Performance on the task depended on both circadian time and sex, with memory enhanced at night in males but during the day in females.
Long-term synaptic potentiation magnitude at CA3-CA1 synapses was greater at night compared to day for both sexes.
Spontaneous synaptic inhibition frequency and amplitude were higher during the day regardless of sex.
Females exhibited larger spontaneous synaptic excitation compared to males, independent of time-of-day.
CA1 pyramidal neurons showed enhanced excitability at night, influenced by synaptic excitation and inhibition.
The study highlights the impact of sex and circadian time on hippocampal neurophysiology.
Simplified
Circadian rhythms are biological processes that cycle across 24 h and regulate many facets of neurophysiology, including learning and memory. Circadian variation in spatial memory task performance is well documented; however, the effect of sex across circadian time (CT) remains unclear. Additionally, little is known regarding the impact of time-of-day on hippocampal neuronal physiology. Here, we investigated the influence of both sex and time-of-day on hippocampal neurophysiology and memory in mice. Performance on the (OLM) task depended on both circadian time and sex, with memory enhanced at night in males but during the day in females. Long-term synaptic potentiation () magnitude at CA3-CA1 synapses was greater at night compared with day in both sexes. Next, we measured spontaneous synaptic excitation and inhibition onto CA1 pyramidal neurons. Frequency and amplitude of inhibition was greater during the day compared with night, regardless of sex. Frequency and amplitude of excitation was larger in females, compared with males, independent of time-of-day, although both time-of-day and sex influenced presynaptic release probability. At night, CA1 pyramidal neurons showed enhanced excitability (action potential firing and/or baseline potential) that was dependent on synaptic excitation and inhibition, regardless of sex. This study emphasizes the importance of sex and time-of-day in hippocampal physiology, especially given that many neurologic disorders impacting the hippocampus are linked to circadian disruption and present differently in men and women. Knowledge about how sex and circadian rhythms affect hippocampal physiology can improve the translational relevancy of therapeutics and inform the appropriate timing of existing treatments.
Key numbers
0.028
Males outperform females in at night
p-value from two-way ANOVA for male performance at night vs. day.
0.003
magnitude at night vs. day
p-value from three-way RM-ANOVA comparing magnitude.
0.008
Inhibitory synaptic transmission amplitude during day vs. night
p-value from GEE analysis of sIPSC amplitude.
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