Circadian modulation of neurons and astrocytes controls synaptic plasticity in hippocampal area CA1

Abstract

Most animal species operate according to a 24-hour period set by the suprachiasmatic nucleus (SCN) of the hypothalamus. The rhythmic activity of the SCN is known to modulate hippocampal-dependent memory processes, but the molecular and cellular mechanisms that account for these effects remain largely unknown. Here, we show that there are cell-type specific structural and functional changes that occur with circadian rhythmicity in neurons and astrocytes in hippocampal area CA1. Pyramidal neurons change the surface expression of NMDA receptors, whereas astrocytes change their proximity to synapses. Together, these phenomena alter glutamate clearance, receptor activation and integration of temporally clustered excitatory synaptic inputs. These findings identify important mechanisms through which neurons and astrocytes modify the molecular composition and structure of the synaptic environment, contribute to the local storage of information in the hippocampus and alter the temporal dynamics of learning and memory processing.

Bmal1‐deficiency affects glial synaptic coverage of the hippocampal mossy fiber synapse and the actin cytoskeleton in astrocytes

“…This adds to increasing evidence that chronodisruption in general affects brain structure and function by compromising not only neurons but also glia cells. Recently, it was observed that glial coverage of the synapses in CA1 shows circadian changes, whereby the number of fine astrocytic processes decreases during the dark phase (McCauley et al, 2019). Therefore, Bmal1, as a core clock component, could be involved in the circadian modulation of the fine astrocytic processes.…”

cFos Ensembles in the Dentate Gyrus Rapidly Segregate Over Time and do not Form a Stable Map of Space

“…These observations and our data suggest that the temporal shift in ensemble selection occurs even when the spatial context remains the same. Thus, cFos is not only an indicator of intense neuronal activity but also reflects a clock signal 6,45 that is crucial for LTP, perhaps selecting a specific subset of neurons for memory storage. Our results support the concept that cFos+ neurons in DG encode an episode, but not a spatial position 46 .…”

“…How time is represented in the hippocampus is still incompletely understood. Many genes affecting synaptic plasticity undergo pronounced circadian oscillations, changing the rules of synaptic plasticity depending on the time of day 6 . Theoretical and empirical work suggests that the dentate gyrus (DG) actively reduces the overlap of activity patterns coming from entorhinal cortex [7][8][9] .…”

A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics

“…Figure 6-Figure Supplement 2 shows multiple aspects related to temperature in STDP experiments and the temperature and age choices for the publications described in Table 1 compared to physiological conditions. We estimate how the rat’s body temperature physiologically evolves in function of age using McCauley et al (2020) and Wood et al (2016) data.…”