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Emergence of novel functions in striatal low-threshold spike interneurons (Commentary on Gazan et al., 2019)
1Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ, USA.
Abstract:
LTSIs selectively target distal dendrites of spiny projection neurons (SPNs, top). In this article by Gazan et al., the authors performed a selective ablation of LTSIs using Cre-dependent diphtheria toxin in SST-Cre mice, injected in the striatum. They demonstrate that the ablation of LTSIs (bottom) induced a decrease in the number of distal dendritic spines on SPNs associated with an increased intrinsic excitability of these cells. Behaviorally, this is associated with a potentiation of cocaine effect on locomotion. Whether these behavioral effects are the direct result of the loss of LTSIs or whether it involves rearrangements in glutamatergic (Glu) or dopaminergic (DA) synapses occurring normally on these dendritic spines remains to be explored. Commentary on Gazan A, Rial D, Schiffmann SN. Ablation of striatal somatostatin interneurons affects MSN morphology and electrophysiological properties, and increases cocaine induced hyperlocomotion in mice. Eur J Neurosci. 2020;51:1388-1402. https://doi.org/10.1111/ejn.14581.
Insights
Ablating somatostatin interneurons (LTSIs) in mice reduced dendritic spines on projection neurons, increasing their excitability and enhancing cocaine
Area of Science:
- Neuroscience
- Cell Biology
- Neuropharmacology
Background:
- Striatal spiny projection neurons (SPNs) are modulated by local interneurons.
- Somatostatin-expressing interneurons (LTSIs) are key inhibitory cells in the striatum.
- The precise role of LTSIs in modulating SPN dendritic morphology and function is not fully understood.
Purpose of the Study:
- To investigate the functional role of LTSIs in the striatum.
- To determine the impact of LTSIs on SPN dendritic spine morphology and intrinsic excitability.
- To assess the behavioral consequences of LTSIs ablation, particularly concerning psychostimulant effects.
Main Methods:
- Selective ablation of LTSIs in SST-Cre mice using Cre-dependent diphtheria toxin.
- Electrophysiological recordings to assess SPN intrinsic excitability.
- Dendritic spine density analysis on SPNs.
- Behavioral testing of locomotion in response to cocaine.
Main Results:
- LTSIs ablation led to a decrease in distal dendritic spines on SPNs.
- The intrinsic excitability of SPNs was significantly increased following LTSIs ablation.
- Cocaine-induced locomotion was potentiated in mice with ablated LTSIs.
Conclusions:
- LTSIs play a critical role in regulating SPN dendritic spine morphology and neuronal excitability.
- The loss of LTSIs alters striatal circuits, leading to enhanced responses to psychostimulants like cocaine.
- Further research is needed to elucidate the synaptic mechanisms underlying these observed effects.
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