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Anatomical mapping of whole-brain monosynaptic inputs to the orbitofrontal cortex
Mei Yang1,2, Hailing Yang1,2, Lang Shen1,2
1Laboratory Animal Center, Fudan University, Shanghai, China.
Frontiers in Neural Circuits
|April 21, 2025
Summary
Researchers mapped brain connections to the orbitofrontal cortex (ORB) subregions in mice. Distinct inputs to the medial, ventrolateral, and lateral ORB reveal new insights into brain circuitry and psychiatric disorders.
Area of Science:
- Neuroscience
- Neuroanatomy
- Systems Neuroscience
Background:
- The orbitofrontal cortex (ORB) is crucial for emotion regulation, decision-making, and reward processing.
- Its three subregions—medial (ORBm), ventrolateral (ORBvl), and lateral (ORBl)—have distinct functions, but their underlying neurocircuitry is poorly understood.
- ORB dysregulation is linked to psychiatric disorders.
Purpose of the Study:
- To elucidate the monosynaptic input patterns to the three subregions of the orbitofrontal cortex (ORBm, ORBvl, ORBl) in mice.
- To provide a comprehensive map of the functional connectivity within the ORB.
- To offer insights into the neural circuit mechanisms underlying ORB function and dysfunction.
Main Methods:
- Utilized recombinant adeno-associated viruses (rAAV) and glycoprotein-deleted rabies virus (RV-ΔG) for retrograde tracing.
- Investigated monosynaptic inputs to ORBm, ORBvl, and ORBl in male C57BL/6J mice.
- Quantified inputs across the whole brain using fluorescence imaging and statistical analysis.
Main Results:
- Identified distinct input patterns specific to each ORB subregion.
- ORBm received significant inputs from the prelimbic cortex, agranular insular cortex, and hippocampal CA1.
- ORBvl showed substantial intra-ORB connectivity, while ORBl received strong inputs from somatomotor and somatosensory cortices.
- Thalamic nuclei, including the mediodorsal and submedial nuclei, provided widespread inputs to all ORB subregions.
Conclusions:
- The study provides a detailed map of the functional connectivity of orbitofrontal cortex subregions.
- Distinct input profiles suggest specialized roles for ORBm, ORBvl, and ORBl in neural circuits.
- These findings advance our understanding of brain circuitry relevant to behavior and psychiatric disorders.
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