Circadian regulation of hippocampal long-term potentiation

Abstract

The goal of this study is to investigate the possible circadian regulation of hippocampal excitability and long-term potentiation (LTP) measured by stimulating the Schaffer collaterals (SC) and recording the field excitatory postsynaptic potential (fEPSP) from the CA1 dendritic layer or the population spike (PS) from the soma in brain slices of C3H and C57 mice. These 2 strains of mice were of interest because the C3H mice secrete melatonin rhythmically while the C57 mice do not. The authors found that the magnitude of the enhancement of the PS was significantly greater in LTP recorded from night slices compared to day slices of both C3H and C57 mice. They also found significant diurnal variation in the decay of LTP measured with fEPSPs, with the decay slower during the night in both strains of mice. There was evidence for a diurnal rhythm in the input/output function of pyramidal neurons measured at the soma in C57 but not C3H mice. Furthermore, LTP in the PS, measured in slices prepared during the day but recorded during the night, had a profile remarkably similar to the night group. Finally, PS recordings were carried out in slices from C3H mice maintained in constant darkness prior to experimentation. Again, the authors found that the magnitude of the enhancement of the PS was significantly greater in LTP recorded from subjective night slices compared to subjective day slices. These results provide the 1st evidence that an endogenous circadian oscillator modulates synaptic plasticity in the hippocampus.

Figure 1

Schematic of experimental design. (A) Schematic of the hippocampus, illustrating electrode placement for stimulating as well as recording electrodes. (B) Examples of a field excitatory postsynaptic potential (fEPSP) and population spike (PS) before and after tetanus. (C) Experimental design in which day/night comparisons were made by preparing brain slices at ZT 3 and recording between ZT 4–10 (day) or preparing tissue at ZT 15 and recording between ZT 16–22 (night).

Figure 2

Diurnal variation in long-term potentiation (LTP) measured in the cell body region of CA1 neurons in C3H and C57 mice. (A) Plots of population spike (PS) slope (normalized as a percentage of baseline) as a function of time measured in the day and night in C3H mice. (B) Plots of PS slope (normalized as a percentage of baseline) as a function of time measured in the day and night in C57 mice. The tetanus of 1 × 100-Hz stimulation was given at time = 0.

Figure 3

Input/output (I/O) curves illustrating the relationship between the magnitudes of stimulation current and evoked response for the population spike (PS) recorded from C3H (A) and C57 (B) mice. The C3H mice did not exhibit a day/night difference in I/O curves measured for the PS (A). In contrast, the I/O curves for the PS recorded in the night from C57 mice were significantly larger then the I/O curves recorded in the day (B). The magnitude of the PS was larger in the night at each of the stimulus intensities between 30 and 100 μA. No diurnal differences were found in the I/O curves measured from the field excitatory postsynaptic potential (fEPSP) of C3H or C57 mice (data not shown).

Figure 4

Endogenous rhythms recorded from isolated hippocampal slices. (A) C3H mice were kept in an LD cycle and killed in the day (1 h prior to lights-off at ZT 11), and evoked responses were recorded at night (from ZT 13–18). The population spike (PS) long-term potentiation (LTP) of slices prepared during the day but recorded during the night had the profile remarkably similar to the night group. Similar results were obtained with the field excitatory postsynaptic potential (fEPSP) recordings (data not shown). (B) Animals were maintained in DD, and the onset of activity was taken as CT 12. Plots of PS slope (normalized as a percentage of baseline) as a function of time were measured in the subjective day and subjective night. The PS LTP was larger in the subjective night. For both sets of experiments, the tetanus of 1 ×100-Hz stimulation was given at time = 0.