Pulsed infrared light for modulating neuromuscular transmission

Infrared (IR) neuromodulation (INM) has emerged as a new modality that can reliably modulate both neural and muscular activities using pulsed IR light without the requirement of any chemical or genetic manipulation of the target tissue. However, despite the successful demonstration of INM in a wide range of biological systems, the overall function of a neuron that can be altered by pulsed IR light, including its intrinsic excitability, integration of synaptic inputs, and downstream synaptic outputs, has yet to be examined systematically. This dissertation aims to investigate the IR light-mediated modulation of axonal excitability, action potential (AP) initiation and propagation, and synaptic transmission with the crayfish opener neuromuscular preparation. A custom-built thulium-doped fiber amplification system is designed and constructed as the source for generating IR light pulses around a 2-µm wavelength. The studies presented in this dissertation cover the effects of IR light pulse parameters on the excitability of axonal membrane and the resulting functional outcomes in terms of AP initiation and firing, the INM of locally evoked and propagating APs under different physiological conditions and the corresponding postsynaptic responses, and the direct impacts of pulsed IR light on the evoked synaptic transmission. A single IR light pulse is shown to induce membrane depolarization and hyperpolarization sequentially on individual motor axons in a pulse parameter-dependent manner, which can facilitate and disrupt axonal AP firing, respectively. Moreover, pulsed IR light is discovered to modulate the axonal AP generation, propagation, waveform, and firing frequency depending on the physiological and anatomical contexts of the APs, which can lead to alterations in downstream postsynaptic responses accordingly. It is also demonstrated for the first time that pulsed IR light specifically targeting synapses can serve as a reliable and flexible modality to bidirectionally control the evoked synaptic transmission. The underlying mechanisms of these observations are explored. In summary, the results in this dissertation highlight the necessity of the collective evaluation of both the excitatory and the inhibitory effects that can be induced by pulsed IR light in INM. The dissertation establishes a mechanistic framework for understanding how a neuron and its function as a whole can be modulated by pulsed IR light and thus provides valuable insights into the INM of complex neuronal networks and the development of translational applications.2023-08-31T00:00:00