Oligodendrocyte lineage cells driven by neuronal activity in selected brain regions are required for episodic memory formation

Abstract

The formation of long-term episodic memories requires the activation of molecular mechanisms in several regions of the medial temporal lobe, including the hippocampus and anterior cingulate cortex (ACC). The extent to which these regions engage distinct mechanisms and cell types to support memory formation is not well understood. Recent studies reported that oligodendrogenesis is essential for learning and long-term memory; however, whether these mechanisms are required only in selected brain regions is still unclear. Also still unknown are the temporal kinetics of engagement of learning-induced oligodendrogenesis and whether this oligodendrogenesis occurs in response to neuronal activity. Here we show that in rats and mice, episodic learning rapidly increases the oligodendrogenesis and myelin biogenesis transcripts olig2, myrf, mbp, and plp1, as well as oligodendrogenesis, in the ACC but not in the dorsal hippocampus (dHC). Region-specific knockdown and knockout of Myrf, a master regulator of oligodendrocyte maturation, revealed that oligodendrogenesis is required for memory formation in the ACC but not the dHC. Chemogenetic neuronal silencing in the ACC showed that neuronal activity is critical for learning-induced oligodendrogenesis. Hence, an activity-dependent increase in oligodendrogenesis in selected brain regions, specifically in the ACC but not dHC, is critical for the formation of episodic memories.

A perspective on astrocyte regulation of neural circuit function and animal behavior

“…Similarly, oligodendrocytes can regulate neurons' axonal properties (e.g., conduction velocity) in an activity-and behavior-dependent manner. Astrocytes bidirectionally communicate with and regulate both microglia and oligodendrocytes (e.g., through diffusible messengers and physical interactions), allowing them to influence neural circuits indirectly and in a spatially and temporally distinct manner than their direct routes is also critical for spike-timing-dependent plasticity in neural circuits (Monje, 2018;Suminaite et al, 2019), and activity-dependent, brain region-specific oligodendrogenesis may be essential for episodic memory formation (Barboza et al, 2021).…”

“…Conversely, nutritional signals regulate OL proliferation, myelin regulatory factor-dependent perineuronal net remodeling, and tuning of the circuit that controls food intake and weight gain in the mediobasal hypothalamus ( Kohnke et al, 2021 ). Adaptive myelination is also critical for spike-timing-dependent plasticity in neural circuits ( Monje, 2018 ; Suminaite et al, 2019 ), and activity-dependent, brain region-specific oligodendrogenesis may be essential for episodic memory formation ( Barboza et al, 2021 ).…”