Cholinergic modulation of synaptic integration and dendritic excitability in the striatum.

paper Cited Public

Authors: Oldenburg, Ian Antón; Ding, Jun B
Year: 2011
Journal: Current opinion in neurobiology
PMID: 21550798
DOI: 10.1016/j.conb.2011.04.004
PMCID: PMC3138897

Figure 1

Muscarinic signaling affecting the integration of glutamatergic signaling in MSNsSchematic of a striatopallidal MSN dendrite and spine. Muscarinic receptor activation modulates glutamate release and intrinsic excitability of MSNs by altering the gating of Ca2+ and K+ channels.

LLM interpretation

This is a schematic diagram illustrating how muscarinic signaling modulates glutamatergic inputs in a striatopallidal medium spiny neuron (MSN) dendrite and spine. The figure depicts cortical and thalamic inputs releasing glutamate (Glu) to activate AMPA and NMDA receptors, while acetylcholine (ACh) acts on M1 and M2 muscarinic receptors. The diagram shows that M1 receptor activation inhibits various potassium channels (Kir2, Kv4.2, Kv7) and modulates calcium channels (Cav1.3), while M2 receptors are located on the presynaptic terminals of the glutamatergic inputs.

Figure 2

Interactions between M1 and CB1 signallingIn the striatal medium spiny neuron, M1 receptor activation promotes PLCβ1/DAGLα- mediated production of 2-AG to induce retrograde suppression of inhibitory synaptic transmission. At excitatory synapses, lowering ACh release reduces the activity of M1 muscarinic receptors, which leads to enhanced opening of Cav1.3 channels in response to synaptic depolarization. The elevated Ca2+ influx results in enhanced production of endocannabinoid and activation of presynaptic CB-1 receptors that reduce glutamate release, which is critical for LTD induction in the striatum. Abbreviations: PLC, phospholipase C; DAG, 1,2-diacylglycerol.

LLM interpretation

This is a schematic diagram illustrating the interactions between M1 muscarinic and CB1 receptor signaling in a striatal medium spiny neuron. The figure depicts two pathways: one where M1 receptor activation leads to PLC and DAG lipase activity to produce 2-AG, which acts on presynaptic CB1 receptors to suppress inhibitory GABAergic inputs (DSI). A second pathway shows how M1 receptor modulation affects Cav1.3 channels and calcium influx to trigger endocannabinoid production, which activates presynaptic CB1 receptors to reduce glutamate release at excitatory synapses, facilitating long-term depression (LTD).

Figure 3

Signal transduction pathways mediating the effects of muscarinic receptors in MSNsAbbreviations: ACh, acetylcholine; DA, dopamine; DAG, 1,2-diacylglycerol; M1R, Muscarinic M1 receptor; M2R, Muscarinic M2 receptor; IP3, inositol 1,4,5 trisphosphate; NMDAR, NMDA receptor; PKA, protein kinase A; PKC, protein kinase C; PLC, phospholipase C; PP-2B, protein phosphatase 2B; RCS, regulator of calmodulin signaling.

LLM interpretation

This is a signaling pathway diagram illustrating the muscarinic receptor signaling cascades in MSNs. It compares the M2-class receptor (M2/3/4R) pathway, which involves $G\alpha_i$ inhibition of adenylyl cyclase and cAMP, with the M1-class receptor (M1/5R) pathway, which activates $Gq/11$ and PLC. The M1-class pathway is shown triggering a complex cascade involving PIP2, IP3, DAG, and $Ca^{2+}$, ultimately modulating various ion channels including Cav, Kv7, Kir2.3, and NMDAR.

