Abstract
Chronic uncontrollable stress has been shown to produce various physiological alterations and impair mnemonic functions in the rodent hippocampus. Impacts on neuronal activities, however, have not been well investigated. The present study examined dorsal CA1 place cells to elucidate the computational changes associated with chronic stress effects on cognitive behaviors. After administering chronic restraint stress (CRS; 6 hours/day for ≥21 consecutive days) to adult male mice, several hippocampal characteristics were examined; i.e., spatial learning, in vitro synaptic plasticity, in vivo place cell recording, and western blot analysis to determine protein levels related to learning and memory. Behaviorally, CRS significantly impeded spatial learning but enhanced non-spatial cue learning on the Morris water maze. Physiologically, CRS reduced long-term potentiation (LTP) of Schaffer collateral/commisural-CA1 pathway, phospho-αCaMKII (alpha Ca2+/calmodulin-dependent protein kinase II) level in the hippocampus, and stability of spatial representation and the mean firing rates (FRs) of place cells. Moreover, the local cue-dependency of place fields was increased, and the intra-burst interval (IntraBI) between consecutive spikes within a burst was prolonged following CRS. These results extend the previous findings of stress impairing LTP and spatial learning to CRS modifying physical properties of spiking in place cells that contribute to changes in navigation and synaptic plasticity.
Highlights
The hippocampus is crucial for the formation of long-term declarative memory in humans and spatial memory in rodents[1,2,3,4]
With chronic stress, morphological changes, suppression of adult neurogenesis, and neuronal endangerment have been observed in the hippocampus[19,20]
We investigated several neurophysiological effects of chronic restraint stress (CRS) in mice (Fig. S1), and report that the same stress that impaired spatial learning and long-term potentiation (LTP) decreased the stability of place fields, the mean firing rates (FRs) and the phospho-α CaMKII level, altered the bursting pattern of place cells, and shifted the place fields’ dependency from spatial cues to local cues
Summary
The hippocampus is crucial for the formation of long-term declarative (or explicit) memory in humans and spatial (or relational) memory in rodents[1,2,3,4]. With chronic stress (e.g., recurrent restraint across days), morphological changes (e.g., dendritic retraction), suppression of adult neurogenesis, and neuronal endangerment have been observed in the hippocampus[19,20]. An earlier study found that following an acute audiogenic stress (2 h) experience, rats exhibited decreases in spatial correlation and stable firing pattern in their place cells[25]. We investigated several neurophysiological effects of CRS in mice (Fig. S1), and report that the same stress that impaired spatial learning and LTP decreased the stability of place fields, the mean FR and the phospho-α CaMKII level, altered the bursting pattern of place cells, and shifted the place fields’ dependency from spatial cues to local cues
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