Abstract
Adverse effects of chronic stress include anxiety, depression, and memory deficits. Some of these stress-induced behavioural deficits are mediated by impaired hippocampal function. Much of our current understanding about how stress affects the hippocampus has been derived from post-mortem analyses of brain slices at fixed time points. Consequently, neural signatures of an ongoing stressful experiences in the intact brain of awake animals and their links to later hippocampal dysfunction remain poorly understood. Further, no information is available on the impact of stress on sharp-wave ripples (SPW-Rs), high frequency oscillation transients crucial for memory consolidation. Here, we used in vivo tetrode recordings to analyze the dynamic impact of 10 days of immobilization stress on neural activity in area CA1 of mice. While there was a net decrease in pyramidal cell activity in stressed animals, a greater fraction of CA1 spikes occurred specifically during sharp-wave ripples, resulting in an increase in neuronal synchrony. After repeated stress some of these alterations were visible during rest even in the absence of stress. These findings offer new insights into stress-induced changes in ripple-spike interactions and mechanisms through which chronic stress may interfere with subsequent information processing.
Highlights
The hippocampus is a medial temporal lobe structure that is crucial for encoding, updating and retrieving episodic memories (Eichenbaum, 2017; Tulving, 1985)
The level of statistical significance was set to 0.05 and p values are shown as follows: *p < 0.05; **p < 0.01; ***p < 0.001. This was designed as a longitudinal study, with recordings from the same cohort of mice during both rest and stress at acute and chronic time points providing samples from each mouse in a single group of animals across time and state
We employed a 10-day chronic immobilization stress (CIS) paradigm (Fig. 1A), that has been previously used to examine the effects of chronic stress on hippocampal memory, volume and CA1 spatial coding (Rahman et al, 2016; Tomar et al, 2015)
Summary
The hippocampus is a medial temporal lobe structure that is crucial for encoding, updating and retrieving episodic memories (Eichenbaum, 2017; Tulving, 1985). Stress-induced changes in the rodent hippocampus include decrease in hippocampal volume (Schoenfeld et al, 2017) shrinkage and debranching of pyramidal cell dendrites, (Sousa et al, 2000), loss of dendritic spines (Magarinos et al, 1997; Sandi et al, 2003), and alterations in synaptic plasticity mecha nisms, including long-term potentiation (Alfarez et al, 2003; Shors et al, 1989). Together, these stress phenotypes at the cellular and syn aptic levels are thought to contribute to impairments in hippocampus-dependent behaviour including learning and memory. Relatively little is known about how the intact, drug-free hippocampus is involved in the quick appraisal of an ongoing stressful situation (Cadle and Zoladz, 2015; Joels, 2009)
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