Long-Term Potentiation in Direct Perforant Path Projections to the Hippocampal CA3 Region In Vivo

108

The induction of long-term potentiation (LTP) in the hippocampal formation can be modulated by different behavioral states. However, few studies have addressed modulation of LTP during behavioral states in which the animal is likely acquiring new information. Here, we demonstrate that both the induction and the longevity of LTP in the dentate gyrus are enhanced when LTP is induced during the initial exploration of a novel environment. These effects are independent from locomotor activity, changes in brain temperature, and theta rhythm. Previous exposure to the novel environment attenuated this enhancement, suggesting that the effects of novelty habituate with familiarity. LTP longevity also was enhanced when induced in familiar environments containing novel objects. Together, these data indicate that both LTP induction and maintenance are enhanced when LTP is induced while rats investigate novel stimuli. We suggest that novelty initiates a transition of the hippocampal formation to a mode that is particularly conducive to synaptic plasticity, a process that could allow for new learning while preserving the stability of previously stored information. In addition, LTP induced in novel environments elicited a sustained late LTP. This suggests that a single synaptic population can display distinct profiles of LTP maintenance and that this depends on the animal's behavioral state during its induction. Furthermore, the duration of LTP enhanced by novelty parallels the time period during which the hippocampal formation is thought necessary for memory, consistent with the view that dentate LTP is of a duration sufficient to sustain memory in the hippocampal formation.

Section: Discussionsupporting

confidence: 75%

Novel Environments Enhance the Induction and Maintenance of Long-Term Potentiation in the Dentate Gyrus

Davis¹,

Jones²,

Derrick³

2004

108

“…Homosynaptic LTP-heterosynaptic LTDs have been observed previously in the CA1 (Lynch et al, 1977;Dunwiddie and Lynch, 1978), CA3 (Bradler and Barrioneuvo, 1989;Martinez et al, 2002), and dentate gyrus (Levy and Steward, 1979;Abraham and Goddard, 1983) regions of the hippocampus, in the cortex (Tsumoto and Suda, 1979;Hirsch et al, 1992), and in cultured neuromuscular junctions (Lo and Poo, 1991). In addition, homosynaptic LTP at the T-S synapse is NMDAR independent, a trait that is also observed in the LTP found in various regions of the mammalian brain (Nicoll and Malenka, 1995;Salin et al, 1996;Do et al, 2002a). One surprising feature about the T-S synapse is that although homosynaptic LTP is NMDAR independent, heterosynaptic LTD required NMDAR activity, the reverse of what is typically observed (for review, see Linden and Connor 1995).…”

Section: Homosynaptic Ltp-heterosynaptic Ltd At the T-s Synapsesupporting

confidence: 54%

Multiple Forms of Long-Term Potentiation and Long-Term Depression Converge on a Single Interneuron in the Leech CNS

Burrell¹,

Sahley²

2004

Long-term potentiation (LTP) of synaptic transmission was observed in two types of synapses that converge on the same postsynaptic neuron in the leech CNS. These synapses were made by identifiable sensory neurons, the mechanosensory touch (T-) and pressure (P-) cells, onto the S-cell, an interneuron critical for certain forms of learning. Changes in both the T-S and P-S synapses appear to be activity dependent because LTP was restricted to inputs that had undergone tetanization; however, properties of synaptic plasticity at the T-S and P-S connections differ considerably. At the P-S synapse, LTP was induced in the tetanized synapse but not in the nontetanized synapse tested in parallel. P-S LTP was blocked by the NMDA receptor antagonist DL-2-amino-5-phosphono-valeric acid (AP-5) or by lowering the extracellular concentration of glycine, an NMDA receptor (NMDAR) co-agonist. P-S LTP was strongly affected by the initial amplitude of the synaptic potential at the time LTP was induced. Smaller amplitude synapses (Ͻ3.5 mV) underwent robust potentiation, whereas the less common, larger amplitude synapse (Ͼ3.5 mV) depressed after tetanization. At the T-S synapse, tetanization simultaneously induced homosynaptic LTP in the tetanized input and heterosynaptic long-term depression (LTD) in the input made by a nontetanized T-cell onto the same S-cell. Interestingly, AP-5 failed to block homosynaptic LTP at the T-S synapse but did prevent heterosynaptic LTD. T-S LTP was not affected by the initial EPSP amplitude. Thus, leech neurons exhibit synaptic plasticity with properties similar to LTP and LTD found in the vertebrate nervous system.

“…Studies have demonstrated that direct projection from the perforant path to CA3 mediates distinct and essential functions (Marr, 1971;Morris and Mcnaughton, 1987), and plasticity induced in the direct perforant path-CA3 projection during learning serves subsequently as the primary input for memory (Treves and Rolls, 1994). Associative LTP can be induced in the perforant path-CA3 pathway, and this form of LTP plays an important role in the hippocampal information processing (Berger and Yeckel, 1991;Do et al, 2002). This summing-up evidence directed us to the design of the LTP study as shown in Figure 1 A.…”

Section: Discussionmentioning

confidence: 99%

Activation of Glycogen Synthase Kinase-3 Inhibits Long-Term Potentiation with Synapse-Associated Impairments

Zhu

Wang²,

Liú³

et al. 2007

214

165

Activation of glycogen synthase kinase-3 (GSK-3) can cause memory deficits as seen in Alzheimer's disease, the most common ageassociated dementia, but the mechanism is not understood. Here, we found that activation of GSK-3 by wortmannin or transient overexpression of wild-type GSK-3␤ could suppress the induction of long-term potentiation (LTP) in rat hippocampus, whereas simultaneous inhibition of GSK-3 by lithium or SB216763 or transient expression of a dominant-negative GSK-3␤ mutant (dnGSK-3␤) preserved the LTP. After high-frequency stimulation (HFS), the presynaptic release of glutamate and the expression/clustering of synapsin I, a synaptic vesicle protein playing an important role in neurotransmitter release, decreased markedly after upregulation of GSK-3. In vitro studies further demonstrated that GSK-3 inhibited the expression of SynI independent of HFS. In postsynaptic level, the expression of PSD93 and NR2A/B proteins decreased significantly when GSK-3 was activated. The LTP-associated synapse impairments including less presynaptic active zone, thinner postsynaptic density, and broader synaptic cleft were also prominent in the hippocampal slices after HFS with activation of GSK-3. These synaptic impairments were attenuated when GSK-3 was simultaneously inhibited by LiCl or SB216763 or transient expression of dnGSK-3. We conclude that upregulation of GSK-3 impairs the synaptic plasticity both functionally and structurally, which may underlie the GSK-3-involved memory deficits.