Mechanisms of Hebbian‐like plasticity in the ventral premotor – primary motor network. (29th November 2022)

• Record Type: Journal Article
• Authors: Casarotto, Andrea; Dolfini, Elisa; Cardellicchio, Pasquale; Fadiga, Luciano; D'Ausilio, Alessandro; Koch, Giacomo
• Is Part Of: Journal of physiology. Volume 601:Number 1(2023)
• Page Start: 211
• Page End: 226
• Publication Date: 2022-11-29
• Subjects: cortico‐cortical paired associative stimulation -- Hebbian‐like plasticity -- I‐waves -- LTP‐like and LTD‐like after‐effect -- primary motor cortex -- ventral premotor cortex; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP283560
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Abstract: The functional connection between ventral premotor cortex (PMv) and primary motor cortex (M1) is critical for the organization of goal‐directed actions. Repeated activation of this connection by means of cortico‐cortical paired associative stimulation (cc‐PAS), a transcranial magnetic stimulation (TMS) protocol, may induce Hebbian‐like plasticity. However, the physiological modifications produced by Hebbian‐like plasticity in the PMv‐M1 network are poorly understood. To fill this gap, we investigated the effects of cc‐PAS on PMv‐M1 circuits. We hypothesized that specific interactions would occur with I2 ‐wave interneurons as measured by the short intracortical facilitation protocol (SICF). We used different paired‐pulse TMS protocols to examine the effects of PMv‐M1 cc‐PAS on SICF, on GABAergic circuits as measured by short (SICI) and long (LICI) intracortical inhibition protocols, and varied the current direction in M1 to target different M1 neuronal populations. Finally, we examined the effects of cc‐PAS on PMv‐M1 connectivity using a dual coil approach. We found that PMv‐M1 cc‐PAS induces both a long‐term potentiation (LTP)‐ or long‐term depression (LTD)‐like after‐effect in M1 neuronal activity that is strongly associated with a bidirectional‐specific change in I2 ‐wave activity (SICF = 2.5 ms ISI). Moreover, cc‐PAS induces a specific modulation of the LICI circuit and separately modulates PMv‐M1 connectivity. We suggest that plasticity within the PMv‐M1 circuit is mediated by a selective mechanism exerted by PMv on M1 by targeting I2 ‐wave interneurons. These results provide new mechanistic insights into how PMv modulates M1 activity that are relevant for the design of brain stimulation protocols in health and disease. Key points: The I2 ‐wave is specifically modulated by the induction of ventral premotor cortex – primary motor cortex (PMv‐M1) plasticity. After PMv‐M1 cortico‐cortical paired associative stimulation (cc‐PAS), corticospinal excitability correlates negatively with I2 ‐wave amplitude. Different cc‐PAS coil orientations can lead to a long‐term potentiation‐ or long‐term depression‐like after‐effect in M1. Abstract : Abstract figure legend The neural circuits involved in plasticity induction after the ventral premotor cortex to primary motor cortex (PMv‐to‐M1) cortico‐cortical paired associative stimulation (cc‐PAS). Left, the cc‐PAS coil orientations: postero‐anterior (PA) and antero‐posterior (AP). Right blocks show the neural circuits preferentially activated by the different coil orientations. The pyramidal neuron (PN) (purple) receives both excitatory (red) and inhibitory (grey) synaptic inputs responsible for the generation of I2 ‐waves. The PMv projections (light blue) contact the interneurons within M1 in both layers 2–3 (L2–3) and in L5. The cc‐PASPA protocol preferentially target the deep neuron populations in L5, increasing the corticospinal excitability (CSE) and inhibiting the I2 ‐wave circuits (top block). On the other side, AP stimulation activates the more superficial neuronal populations in L2–3, inhibiting the dendritic arbour of the PN, leading to a reduction of CSE and a simultaneous increase in the activity of the I2 ‐wave circuit (bottom block).