Abstract
Rewiring neural circuits by the formation and elimination of synapses is thought to be a key cellular mechanism of learning and memory in the mammalian brain. Dendritic spines are the postsynaptic structural component of excitatory synapses, and their experience-dependent plasticity has been extensively studied in mouse superficial cortex using two-photon microscopy in vivo. By contrast, very little is known about spine plasticity in the hippocampus, which is the archetypical memory center of the brain, mostly because it is difficult to visualize dendritic spines in this deeply embedded structure with sufficient spatial resolution. We developed chronic 2P-STED microscopy in mouse hippocampus, using a 'hippocampal window' based on resection of cortical tissue and a long working distance objective for optical access. We observed a two-fold higher spine density than previous studies and measured a spine turnover of ~40% within 4 days, which depended on spine size. We thus provide direct evidence for a high level of structural rewiring of synaptic circuits and new insights into the structure-dynamics relationship of hippocampal spines. Having established chronic super-resolution microscopy in the hippocampus in vivo, our study enables longitudinal and correlative analyses of nanoscale neuroanatomical structures with genetic, molecular and behavioral experiments.
Highlights
Dendritic spines form the postsynaptic structural component of most excitatory synapses in the mammalian brain
Spine structure is closely linked to synapse function, as the size of spine heads scales with synaptic strength (Matsuzaki et al, 2001; Noguchi et al, 2011) and the shape and number of spines can be modified by the induction of synaptic plasticity (Matsuzaki et al, 2001; Engert and Bonhoeffer, 1999; Nagerl et al, 2004; Tønnesen et al, 2014; Zhou et al, 2004) and by sensory experience (Holtmaat et al, 2006; Keck et al, 2011)
We set up in vivo stimulated emission depletion (STED) microscopy of dendritic spines in mouse hippocampus to track their morphological dynamics over the course of several days
Summary
Dendritic spines form the postsynaptic structural component of most excitatory synapses in the mammalian brain. They constitute computational units of information processing that underlie essentially all higher brain functions (Nimchinsky et al, 2002; Sala and Segal, 2014; Yuste and Bonhoeffer, 2004) and play a crucial role in brain disorders such as autism spectrum disorder and Alzheimer’s disease (Dorostkar et al, 2015; Sudhof, 2008). Rewiring of neural circuits by spine plasticity is considered a key neurobiological mechanism of memory formation (reviewed in [Nimchinsky et al, 2002; Sala and Segal, 2014; Yuste and Bonhoeffer, 2004; Kasai et al, 2010]).
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