Heart-Specific Spinal and Vagal Afferents: Transcriptomic Signatures and Optogenetically Modulated Functional...

Area of Science:

• Neuroscience
• Cardiology
• Molecular Biology

Background:

• Heart-innervating sensory neurons, including dorsal root ganglion (DRG) and nodose ganglion (NG) neurons, are crucial for cardiac pain and reflexes.
• The specific molecular and functional characteristics of these heart-specific sensory (HS) neurons remain largely unknown.

Purpose of the Study:

• To molecularly and functionally characterize DRG^HS and NG^HS neurons that innervate the heart.
• To elucidate the neuro-cardiac communication pathways and identify potential therapeutic targets.

Main Methods:

• Purification of DRG^HS and NG^HS neurons using fluorescence-activated cell sorting (FACS) with retrograde labeling.
• Molecular characterization via bulk RNA sequencing.
• Functional evaluation through co-cultures with neonatal cardiomyocytes and optogenetic manipulation.

Main Results:

• DRG^HS and NG^HS neurons established functional connections with cardiomyocytes, showing enhanced Ca²⁺ activity upon stimulation.
• Distinct transcriptomic profiles were observed between DRG^HS and NG^HS neurons and their total populations.
• Key genes like Scn10a, P2xr2, Mrgprd (DRG^HS) and P2xr2, Ptgdr, Cckar (NG^HS) were identified, suggesting nociceptor roles.

Conclusions:

• Defined distinct molecular profiles for heart-innervating sensory neurons from DRG and NG.
• Demonstrated functional neuro-cardiac communication, highlighting dynamic interactions.
• Identified specific molecular signatures that offer potential targets for modulating cardiovascular reflexes and hemostasis.