#	Section	Preview
20	Indirect modulation of inhibitory synaptic transmission by ACh	Taken together, ACh modulation of inhibition consists of two opposing components, simultaneously…
21	Concluding remarks	In the last few years, our understanding of the signaling mechanism controlling synaptic plasticity…
22	Concluding remarks	How a relatively sparse interneuron population, such as striatal cholinergic interneurons,…
23	Concluding remarks	These new approaches, in combination with conventional physiology and behavioral analysis should…

Name	Type
acetylcholine	drug
ACh	drug
AHP local	phenotype
associative learning	phenotype
attentional shifts local	phenotype
basal ganglia	anatomy
Behaving monkeys local	cohort
Ca2+	drug
CACNA1D local	gene
c-AMP local	drug
Cav1.3 channel local	drug
Cav2 channel local	drug
Cav2 channels local	drug
CB1 receptor	drug
Channelrhodopsin-2 local	drug
cholinergic agonists	drug
Cholinergic interneuron local	anatomy
Cholinergic interneurons local	drug
cholinergic neurons	phenotype
Cholinesterase local	drug
ChR2 transgenic mice local	cohort
Chrm1	gene
clozapine-N-oxide	drug
Cnr1	gene
cortex	anatomy
Corticostriatal circuits local	anatomy
Corticostriatal feed-forward inhibition local	phenotype
corticostriatal terminals local	anatomy
Cre	gene
Cre transgenic mice local	cohort
D1 receptor	drug
DA signaling local	drug
Dendritic excitability local	phenotype
dendritic integration local	phenotype
Dendritic membrane potential local	phenotype
Dendritic shaft local	phenotype
depolarization-induced suppression of inhibition	phenotype
dopamine	drug
Dopamine D2 receptor	drug
DREADDs local	drug
Dystonia local	phenotype
endocannabinoids	drug
endocannabinoid system	drug
Excitatory postsynaptic potentials local	phenotype
Excitatory synapse local	phenotype
Fast-spiking interneuron local	anatomy
Fast spiking interneurons local	cohort
firing	phenotype
GABA	phenotype
GABAA receptor	drug
GABAB receptor	drug
GABAergic IPSCs local	phenotype
Gi/o	drug
glutamate	drug
glutamatergic EPSCs local	phenotype
GNAQ local	gene
Gq/11 local	drug
Gβγ local	drug
Halorhodopsin local	drug
hippocampus	anatomy
hM3Dq	drug
hM4D local	drug
Homer1	gene
Huntington's disease	phenotype
Ih local	drug
Indirect pathway local	anatomy
Inhibitory synapse local	phenotype
intralaminar thalamic neurons local	anatomy
KCNJ local	gene
KCNJ2 local	gene
KCNJ4 local	gene
KCNQ	gene
Kir2.3 local	gene
Kir2 channel local	drug
Kv4 channel local	drug
Kv7 channel local	drug
M1 local	drug
M1 receptor local	drug
M2/3 receptors local	drug
M2-like receptors local	drug
M2 receptor	drug
M3 muscarinic receptor	drug
M4 local	drug
M4 receptor local	drug
M4 receptors local	drug
M5 local	drug
medium spiny neuron	anatomy
medium spiny neurons	anatomy
Medium spiny neurons local	cohort
mGluR2 local	drug
motor learning local	phenotype
Motor thalamus local	anatomy
MSN local	drug
MSNs	anatomy
Muscarinic acetylcholine receptor	drug
Muscarinic M1-like receptor local	drug
Muscarinic M2-like receptor local	drug
nicotinic acetylcholine receptor	drug
Nicotinic acetylcholine receptor local	gene
No-Go response local	phenotype
NPY	gene
Parkinson's disease	phenotype
Parvalbumin	gene
pertussis toxin	drug
phosphatase 2B local	drug
Phosphatidylinositol 4,5-bisphosphate local	drug
phospholipase C	drug
PIP2 local	drug
PKC	gene
Plcb1	gene
PLCβ local	drug
potassium channels	drug
presynaptic glutamatergic terminals local	anatomy
psychomotor disorder local	phenotype
Pvalb	gene
reward	phenotype
Shank	gene
Slc17a8	gene
slow afterhyperpolarization (sAHP) local	drug
sodium currents local	drug
Soma local	phenotype
Spiking local	phenotype
Spine local	phenotype
Sst	gene
Striatal MSNs local	anatomy
Striatal network local	anatomy
striatonigral MSN local	anatomy
Striatonigral MSN local	anatomy
striatonigral MSNs local	anatomy
striatonigral neurons local	anatomy
striatopallidal MSN local	anatomy
Striatopallidal MSN local	anatomy
striatopallidal MSNs local	anatomy
Striatopallidal MSNs local	anatomy
Striatopallidal neuron local	anatomy
striatopallidal neurons	anatomy
striatum	anatomy
synaptic plasticity	phenotype
TANs local	anatomy
thalamostriatal terminals local	anatomy
thalamus	anatomy

