Novelty acquisition is associated with induction of hippocampal long-term depression

Abstract

Homosynaptic long-term depression (LTD) consists of a persistent nonpathological decrease in synaptic transmission, which is induced by low-frequency stimulation. In vivo, low-frequency stimulation (1 Hz, 900 pulses) induces LTD in Wistar but not Hooded Lister rats. In this study, we investigated the influence of behavioral learning and behavioral state on the expression of LTD in both rat strains. Recordings were taken from freely moving animals that had undergone chronic implantation of a recording electrode in the hippocampal CA1 region and a bipolar stimulating electrode in the ipsilateral Schaffer collateral-commissural pathway. Exposure of the rat strains to stress induced a significant elevation in serum corticosterone levels but did not facilitate LTD expression. However, LFS given during exploration of a novel environment resulted in LTD expression in Hooded Lister, and LTD enhancement in Wistar, rats. Reexposure to the same environment did not result in new expression of LTD. Behavioral comparison between the first and second environmental exposure confirmed that the animals had habituated to the novel environment. These observations strongly implicate an association between novelty acquisition and LTD.

Figure 1

LTD expression is strain dependent and is facilitated by novelty exploration. Stable basal synaptic transmission was evoked via stimulation of (a) the ipsilateral pathway and (b) the contralateral pathway in Wistar and Hooded Lister rats by using test-pulses. (c) LFS (1 Hz, 900 pulses) induces LTD in Wistar, but not in Hooded Lister, rats. (d) Test-pulses given to the contralateral pathway during LTD expression on the ipsilateral side confirm the input-specificity of LTD obtained. (e) Novel exposure of Hooded Lister rats to a holeboard during LFS induces robust LTD in this rat strain. LTD was still present 7 d after LFS + holeboard was given. Reexposure of the rats to the holeboard 10–14 d after the first exposure, when fEPSP values had returned to basal levels, did not result in LTD induction by LFS. (f) LTD is enhanced in Wistar rats that underwent novel exposure to a holeboard during LFS. LTD was still present 7 d after LFS + holeboard was given. Reexposure of the rats to the holeboard 10–14 d after the first exposure did not result in LTD facilitation by LFS. (Insets) Field potentials (average of five consecutive sweeps) from typical experiments at the times indicated by the numbers. Horizontal bar = 5 ms; vertical bar = 2 mV. Line-breaks indicate change in time-scale.

Figure 2

LTD facilitation by novelty exploration requires a threshold level of afferent stimulation. (a) Basal synaptic transmission was depressed in the first 90 min in Hooded Lister animals that did not receive LFS but received test-pulse stimulation during novel exposure to the holeboard, whereas Wistar rats exhibited STD that lasted for >3 h. (b) Test-pulse stimulation via the contralateral commissural pathway during novel exposure to the holeboard resulted in STD that lasted 90 min in Hooded Lister rats and <3 h in Wistar rats. (c) A reduction in test-pulse number (to approximately one sweep per hour) after exposure to the holeboard in the presence of basal stimulation curtailed STD in Wistar rats. STD was completely prevented when holeboard exposure was carried out in the absence of test-pulse stimulation (test-pulses were first given 60 min after the holeboard was removed). (d) Test-pulse stimulation given during reexposure to the holeboard 10 −14 d after the first exposure did not result in STD expression in either the Wistar or Hooded Lister strains. (Insets) Field potentials (average of five consecutive sweeps) from typical experiments at the times indicated by the numbers. Horizontal bar = 5 ms; vertical bar = 2 mV. Line breaks indicate change in time scale.

Figure 3

(a) Habituation occurs after reexposure to the holeboard in both Wistar and Hooded Lister rats, and exploratory behavior decreases when novel exposure to the holeboard is followed by reexposure to the same holeboard 10–14 d later. A significant decrease in both rearing (P < 0.05 for both strains) and head-dipping (P < 0.05 for both strains) was seen. A significant difference between the exploratory activity of Wistar compared with Hooded Lister rat strains was also found with regard to rearing (P < 0.05 for both novel exposure and reexposure) and head-dipping (P < 0.01, for both novel exposure and reexposure) (P < 0.05). (b) Serum CORT levels are altered after exposure to different behavioral challenges. A significant increase in serum CORT levels, compared with basal values, was seen when Wistar rats were exposed to either a novel holeboard (P < 0.05), an unfamiliar environment (P < 0.05), or an elevated platform (P < 0.001). Similarly, a significant increase in CORT, compared with basal values, was seen when Hooded Lister rats were exposed to either a novel holeboard (P < 0.05), an unfamiliar environment (P < 0.05), or an elevated platform (P < 0.01). The platform-evoked CORT elevation was significantly different from holeboard-induced levels in both strains (P < 0.01 Wistar, P < 0.05 Hooded Lister). Hooded Lister rats had significantly lower basal levels of CORT than Wistar rats (P < 0.05).

Figure 4

LTP is reversed by novelty exploration. High-frequency stimulation at 100 Hz induces long-term potentiation in (a) Wistar (n = 6) and (b) Hooded Lister rat strains. Exposure of the animals to a novel holeboard 60 min after induction of LTP resulted in reversal of LTP to basal values in both Wistar (a, P < 0.001) and Hooded Lister Wistar (b, P < 0.001) rats. (c) LTD is not facilitated by stress. Placement of recording-naive Hooded Lister or Wistar rats in an unfamiliar brightly lit recording chamber, followed 30 min later by LFS, does not facilitate LTD induction. (Insets) Field potentials (average of five consecutive sweeps) from typical experiments at the times indicated by the numbers. Horizontal bar = 5 ms; vertical bar = 2 mV. Line-breaks indicate change in time scale.