The dynamic impact of repeated stress on the hippocampal spatial map

Abstract

Stress alters the function of many physiological processes throughout the body, including in the brain. A neural circuit particularly vulnerable to the effects of stress is the hippocampus, a key component of the episodic and spatial memory system in both humans and rodents. Earlier studies have provided snapshots of morphological, molecular, physiological and behavioral changes in the hippocampus following either acute or repeated stress. However, the cumulative impact of repeated stress on in vivo hippocampal physiology remains unexplored. Here we report the stress-induced modulation of the spatially receptive fields of the hippocampal CA1 'place cells' as mice explore familiar and novel tracks after 5 and 10 days of immobilization stress. We find that similar to what has been observed following acute stress, five days of repeated stress results in decreased excitability of CA1 pyramidal cells. Following ten days of chronic stress, however, this decreased hippocampal excitability is no longer evident, suggesting adaptation may have occurred. In addition to these changes in neuronal excitability, we find deficient context discrimination, wherein both short-term and chronic stress impair the ability of the hippocampus to unambiguously distinguish novel and familiar environments. These results suggest that a loss of network flexibility may underlie some of the behavioral deficits accompanying chronic stress.

Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man

“…Research with rodents and nonhuman primates also demonstrates that exposure to an acute, uncontrollable stress impairs performance in cognitive and memory tasks that depend heavily on the PFC 90 . For example, restraint-stressed rats display impaired performance in a delayed spatial alternation task, a rodent behavioural test of spatial working memory 91 .…”

Synaptic Loss and the Pathophysiology of PTSD: Implications for Ketamine as a Prototype Novel Therapeutic

“…While some studies do not report altered neural excitability in association hippocampal dendritic atrophy produced by chronic stress [69, 73], other studies report increases in neural excitability [74]. The latter have informed a computational hippocampal network model in which dendritic atrophy produces increased excitability that impairs neuroplasticity by saturating long-term potentiation [75].…”

Chronic Stress Alters Spatial Representation and Bursting Patterns of Place Cells in Behaving Mice

“…The extent of chronic stress influences on place cells has just begun to be studied. A very recent study found that restraining mice 2 h/d for 5 consecutive days (but not 10 consecutive days due to adaptation) caused significant decreases in firing rates and field sizes of place cells 27 . However, this study focused exclusively on the place cell properties; whether the same stress affected other hippocampal functions, such as spatial learning and synaptic plasticity, are unknown.…”