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Functional connectome of the striatal medium spiny neuron
Nao Chuhma1, Kenji F Tanaka, René Hen
1Department of Psychiatry and Pharmacology, Columbia University, New York, NY 10032, USA.
Summary
Researchers mapped the connections of medium spiny neurons (MSNs), crucial for dopamine disorders. Optogenetics revealed their specific functional connectivity within the striatum and to downstream brain regions.
Area of Science:
- Neuroscience
- Neurobiology
- Systems Neuroscience
Background:
- Medium spiny neurons (MSNs) are central to dopamine system disorders, including movement disorders, addiction, and schizophrenia.
- Understanding the functional connectivity of MSNs is critical but has been challenging.
- The precise network of MSN connections within the striatum and their projections to the globus pallidus and substantia nigra remains incompletely defined.
Purpose of the Study:
- To comprehensively determine the functional connectivity of striatal medium spiny neurons (MSNs).
- To assess the specificity and strength of MSN intrinsic connections within the striatum.
- To map MSN projections and their functional interactions with the globus pallidus and substantia nigra.
Main Methods:
- Generation of a mouse model with conditional channelrhodopsin-2 expression specifically in MSNs.
- Optogenetic stimulation of MSNs to assess their connections in the striatum, globus pallidus, and substantia nigra.
- Electrophysiological identification of postsynaptic neuronal populations and assessment of presynaptic modulation (inhibition/facilitation).
Main Results:
- In the striatum, MSNs connect with other MSNs and tonically active cholinergic interneurons, but not fast-spiking GABA interneurons.
- MSNs project strongly to one class of neurons in the globus pallidus and weakly to another.
- MSN projections to the substantia nigra connect strongly with GABA neurons but not dopamine neurons, exhibiting D2-mediated inhibition to the globus pallidus and D1-mediated facilitation to the substantia nigra.
Conclusions:
- This study defines the functional connectome of striatal medium spiny neurons using a novel optogenetic approach.
- The findings elucidate specific MSN communication pathways within the basal ganglia, crucial for understanding dopamine-related disorders.
- The results highlight distinct modulatory roles (D1/D2 mediated) of MSN projections to target brain regions.
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