Pairedpulse

Pairedpulse is a neurophysiological and neurostimulation experimental paradigm in which two stimuli are delivered to a neural pathway or circuit with a defined interstimulus interval (ISI). The response to the second stimulus is compared with the first to quantify short-term changes in synaptic strength or neural excitability. The framework is used across in vitro and in vivo preparations, including brain slices, animal models, and human studies.

In synaptic physiology, paired-pulse effects reflect short-term plasticity. At short ISIs, the second response often shows facilitation, known as paired-pulse facilitation (PPF), which is commonly attributed to residual calcium in the presynaptic terminal that increases the probability of neurotransmitter release. At longer ISIs, paired-pulse depression (PPD) may occur due to vesicle depletion, receptor desensitization, or inhibitory feedback within the circuit. The balance between facilitation and depression depends on synaptic type, release probability, and the postsynaptic machinery.

In human neuroscience and clinical research, paired-pulse protocols are applied in transcranial magnetic stimulation (ppTMS) and electrical stimulation to probe intracortical excitability and connectivity. For example, a subthreshold conditioning stimulus followed by a suprathreshold test stimulus at short intervals assesses short-interval intracortical inhibition, while longer intervals can reveal intracortical facilitation. Similar approaches are used in motor and sensory pathways to infer synaptic dynamics and cortical circuit function.

Data from paired-pulse experiments are typically expressed as the ratio or percent change of the second response relative to the first. While informative, interpretation requires careful control of stimulus intensity, timing, and physiological state, as results can be influenced by non-synaptic factors and experimental conditions.