1 Department of Anesthesia and.
2 School of Human Nutrition, McGill University, Montreal, Canada.
3 Department of Neurosciences, Center for Interdisciplinary Research on Brain and Learning (CIRCA) and Research Group on Neural Signaling and Circuitry (GRSNC), Université de Montréal, Montreal, Canada.
4 Department of Biochemistry, McGill University, Montreal, Canada.
5 Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
6 Montreal Neurological Institute.
7 Department of Psychology, Faculty of Science, and.
8 Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.
9 Biomedical Research Institute, Foundation for Research and Technology-Hellas, University Campus, Ioannina, Greece.
10 Department of Psychology/Centre for Studies in Behavioural Neurobiology, Concordia University, Montreal, Canada.
11 Department of Physiology and.
12 Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, Canada.

Repeated or prolonged, but not short-term, general anesthesia during the early postnatal period causes long-lasting impairments in memory formation in various species. The mechanisms underlying long-lasting impairment in cognitive function are poorly understood. Here, we show that repeated general anesthesia in postnatal mice induces preferential apoptosis and subsequent loss of parvalbumin-positive inhibitory interneurons in the hippocampus. Each parvalbumin interneuron controls the activity of multiple pyramidal excitatory neurons, thereby regulating neuronal circuits and memory consolidation. Preventing the loss of parvalbumin neurons by deleting a proapoptotic protein, mitochondrial anchored protein ligase (MAPL), selectively in parvalbumin neurons rescued anesthesia-induced deficits in pyramidal cell inhibition and hippocampus-dependent long-term memory. Conversely, partial depletion of parvalbumin neurons in neonates was sufficient to engender long-lasting memory impairment. Thus, loss of parvalbumin interneurons in postnatal mice following repeated general anesthesia critically contributes to memory deficits in adulthood.