRs) located on striatal GABAergic interneurons (GINs) are equally critical. One example is that CIN stimulation induces large disynaptic inhibition of striatal projection neurons (SPNs) mediated by nAChR activation of GINs. Although these circuits ar ...[more]

PMID: 36288709

Similar Datasets

Project description:Striatal oscillatory activity is associated with movement, reward, and decision-making, and observed in several interacting frequency bands. Local field potential recordings in rodent striatum show dopamine- and reward-dependent transitions between two states: a "spontaneous" state involving ? (?15-30 Hz) and low ? (?40-60 Hz), and a state involving ? (?4-8 Hz) and high ? (?60-100 Hz) in response to dopaminergic agonism and reward. The mechanisms underlying these rhythmic dynamics, their interactions, and their functional consequences are not well understood. In this paper, we propose a biophysical model of striatal microcircuits that comprehensively describes the generation and interaction of these rhythms, as well as their modulation by dopamine. Building on previous modeling and experimental work suggesting that striatal projection neurons (SPNs) are capable of generating ? oscillations, we show that networks of striatal fast-spiking interneurons (FSIs) are capable of generating ?/? (ie, 2 to 6 Hz) and ? rhythms. Under simulated low dopaminergic tone our model FSI network produces low ? band oscillations, while under high dopaminergic tone the FSI network produces high ? band activity nested within a ?/? oscillation. SPN networks produce ? rhythms in both conditions, but under high dopaminergic tone, this ? oscillation is interrupted by ?/?-periodic bursts of ?-frequency FSI inhibition. Thus, in the high dopamine state, packets of FSI ? and SPN ? alternate at a ?/? timescale. In addition to a mechanistic explanation for previously observed rhythmic interactions and transitions, our model suggests a hypothesis as to how the relationship between dopamine and rhythmicity impacts motor function. We hypothesize that high dopamine-induced periodic FSI ?-rhythmic inhibition enables switching between ?-rhythmic SPN cell assemblies representing the currently active motor program, and thus that dopamine facilitates movement in part by allowing for rapid, periodic shifts in motor program execution.

Dataset Information

Cholinergic control of striatal GABAergic microcircuits.

Publications

Cholinergic control of striatal GABAergic microcircuits.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets