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Updated: Jun 24, 2026
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Single Synapse Indicators of Glutamate Release and Uptake in Acute Brain Slices from Normal and Huntington Mice
Published on: March 11, 2020
Substance P mediates excitatory interactions between striatal projection neurons
Craig P Blomeley1, Laura A Kehoe, Enrico Bracci
1Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
Summary
Medium spiny neurons (MSNs) in the striatum release substance P (SP), which excites neighboring MSNs by acting on NK1 receptors. This finding updates the understanding of striatal networks beyond purely inhibitory interactions.
Area of Science:
- Neuroscience
- Cellular Neuroscience
- Synaptic Plasticity
Background:
- The striatum, a key basal ganglia component, is vital for motor control.
- Medium spiny neurons (MSNs) are the primary projection neurons in the striatum.
- The role of substance P (SP) released by a subset of MSNs in MSN-MSN communication remains largely unknown.
Purpose of the Study:
- To investigate the functional role of SP released by MSNs in modulating communication between neighboring MSNs.
- To determine if SP release influences glutamatergic responses in postsynaptic MSNs.
Main Methods:
- Whole-cell paired recordings from rat striatal MSNs in brain slices.
- Application of receptor antagonists (GABA, acetylcholine, dopamine, opioid) to isolate specific synaptic effects.
- Stimulation of MSN axon collaterals and antidromic stimulation of axons in the globus pallidus.
- Use of NK1 receptor antagonist L-732,138 to block SP-mediated effects.
Main Results:
- A subpopulation of MSNs (23%) exhibited spike-induced facilitation of glutamatergic responses in neighboring MSNs.
- This facilitation was maximal at 100 ms intervals and completely blocked by L-732,138, indicating NK1 receptor involvement.
- Antidromic stimulation of MSN axons potentiated subsequent glutamatergic responses, also blocked by L-732,138.
- These SP-mediated effects facilitated spike generation in postsynaptic MSNs.
Conclusions:
- MSNs can facilitate glutamatergic inputs to neighboring MSNs via spike-released SP acting on NK1 receptors.
- This demonstrates an excitatory interaction between MSNs, challenging the traditional view of solely inhibitory striatal networks.
- The findings necessitate an updated model of striatal circuitry that includes excitatory MSN-MSN communication.
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