The less things change, the more they are different: contributions of long-term synaptic plasticity and homeostasis to memory

Abstract

An important cellular mechanism contributing to the strength and duration of memories is activity-dependent alterations in the strength of synaptic connections within the neural circuit encoding the memory. Reversal of the memory is typically correlated with a reversal of the cellular changes to levels expressed prior to the stimulation. Thus, for stimulus-induced changes in synapse strength and their reversals to be functionally relevant, cellular mechanisms must regulate and maintain synapse strength both prior to and after the stimuli inducing learning and memory. The strengths of synapses within a neural circuit at any given moment are determined by cellular and molecular processes initiated during development and those subsequently regulated by the history of direct activation of the neural circuit and system-wide stimuli such as stress or motivational state. The cumulative actions of stimuli and other factors on an already modified neural circuit are attenuated by homeostatic mechanisms that prevent changes in overall synaptic inputs and excitability above or below specific set points (synaptic scaling). The mechanisms mediating synaptic scaling prevent potential excitotoxic alterations in the circuit but also may attenuate additional cellular changes required for learning and memory, thereby apparently limiting information storage. What cellular and molecular processes control synaptic strengths before and after experience/activity and its reversals? In this review we will explore the synapse-, whole cell-, and circuit level-specific processes that contribute to an overall zero sum-like set of changes and long-term maintenance of synapse strengths as a consequence of the accommodative interactions between long-term synaptic plasticity and homeostasis.Long-term changes in the strength of synapses-long-term potentiation/facilitation (LTP or LTF) and long-term depression (LTD)-are critical cellular mechanisms in modulating the amplitude and duration of behavioral modifications or the storage of memories (Kandel 2001). These synaptic changes could lead to significant and long-lasting bidirectional changes in the excitability of some neurons within a neural circuit, which under extreme circumstances can lead to excitotoxic or degenerative consequences that impact on cell function or survival, or the storage of memory (Abbott and Nelson 2000;Nelson and Turrigiano 2008). To prevent these maladaptive processes, homeostatic mechanisms restrain the overall weights of synaptic inputs and excitation/ inhibition balance to ensure that neurons remain functional (including the ability to express additional activity-dependent plasticity) while the storage of information acquired by previous activity is maintained (Davis 2006;Marder and Goaillard 2006;Roth-Alpermann et al. 2006;Ibata et al. 2008;Kim and Tsien 2008;Turrigiano 2008).The mechanisms mediating synaptic scaling/homeostasis at the level of individual neurons include those that regulate presynaptic transmitter release by affecting structure/function properties of...

Structural Components of Synaptic Plasticity and Memory Consolidation

“…The association between alterations in the structure and/or number of synapses and memory storage has led to numerous studies regarding the signaling pathways that might couple molecular changes to structural changes. In addition, parallel homeostatic mechanisms have been identified that can trigger synaptic scaling, which serves to stabilize the strengthened synapses while weakening or eliminating other synapses, thus providing specificity during memory consolidation (Bourne and Harris 2011;Schacher and Hu 2014).…”

Control of lung ventilation following overwintering conditions in bullfrogs,Lithobates catesbeianus

“…From the neural perspective, a wealth of information exists regarding how neurons and circuits maintain target levels of activity despite removing or enhancing activity inputs (termed homeostatic plasticity). However, models to study these processes use pharmacological or pathological paradigms to manipulate neuronal activity in vivo and in vitro primarily at early developmental stages (Hengen et al, 2013;Knogler et al, 2010;Ngodup et al, 2015;Schacher and Hu, 2014;Turrigiano, 2012;Wilhelm and Wenner, 2008). Thus, the bullfrog respiratory control system following overwintering offers a powerful ability to uncover mechanisms leading to and resulting in the preservation (respiratory motor output and hypoxia sensitivity) and deterioration (CO 2 sensitivity) of sensorimotor function in the same species, individual and neural control system after ecologically relevant inactivity.…”

DNA methylation and the regulation of stimulus-specific memory formation

“…Hebbian plasticity at individual synapses) in order to normalise overall activity levels and prevent extrema (for review see: GuzmanKarlsson et al (2014); Schacher and Hu (2014); Yin and Yuan (2015)). Homoeostatic mechanisms are induced by and utilize mechanisms (e.g.…”

“…primary excitatory pathway in vertebrate brain) (Schacher and Hu, 2014). Insects, however, use acetylcholine as their primary excitatory neurotransmitter (Breer and Sattelle, 1987).…”

“…Homeostatic plasticity comprises of mechanisms which adjust the excitability, activity and overall synaptic weight of individual neurons and the overall neuronal network (Schacher and Hu, 2014;Yin and Yuan, 2015). Several aspects of the data presented in this thesis argue towards DNA methylation -specifically de novo methylation -potentially affecting homeostatic, rather than Hebbian, plasticity in honey bees: (1) Dnmt3 was upregulated 5 hours after olfactory reward conditioning (Chapter 4), suggesting Dnmt3 is likely required during a period in which homeostatic, rather than Hebbian plasticity, plays a role (Fig.…”