Striatal Neuropeptides Enhance Selection and Rejection of Sequential Actions

Area of Science:

• Neuroscience
• Computational Neuroscience
• Systems Neuroscience

Background:

• The striatum, a key basal ganglia component, processes cortical inputs for action selection.
• Medium spiny neurons (MSNs) in the striatum form a network to filter action requests.
• The role of neuropeptides like Substance P (SP) and enkephalin in action sequencing remains unclear.

Purpose of the Study:

• To investigate the role of SP and enkephalin in action selection and sequencing within the striatum.
• To model how neuropeptide interactions influence the processing of action requests.
• To understand the mechanisms underlying rapid, clean switching between actions in learned sequences.

Main Methods:

• Developed phenomenological models for SP and enkephalin effects.
• Integrated these models into a hybrid computational model of the basal ganglia.
• Simulated a spiking striatal microcircuit alongside rate-coded populations for other basal ganglia structures.

Main Results:

• Diffuse neuropeptide connectivity facilitated the selection of unordered action requests.
• Patterned SP connectivity, reflecting action sequence structure, improved ordered action selection and suppressed incorrect sequences.
• Selective pruning of SP connections enabled context-sensitive inhibition of interfering action requests.

Conclusions:

• The interaction between SP and enkephalin enhances the contrast between action selection and rejection.
• Patterned SP connectivity in the striatum supports action 'chunking' and improves sequence selection.
• Efficient action sequence execution likely results from ordered cortical inputs and patterned neuropeptide connectivity.