Aruna Surendran Ramkrishnan

Infraorbital nerve‐chronic constriction injury (ION‐CCI) has become the most popular chronic trigeminal neuropathic pain (TNP) injury animal model which causes prolonged mechanical allodynia. Accumulative evidence suggests that TNP interferes with cognitive functions, however the underlying mechanisms are not known. The aim of this study was to investigate decision‐making performance as well as synaptic and large‐scale neural synchronized alterations in the spinal trigeminal nucleus (SpV) circuitry and anterior cingulate cortex (ACC) neural circuitry in male rats with TNP. Rat gambling task showed that ION‐CCI led to decrease the proportion of good decision makers and increase the proportion of poor decision makers. Electrophysiological recordings showed long‐lasting synaptic potentiation of local field potential in the trigeminal ganglia‐SpV caudalis (SpVc) synapses in TNP rats. In this study, TNP led to disruption of ACC spike timing and basolateral amygdala (BLA) theta oscillation associated with suppressed synchronization of theta oscillation between the BLA and ACC, indicating reduced neuronal communications. Myelination is critical for information flow between brain regions, and myelin plasticity is an important feature for learning. Neural activity in the cortical regions impacts myelination by regulating oligodendrocyte (OL) proliferation, differentiation, and myelin formation. We characterized newly formed oligodendrocyte progenitor cells, and mature OLs are reduced in TNP and are associated with reduced myelin strength in the ACC region. The functional disturbances in the BLA‐ACC neural circuitry is pathologically associated with the myelin defects in the ACC region which may be relevant causes for the deficits in decision‐making in chronic TNP state.

Memory is a dynamic brain function that is continually processed after encoding. Although psychologic concepts of mental schema are now well established, they have rarely been considered in animal studies. We used a behavior paradigm of multiple flavor‐place paired associates (PAs) and showed that memory schema facilitates fast acquisition of new PAs in a single trial. The hippocampus is necessary for the encoding of new PAs and for memory retrieval within a certain time window—24 h following new PA consolidation. Whereas the anterior cingulate cortex (ACC) plays a critical role for dynamic PA learning and consolidation during training sessions, ACC is essential in schema representation and activation. New myelin generation is essential for learning. Neural activity in the cortical regions impacts myelination by regulating oligodendrocyte (OL) proliferation, differentiation, and myelin formation. Here, we show that newly formed OL progenitor cells and mature OLs are increased following repeated PA learning and that establishment of the memory schema is associated with enhanced myelin strength in the ACC region. Furthermore, to ensure that myelination is necessary for the acquisition of paired‐associate learning, ACC lysolecithin‐induced demyelination revealed impaired PA learning associated with decrease in ACC θ band power and reduced spike‐field coherence and phase‐locking in ACC.—Hasan, M., Kanna, M. S., Jun, W., Ramkrishnan, A. S., Iqbal, Z., Lee, Y., Li, Y. Schema‐like learning and memory consolidation acting through myelination. FASEB J. 33, 11758–11775 (2019). www.fasebj.org