Hippocampal long-term depression and long-term potentiation encode different aspects of novelty acquisition

Abstract

The hippocampus is required for encoding spatial information. Little is known however, about how different attributes of learning are related to different types of synaptic plasticity. Here, we investigated the association between long-term depression (LTD) and long-term potentiation, both cellular models for learning, and novelty exploration. We found that exploration of a new environment containing unfamiliar objects and/or familiar objects in new locations facilitated LTD, whereas exploration of the new environment itself, in the absence of objects, impaired LTD. Furthermore, we found this phenomenon to be modulated by 5-hydroxytryptamine 4 receptor activation. In contrast, long-term potentiation was facilitated by exploration of an empty novel environment, but simultaneous object exploration caused depotentiation. We also found that no further LTD could be induced. These findings support a decisive role for LTD in the acquisition of object-place configuration and consolidate its candidacy as a learning mechanism.

Fig. 1.

LFS does not induce LTD. (a) Application of LFS (arrow) induced short-term depression compared with test-pulse stimulated controls. Line breaks indicate changes in time scale. (b) Analog traces of averaged fEPSPs taken at t =–5 min, t = 5 min, and t = 24 h after LFS. (Upper) Baseline controls. (Lower) An LFS experiment. Vertical scale bar corresponds to 0.5 mV, and horizontal bar corresponds to 5 ms.

Fig. 2.

Exposure to a novel holeboard with objects facilitates LTD. (a) LFS given simultaneously with holeboard exposure (indicated by black box) facilitated LTD upon first-time exposure (□) or if the objects were repositioned (▴). No facilitation occurred upon reexposure to the holeboard containing the same object configuration as in the first exposure (▪). (b) Analog traces representing novelty exploration (Top), reexposure (Middle), and novel object configuration (Bottom). They illustrate (from right to left) levels before LFS, after LFS, and 24 h after LFS. Vertical scale bar corresponds to 0.5 mV, and horizontal bar corresponds to 5 ms.

Fig. 3.

Exploration of empty holeboard inhibits LTD. (a) Concurrent with LFS, the animals were either exposed to an empty holeboard (white box) or a holeboard containing objects (black box). (b) Analog traces (Upper) represent levels before, after, and 24 h after LFS from a rat exposed to the empty holeboard. (Lower) Traces recorded from an experiment with an object-containing holeboard. Vertical scale bar corresponds to 0.5 mV, and horizontal bar corresponds to 5 ms.

Fig. 4.

Exploration of empty holeboard facilitates LTP. (a) Weak HFT (100 pulses at 100 Hz) given at the time point indicated by the arrow induces short-term potentiation. Weak HFT given at the beginning of 15 min of empty holeboard exploration (white box) facilitates short-term potentiation into LTP. (b) Analog traces (Upper) represent potentials recorded before HFT, 20 min after HFT, and 24 h after HFT, in an HFT experiment. (Lower) fEPSPs observed before HFT, 5 min after holeboard removal (i.e., 20 min after HFT), and 24 h after HFT. Vertical scale bar corresponds to 0.5 mV, and horizontal bar corresponds to 5 ms.

Fig. 5.

LTP is depotentiated by object exploration. (a) LTP was induced by strong HFT (4 trains of 30 pulses at 100 Hz with 5-min intertrain intervals, downward arrow) in animals in a familiar recording chamber. Exploration of a novel object-containing holeboard depotentiated LTP (▪). LFS applied 120 min after HFT (indicated by dashed upward arrow) did not elicit any synaptic depression (▴). (b) Analog traces (Upper) represent fEPSPs from an experiment without holeboard exploration before HFT, after HFT, and 24 h after HFT. (Lower) Analogs obtained at similar time points when novel exploration had occurred. Vertical scale bar corresponds to 0.5 mV, and horizontal bar corresponds to 5 ms.

Fig. 6.

RS67333 inhibits exploration-induced LTD and habituation to novel holeboard. (a) LFS applied under novel exploration induced LTD when animals were injected with saline but not when injected with 10 μg of RS67333. (b) Reexposure to the holeboard. Both groups were injected with saline, as indicated by arrow. The animals that were injected with RS67333 before first exposure now expressed LTD after LFS. The vehicle group did not express LTD. (c) Habituation test in large holeboard. (i) Number of rears in animals injected with 10 μg of RS67333 (drug) or with saline (control). White bars comprise data from first exposure, and black bars are from reexposure 24 h later. (ii) Number of dips recorded in the same experiment as above. (d) Analog traces obtained before LFS, after LFS, and 24 h after LFS. (i) Experiment shown in a. (Upper) Vehicle experiment. (Lower) Injection of RS67333. (ii) Traces comprise the corresponding analogs from the experiment shown in b. Vertical scale bar corresponds to 0.5 mV, and horizontal bar corresponds to 5 ms.