Homeostatic metaplasticity of corticospinal excitatory and intracortical inhibitory neural circuits in human motor cortex

• Published in: The Journal of physiology Vol. 590; no. 22; pp. 5765 - 5781
• Main Authors: Murakami, Takenobu, Müller‐Dahlhaus, Florian, Lu, Ming‐Kuei, Ziemann, Ulf
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 15.11.2012; Wiley Subscription Services, Inc; Blackwell Science Inc
• Subjects: Achievement tests; Adult; Evoked Potentials, Motor; Female; GABAergic Neurons - physiology; Homeostasis - physiology; Humans; Long-Term Potentiation; Long-Term Synaptic Depression; Male; Motor Cortex - physiology; Nerve Net - physiology; Neural Inhibition; Neuroscience: Behavioural/Systems/Cognitive; Physiology; Pyramidal Tracts - physiology; Theta Rhythm; Transcranial Magnetic Stimulation
• ISSN: 0022-3751; 1469-7793; 1469-7793
• DOI: 10.1113/jphysiol.2012.238519

Key points •  Homeostatic metaplasticity is an important mechanism for maintaining overall synaptic weight of a neuronal network in the physiological range. •  Homeostatic metaplasticity has been demonstrated, so far largely exclusively, for excitatory synaptic neurotransmission. •  New non‐invasive transcranial magnetic theta burst stimulation (TBS) experiments at the systems level of human motor cortex demonstrate for the first time that homeostatic metaplasticity is also present in inhibitory intracortical circuits. •  In addition, manipulation of intracortical inhibition by priming TBS contributes to the homeostatic regulation of metaplasticity in the corticospinal excitatory pathway. •  Findings are important for therapeutic applications of non‐invasive brain stimulation that aim at correcting excitatory or inhibitory neurotransmission outside the physiological range in humans with neuropsychiatric disorders.   Homeostatic metaplasticity, a fundamental principle for maintaining overall synaptic weight in the physiological range in neuronal networks, was demonstrated at the cellular and systems level predominantly for excitatory synaptic neurotransmission. Although inhibitory networks are crucial for regulating excitability, it is largely unknown to what extent homeostatic metaplasticity of inhibition also exists. Here, we employed intermittent and continuous transcranial magnetic theta burst stimulation (iTBS, cTBS) of the primary motor cortex in healthy subjects for induction of long‐term potentiation (LTP)‐like and long‐term depression (LTD)‐like plasticity. We studied metaplasticity by testing the interactions of priming TBS with LTP/LTD‐like plasticity induced by subsequent test TBS. Changes in excitatory neurotransmission were measured by the input–output curve of motor‐evoked potentials (IO‐MEP), and changes in GABAAergic inhibitory neurotransmission by the IO of short‐interval intracortical inhibition (IO‐SICI, four conditioning stimulus intensities of 70–100% active motor threshold, interstimulus interval 2.0 ms). Non‐primed iTBS increased IO‐MEP, while non‐primed cTBS decreased IO‐MEP. Pairing of identical protocols (iTBS→iTBS, cTBS→cTBS) resulted in suppression of the non‐primed TBS effects on IO‐MEP, and pairing of different protocols (cTBS→iTBS, iTBS→cTBS) enhanced the test TBS effects on IO‐MEP. While non‐primed TBS did not result in significant changes of IO‐SICI, iTBS→iTBS resulted in IO‐SICI decrease, and cTBS→cTBS in IO‐SICI increase compared with the non‐primed conditions. The changes in SICI induced by priming TBS correlated with the changes in MEP induced by subsequent test TBS. Findings demonstrate that plasticity in both excitatory and inhibitory circuits in the human motor cortex are regulated by homeostatic metaplasticity, and that priming effects on inhibition contribute to the homeostatic regulation of metaplasticity in excitatory circuits.