Abstract:
Neocortical memory engrams are thought to mature via strengthened interconnectivity, yet synaptic plasticity alone cannot explain the dynamic vividness of enduring memories. Neuronal intrinsic excitability (IE) plasticity has been touted as an early priming mechanism that renders engram neurons susceptible to ongoing plastic processes and later encoding events. Here, we reveal that learning-induced IE plasticity of nascent anterior cingulate cortex (ACC) engram neurons is a permissive mechanism for the formation and specificity of remote memories. Using c-fos-dependent genetic/viral targeting in mice, we found that contextual fear learning triggered a time-limited increase in ACC engram IE during the early phase of memory formation. Remarkably, chemogenetically hyperpolarizing these neurons within-but not outside-the IE plasticity window strengthened consolidated memories, enhanced their context-precision, and prevented interference-induced engram reallocation. Thus, IE plasticity in nascent ACC engram neurons acts as an essential tagging mechanism that determines the fate and dynamic content of remote memories.

Abstract:
Breathing is a rhythmic behavior that requires organized contractions of respiratory effector muscles. This behavior must adapt to constantly changing conditions in order to ensure homeostasis, proper body oxygenation, and CO2/pH regulation. Respiratory rhythmogenesis is controlled by neural networks located in the brainstem. One area considered to be essential for generating the inspiratory phase of the respiratory rhythm is the preBotzinger complex (preBotC). Rhythmogenesis emerges from this network through the interplay between the activation of intrinsic cellular properties (pacemaker properties) and intercellular synaptic connections. Respiratory activity continuously changes under the impact of numerous modulatory substances depending on organismal needs and environmental conditions. The preBotC network has been shown to become active during the last third of gestation. But only little is known regarding the modulation of inspiratory rhythmicity at embryonic stages and even less on a possible role of pacemaker neurons in this functional flexibility during the prenatal period. By combining electrophysiology and calcium imaging performed on embryonic brainstem slice preparations, we provide evidence showing that embryonic inspiratory pacemaker neurons are already intrinsically sensitive to neuromodulation and external conditions (i.e., temperature) affecting respiratory network activity, suggesting a potential role of pacemaker neurons in mediating rhythm adaptation to modulatory stimuli in the embryo.