Dorsal CA1 interneurons contribute to acute stress-induced spatial memory deficits

Abstract Exposure to severely stressful experiences disrupts the activity of neuronal circuits and impairs declarative memory. GABAergic interneuronscoordinate neuronal network activity, but their involvement in stress-evoked memory loss remains to be elucidated. Here, we provide evidence that interneuronsin area CA1 of the dorsal hippocampus partially modulate acute stress-induced memory deficits. In adult male mice, both acute forced swim stress and restraint stress impaired hippocampus-dependent spatial memoryand increased the density of c-fos-positive interneuronsin the dorsal CA1. Selective activation of dorsal CA1 interneuronsby chemogeneticsdisrupted memory performance in the spatial object recognition task. In comparison, anxiety-related behavior, spatial working memory and novel object recognition memoryremained intact when dorsal CA1 interneuronswere overactivated. Moreover, chemogeneticactivation of dorsal CA1 interneuronssuppressed the activity of adjacent pyramidal neurons, whereas a single exposure to forced swim stress but not restraint stress increased the activity of CA1 pyramidal neurons. However, chemogeneticinhibition of dorsal CA1 interneuronsled to spatial memoryimpairments and failed to attenuate acute stress-induced memory loss. These findings suggest that acute stress may overactivate interneuronsin the dorsal CA1, which reduces the activity of pyramidal neurons and in turn disrupts long-term memory.