Histone deacetylase inhibition facilitates massed pattern-induced synaptic plasticity and memory

Abstract

Massed training is less effective for long-term memory formation than the spaced training. The role of acetylation in synaptic plasticity and memory is now well established. However, the role of this important protein modification in synaptic plasticity induced by massed pattern of stimulation or memory induced by massed training is not well understood. Here we show that increasing the level of acetylation enhances long-term potentiation induced by massed pattern of high frequency stimulation. Furthermore, enhancing acetylation level facilitates long-term memory by massed training. Thus, increasing acetylation level facilitates synaptic plasticity and memory by massed patterns.

Figure 1.

Pattern sensitivity of long-term potentiation (LTP) and the effect of histone deacetylase inhibition on massed pattern-induced LTP. (A) Spaced tetanic stimuli induce higher extent of LTP than massed tetanic stimuli. The slices were given four bursts (each burst consisted of 100 stimuli at 100 Hz) of stimulation with inter-burst interval of either 5 min (Spaced) or 20 sec (Massed). Both stimulation paradigms induced synaptic potentiation that lasted for at least 109 min. However, LTP induced by spaced tetanic stimulation was higher in magnitude than the LTP induced by massed tetanic stimulation (n = 5, both groups). The recording traces before (−2 min) and after (109 min) first stimulation in spaced (a) and massed (b) conditions are also shown. (B) Histone deacetylase inhibition enhances LTP by massed tetanic stimulation. LTP was induced by four bursts (each burst consisted of 100 stimuli at 100 Hz) of stimulation with 20-sec inter-burst interval in the presence or absence of histone deacetylase inhibitor, sodium butyrate (SB). SB enhanced LTP induced by massed tetanic stimulation (n = 5, both groups). Recording traces before (−2 min) and after (58 min) first tetanic stimulation in the absence (a) or presence (b) of SB are also shown.

Figure 2.

Performance of massed- and spaced-trained animals in the water maze task. (A) The animals were given either spaced or massed training (n = 11, both groups) in the water maze. The inter-block interval in the spaced group was 2 h and inter-block interval in the massed group was 1 min. Each block consisted of 5 trials with 1 min inter-trial interval. Spaced- as well as massed-trained animals showed decrease in latency to reach the platform over the course of training. During the long-term memory test (LTM test), the spaced-trained animals took significantly less time to reach the platform area than the massed-trained animals. Average of five trials is plotted for each block. (B) The animals that received spaced training spent significantly more time in the platform quadrant (Q4) than the massed-trained animals during the long-term memory test (LTM test in A). (C) The spaced-trained animals showed significantly more annulus crossings than the massed-trained animals during the long-term memory test (LTM test in A). (D) The representative track plots during the long-term memory test (LTM test in A) are shown for both groups. Asterisks denote significant difference (P < 0.05).

Figure 3.

Sodium butyrate (SB) facilitates long-term memory formation by massed training. The animals were given massed training in the water maze task. (A) Both groups (SB + massed-trained, n = 13; massed-trained, n = 15) showed reduction in escape latency over the course of training. During the long-term memory test (LTM test), the SB + massed-trained animals reached the platform area sooner than the massed-trained animals. (B) During the long-term memory test (LTM test in A), the time spent in different quadrants (Q4 = platform quadrant) is shown for massed-trained and SB + massed-trained animals. (C) During the long-term memory test (LTM test in A), the SB + massed-trained animals showed significantly more annulus crossings than massed-trained animals. (D) The representative track plots during the long-term memory test (LTM test in A) are shown for both groups. Asterisks denote significant difference (P < 0.05).