Cholinergic modulation of synaptic integration and dendritic excitability in the striatum.
- Authors
- Oldenburg, Ian AntΓ³n; Ding, Jun B
- Year
- 2011
- Journal
- Current opinion in neurobiology
- PMID
- 21550798
- DOI
- 10.1016/j.conb.2011.04.004
- PMCID
- PMC3138897
Modulatory interneurons such as, the cholinergic interneuron, are always a perplexing subject to study. Far from clear-cut distinctions such as excitatory or inhibitory, modulating interneurons can have many, often contradictory effects. The striatum is one of the most densely expressing brain areas for cholinergic markers, and actylcholine (ACh) plays an important role in regulating synaptic transmission and cellular excitability. Every cell type in the striatum has receptors for ACh. Yet even for a given cell type, ACh affecting different receptors can have seemingly opposing roles. This review highlights relevant effects of ACh on medium spiny neurons (MSNs) of the striatum and suggests how its many effects may work in concert to modulate MSN firing properties.
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.
Interactions between M1 and CB1 signallingIn the striatal medium spiny neuron, M1 receptor activation promotes PLCΞ²1/DAGLΞ±- 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).
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.
| 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 |
| GΞ²Ξ³ 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 |
| PLCΞ² 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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