Short-term synaptic plasticity, a temporary change in synaptic strength lasting from seconds to minutes, is a crucial mechanism for neural communication and information processing. Two key types of short-term plasticity are paired pulse facilitation (PPF) and paired pulse depression (PPD). Understanding these mechanisms can provide insight into the molecular & genetic underpinnings of autism.
Paired Pulse Facilitation (PPF) occurs when two signals (pulses) arrive in quick succession at a synapse, with the second pulse producing a stronger response than the first. This is due to residual calcium (Ca2+) remaining in the presynaptic terminal after the first pulse, which enhances neurotransmitter release upon the arrival of the second pulse. This phenomenon is particularly significant at synapses with low initial release probability, ensuring that enough neurotransmitters are available for subsequent release.
Paired Pulse Depression (PPD), on the other hand, is characterized by a diminished response to the second pulse. This occurs at synapses with high initial release probability, where the first pulse depletes the readily releasable pool of neurotransmitters, leaving insufficient resources for the second pulse. The timing between the pulses is critical; if the interval is too long, Ca2+ dissipates, and vesicles are replenished, mitigating these effects.
In the context of autism, alterations in short-term plasticity have been linked to the disorder’s characteristic neural and behavioral features. Research has shown that mutations in synaptic genes such as SYN1 and SYN2, which regulate synaptic vesicle dynamics, can disrupt short-term plasticity. These mutations result in increased PPF at excitatory synapses and enhanced synaptic depression at inhibitory synapses, leading to an excitatory/inhibitory (E/I) imbalance that contributes to network hyperexcitability and altered neuronal communication (Frontiers, 2015)​ (Frontiers)​.
Furthermore, neuroligin-3 mutations, associated with autism, have been found to differentially alter synaptic function in the hippocampus and cortex. These mutations can increase inhibitory synaptic transmission and disrupt endocannabinoid signaling, further impacting short-term plasticity and neural circuitry (Molecular Psychiatry, 2015)​ (Nature)​. These findings underscore the significant role of short-term plasticity in maintaining neural circuit function and how its disruption can contribute to pathogenesis.
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