Whole-brain mapping of long-range inputs to the VIP-expressing inhibitory neurons in the primary motor cortex

• Published in: Frontiers in neural circuits 2023-05, Vol.17, p.1093066-1093066
• Main Authors: Lee, Candice, Côté, Sandrine L, Raman, Nima, Chaudhary, Hritvic, Mercado, Bryan C, Chen, Simon X
• Format: Article
• Language: English
• Subjects: associative learning; Brain; Brain Mapping; Cortex (frontal); Cortex (motor); Experiments; Information processing; inhibitory neurons; Interneurons; Interneurons - physiology; monosynaptic circuit tracing; motor cortex; Motor Cortex - metabolism; Motor skill; Motor skill learning; Neural Circuits; Neurons; Neurons - physiology; Neuroplasticity; orbital frontal cortex (ORB); Parvalbumin; Parvalbumins - metabolism; Pyramidal cells; Rabies; Reinforcement; Somatosensory cortex; Somatostatin; Thalamic nuclei; Thalamus; Vasoactive agents; Vasoactive intestinal peptide; Vasoactive Intestinal Peptide - metabolism; γ-Aminobutyric acid
• ISSN: 1662-5110; 1662-5110
• DOI: 10.3389/fncir.2023.1093066

The primary motor cortex (MOp) is an important site for motor skill learning. Interestingly, neurons in MOp possess reward-related activity, presumably to facilitate reward-based motor learning. While pyramidal neurons (PNs) and different subtypes of GABAergic inhibitory interneurons (INs) in MOp all undergo cell-type specific plastic changes during motor learning, the vasoactive intestinal peptide-expressing inhibitory interneurons (VIP-INs) in MOp have been shown to preferentially respond to reward and play a critical role in the early phases of motor learning by triggering local circuit plasticity. To understand how VIP-INs might integrate various streams of information, such as sensory, pre-motor, and reward-related inputs, to regulate local plasticity in MOp, we performed monosynaptic rabies tracing experiments and employed an automated cell counting pipeline to generate a comprehensive map of brain-wide inputs to VIP-INs in MOp. We then compared this input profile to the brain-wide inputs to somatostatin-expressing inhibitory interneurons (SST-INs) and parvalbumin-expressing inhibitory interneurons (PV-INs) in MOp. We found that while all cell types received major inputs from sensory, motor, and prefrontal cortical regions, as well as from various thalamic nuclei, VIP-INs received more inputs from the orbital frontal cortex (ORB) - a region associated with reinforcement learning and value predictions. Our findings provide insight on how the brain leverages microcircuit motifs by both integrating and partitioning different streams of long-range input to modulate local circuit activity and plasticity.