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Interpericyte tunnelling nanotubes regulate neurovascular coupling.

Luis Alarcon-Martinez1,2, Deborah Villafranca-Baughman3,4, Heberto Quintero3,4

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Newly discovered interpericyte tunnelling nanotubes (IP-TNTs) connect retinal pericytes, enabling communication and coordinating blood flow with neuronal activity. Damage to these nanotubes impairs neurovascular coupling, while their preservation restores function.

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Physiology

Background:

  • Neurovascular coupling matches blood flow to neuronal activity.
  • Pericytes are strategically located on capillaries and regulate microcirculation.
  • The role of pericytes in coordinating capillary networks was previously unknown.

Purpose of the Study:

  • To investigate the existence and function of connections between pericytes.
  • To determine if pericytes synchronize microvascular dynamics and neurovascular coupling.
  • To elucidate the role of these connections in the mouse retina.

Main Methods:

  • Identification of interpericyte tunnelling nanotubes (IP-TNTs) using two-photon microscopy in mouse retina.
  • Analysis of IP-TNT structure, organelle transport, and calcium (Ca2+) wave propagation.
  • Assessment of IP-TNT function in response to light stimulation, ablation, ischemia, and pharmacological intervention.

Main Results:

  • Discovered IP-TNTs connecting separate pericytes, forming a functional network.
  • Demonstrated IP-TNTs facilitate intercellular Ca2+ waves and organelle transport.
  • Showed IP-TNTs are crucial for coordinating light-evoked responses and regulating neurovascular coupling.
  • Found that IP-TNT damage impairs blood flow regulation, while preservation rescues function.

Conclusions:

  • IP-TNTs are a novel structural and functional component of the retinal neurovascular unit.
  • These nanotubes mediate communication between pericytes, essential for coordinated capillary network function.
  • IP-TNTs play a critical role in regulating neurovascular coupling under physiological and pathological conditions.