Reinforcement of rat hippocampal LTP by holeboard training

Abstract

Hippocampal long-term potentiation (LTP) can be dissociated in early-LTP lasting 4-5 h and late-LTP with a duration of more than 8 h, the latter of which requires protein synthesis and heterosynaptic activity during its induction. Previous studies in vivo have shown that early-LTP in the dentate gyrus can protein synthesis-dependently be transformed (reinforced) into late-LTP by the association of arousing novel environmental stimuli. Here we show that consolidation of spatial memory also reinforces early-LTP in the dentate gyrus. Both memory consolidation and LTP-reinforcement depend on protein synthesis. Four groups of animals were trained by five, seven, eight or 10 trials, respectively, to recognize a fixed pattern of baited holes. The last trial was performed 15 min after tetanus. Errors of long-term reference memory during the last trial were significantly decreased only in the eight-and 10-trial experimental groups compared to pseudo-trained animals. In correlation to this learning effect we found a reinforcement of early-LTP only in these experimental groups compared to controls. The data suggest that the synthesis of new proteins required for spatial reference-memory formation also contributes to LTP maintenance in the hippocampal dentate gyrus.Long-term potentiation (LTP), a widely studied cellular model for learning and memory formation, can-similar to memory forma tion (Flexner et al. 1965;Grecksch and Matthies 1980;Izquierdo et al. 2002)-be dissociated into an early phase and a late phase. We use the terms "early-LTP" for an initial phase of LTP with a 4-5-h duration that is protein synthesis-independent, and "late-LTP" for a late phase that protein synthesis-dependently maintains over more than 8 h. As pointed out by Kelleher III et al. (2004), these temporal phases of LTP were initially described by Krug et al. (1984) and Frey et al. (1988) and were confirmed by others in vivo (Otani and Abraham 1989;Otani and Ben-Ari 1993) and in vitro (Huang et al. 1994). It was shown that this kind of early-LTP is reinforceable in vivo; that is, it can protein synthesisdependently be transformed into late-LTP (Matthies et al. 1986), by a temporal-related second heterosynaptic input (Seidenbecher et al. 1997;Frey et al. 2001;Straube et al. 2003b). The induction of this form of LTP, in contrast to a short-term potentiation (Frey and Morris 1997), sets a tag at the potentiated synapses that then can profit from plasticity-related proteins, the synthesis of which was induced by the modulatory heterosynaptic inputs. Thus, the processing of the newly synthesized plasticity-related proteins by the tagged synapses allows the transformation of early-LTP into late-LTP. This is essential for reinforcement processes. There is a large body of literature reporting that the maintenance of memories also requires heterosynaptic activation (for review, see Bailey et al. 2000). Late-LTP is considered to be related to long-term memory, whereas early-LTP may represent short-term memory traces (Bach et al. 1999;Jones et al. 2001). T...

Induction of Long-Term Memory by Exposure to Novelty Requires Protein Synthesis: Evidence for a Behavioral Tagging

“…Third, the induction of inhibitory avoidance-LTM formation by spatial novelty was blocked by delivering the protein synthesis inhibitor anisomycin into the CA1 region immediately after the exposure to a novel environment. Frey and colleagues (Straube et al, 2003b;Uzakov et al, 2005) have previously found that novelty-and holeboard training-induced LTP reinforcement in the hippocampus, is dependent on new protein synthesis. Indeed, we demonstrated that the amnesia induced by blockade of protein synthesis immediately before strong inhibitory avoidance training was rescued by a previous exposure to novelty.…”

The Adult Visual Cortex Expresses Dynamic Synaptic Plasticity That Is Driven by the Light/Dark Cycle

“…4 D) (Bonferroni's test; p Ͻ 0.001). This experiment demonstrates a relationship between gamma oscillatory activity and the metaplasticity of synaptic strength in visual cortex Discussion LTP and LTD may be involved intrinsically in memory processing (ManahanVaughan and Braunewell, 1999;Kemp and Manahan-Vaughan, 2004, 2005Uzakov et al, 2005;Whitlock et al, 2006). Apart from its role in development, the visual cortex has been proposed as a memory system, involved in encoding stimulus features and in the short-term storage of sensory stimuli to guide behavior (Pasternak and Greenlee, 2005).…”

Behavioral tagging is a general mechanism of long-term memory formation

“…In their seminal work they showed that early-LTP, a transient form of LTP that is induced by a weak stimulus, could be extended to late-LTP, a more persistent form of LTP, if the weak and the strong stimuli were applied in a relatively long-lasting associative time window on different synapses of the same neuron. Frey and colleagues also found that an hippocampal LTP can be reinforced by exposing rats to a novelty or to a holeboard training and this phenomenon is protein synthesisdependent (10,11).…”

“…In their seminal work they showed that early-LTP, a transient form of LTP that is induced by a weak stimulus, could be extended to late-LTP, a more persistent form of LTP, if the weak and the strong stimuli were applied in a relatively long-lasting associative time window on different synapses of the same neuron. Frey and colleagues also found that an hippocampal LTP can be reinforced by exposing rats to a novelty or to a holeboard training and this phenomenon is protein synthesisdependent (10,11).Considering that LTP and some forms of LTM share a number of properties, such as associativity, durability and protein synthesis dependence (12), it is feasible that a mechanism of STC, also operates in the formation of LTM.The main goal of the present work is to study the process of behavioral tagging using several combinations of behavioral tasks, to investigate whether a behavioral experience can extend the duration of the memory for an independent task by providing the PRPs needed for its consolidation. We found that the behavioral tagging process operates in different hippocampus-and cerebral cortex-dependent learning tasks, suggesting that it represents a general mechanism of LTM formation.…”