Table 1.

Neurobiological mechanisms of forgetting.

	Sleep independent mechanisms
Neurogenesis-dependent overwriting	The incorporation of new born neurons into hippocampal circuitries re-organizes existing connections and over-writes information stored in previously formed wiring diagrams. Neurogenesis associated re-wiring may gradually decrease the size and fidelity of, as well as accessibility to, engrams
Pro-active interference	Older information represented in stabilized wiring diagrams can impede the recall or storage of new information
Retro-active interference	Old information can be over-written by new information recruiting similar circuitries, due to a reallocating of cellular materials (biochemical and circuit resources)
Engram instability	Information stored as metabolic change is inherently unstable as biochemical changes are subject to regular turnover and degradation
	Sleep dependent mechanisms
Sharp wave replay	Select information replayed in sharp-waves weakens as these oscillations produce presynaptic and postsynaptic decoupling and engage depotentiation pathways
Homeostatic synaptic downscaling	Sleep sees a proportional downscaling of synaptic weights aimed at preventing run-away potentiation and resource exhaustion. This downscaling operates through a biochemical mechanism involving Homerla. Though, electrophysiologically evoked mechanisms are also involved; see row 8
Theta trough replay	Information replayed during periods of decreased neuronal excitability (theta troughs) engages depotentiation or LTD-like pathways
Low frequency oscillation evoked depotentiation	Low frequency oscillations can decouple synaptic activity and evoke biochemical cascades that disintegrate engrams

Shown are brief descriptions of several sleep independent (rows 1–4) and sleep-dependent (rows 5–8) forgetting mechanisms.