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Linking Cholinergic Interneurons, Synaptic Plasticity, and Behavior during the Extinction of a Cocaine-Context Association.	Lee J et al.	—	2016	→
A Biologically Inspired Computational Model of Basal Ganglia in Action Selection.	Baston C et al.	—	2015	→
Cholinergic interneurons in the dorsal and ventral striatum: anatomical and functional considerations in normal and diseased conditions.	Gonzales KK et al.	—	2015	→
KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons.	Pérez-Ramírez MB et al.	—	2015	→
Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt glomerular output.	Liu S et al.	—	2015	→
Role of the endogenous cannabinoid system in nicotine addiction: novel insights.	Gamaleddin IH et al.	—	2015	→
Differential cortical activation of the striatal direct and indirect pathway cells: reconciling the anatomical and optogenetic results by using a computational method.	Morita K	—	2014	→
M5 receptor activation produces opposing physiological outcomes in dopamine neurons depending on the receptor's location.	Foster DJ et al.	—	2014	→
Neonatal estradiol stimulation prevents epilepsy in Arx model of X-linked infantile spasms syndrome.	Olivetti PR et al.	—	2014	→
Procedural-based category learning in patients with Parkinson's disease: impact of category number and category continuity.	Filoteo JV et al.	—	2014	→
Striatal cholinergic cell ablation attenuates L-DOPA induced dyskinesia in Parkinsonian mice.	Won L et al.	—	2014	→
Different correlation patterns of cholinergic and GABAergic interneurons with striatal projection neurons.	Adler A et al.	—	2013	→
Effects of treadmill training on limb motor function and acetylcholinesterase activity in rats with stroke.	Kim G et al.	—	2013	→
Extrasynaptic muscarinic acetylcholine receptors on neuronal cell bodies regulate presynaptic function in Caenorhabditis elegans.	Chan JP et al.	—	2013	→
Genetic and neurophysiological correlates of the age of onset of alcohol use disorders in adolescents and young adults.	Chorlian DB et al.	—	2013	→
Glycogen synthase kinase-3 reduces acetylcholine level in striatum via disturbing cellular distribution of choline acetyltransferase in cholinergic interneurons in rats.	Zhao L et al.	—	2013	→
Translational research in nicotine dependence.	Turner JR et al.	—	2013	→
Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior.	Picciotto MR et al.	—	2012	→
Dopaminergic modulation of synaptic transmission in cortex and striatum.	Tritsch NX et al.	—	2012	→
Effects of acetylcholine in the striatum. Recent insights and therapeutic implications.	Benarroch EE	—	2012	→
Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks.	Fuxe K et al.	—	2012	→
Opposing regulation of dopaminergic activity and exploratory motor behavior by forebrain and brainstem cholinergic circuits.	Patel JC et al.	—	2012	→
Sex differences in the neural mechanisms mediating addiction: a new synthesis and hypothesis.	Becker JB et al.	—	2012	→
Striatal microcircuitry and movement disorders.	Gittis AH et al.	—	2012	→
Synergistic roles for G-protein γ3 and γ7 subtypes in seizure susceptibility as revealed in double knock-out mice.	Schwindinger WF et al.	—	2012	→