Competing for MemoryHippocampal LTP under Regimes of Reduced Protein Synthesis

Abstract

The persistence of synaptic potentiation in the hippocampus is known to depend on transcription and protein synthesis. We report here that, under regimes of reduced protein synthesis, competition between synapses for the relevant intracellular proteins can be demonstrated. Under such circumstances, the induction of additional protein synthesis-dependent long-term potentiation for a given set of postsynaptic neurons occurs at the expense of the maintenance of prior potentiation on an independent pathway. This new phenomenon, which we call "competitive maintenance," has important functional consequences, and it may be explained in terms of dynamic interactions between synapses and "plasticity factors" over extended periods of time.

Asymmetrical Synaptic Cooperation between Cortical and Thalamic Inputs to the Amygdale

“…As mentioned previously, the synaptic tagging and capture hypothesis proposes a cellular mechanism that enables the association of events separated in time (Fonseca et al, 2004;Frey and Morris, 1998a;Redondo et al, 2010). To test whether cortical and thalamic inputs cooperate, we stimulated the cortical inputs with a weak stimulation protocol and assessed whether subsequent strong stimulation of the thalamic input is sufficient to convert the transient cortical LTP (E-LTP) into a long-lasting LTP (L-LTP).…”

“…LTP maintenance is achieved by an interaction between input-specific 'synaptic tags', set by LTP induction, and the capture of PRPs synthesized in the soma or local dendritic domains. These are independent processes and can occur separately in time (Fonseca et al, 2004;Govindarajan et al, 2011;Redondo et al, 2010). Thus, according to the synaptic tagging and capture hypothesis, the maintenance of synaptic plasticity is a function of neuronal network activity and not only of the input stimulated at a given time.…”

Synapse-specific stabilization of plasticity processes: The synaptic tagging and capture hypothesis revisited 10 years later

“…In fact, under certain circumstances it can be a competitive process. Thus, under regimes of reduced protein synthesis, the induction of L-LTP in a given input occurs at the expense of the maintenance of prior potentation in an independent input (Fonseca et al, 2004) (Figure 2K). These findings extend the synaptic capture model in two important ways: (1) Newly produced plasticity related proteins (PRPs) are shared among synapses whose activity may have not contribute to their induction, such as observed in two-pathway synaptic capture experiments.…”

“…The STC hypothesis revisited 30 differential distribution of gene products from the soma to basal and apical dendrites (Alarcon et al, 2006;Fonseca et al, 2004;Sajikumar et al, 2007a;Sajikumar et al, 2007b). In consequence, gene products induced by signals that reach the nucleus seem to be primarily distributed back into the same dendritic compartment where the activation cascade was initiated.…”

An intriguing association between dental and mental pathology in addicted and control subjects: a cross-sectional survey

“…66 A serious hypothesis has developed that dental disorders may be associated with other systemic illnesses characterised by increased infl ammation, such as carotid atherosclerosis, 1,6 and this enjoyed currency particularly at the National Institute of Dental and Craniofacial Research (NIDCR), 58,67,68 although contrary evidence has also been described. 57 Similarly, it is now well known that there is intense interest in the role of stem cells in the adult brain, particularly with reference to function in memory [69][70][71] and emotional stability, [72][73][74][75] two areas which are particularly vulnerable in drug addiction. [76][77][78] A focus on cellular health, growth renewal and replication as is suggested in general terms by this report explains several seeming paradoxes in addiction medicine, such as a fi nding that on a genome-wide screen for genes up-regulated in addiction, genes corresponding to synapse formation, intracellular signalling and transcription factors were found to be most signifi cantly altered 79 and have been specifi cally identifi ed in studies of brain ageing.…”