Impaired hippocampal place cell dynamics in a mouse model of the 22q11.2 deletion

Using two-photon Ca 2+ imaging in hippocampal area CA1 of Df(16)A +/− mice, an animal model of 22q11.2 deletion syndrome, the authors found a reduction in spatial map stability compared to that in wild-type mice, as well as an absence of goal-directed place cell reorganization during goal-oriented spatial learning. Hippocampal place cells represent the cellular substrate of episodic memory. Place cell ensembles reorganize to support learning but must also maintain stable representations to facilitate memory recall. Despite extensive research, the learning-related role of place cell dynamics in health and disease remains elusive. Using chronic two-photon Ca 2+ imaging in hippocampal area CA1 of wild-type and Df(16)A +/− mice, an animal model of 22q11.2 deletion syndrome, one of the most common genetic risk factors for cognitive dysfunction and schizophrenia, we found that goal-oriented learning in wild-type mice was supported by stable spatial maps and robust remapping of place fields toward the goal location. Df(16)A +/− mice showed a significant learning deficit accompanied by reduced spatial map stability and the absence of goal-directed place cell reorganization. These results expand our understanding of the hippocampal ensemble dynamics supporting cognitive flexibility and demonstrate their importance in a model of 22q11.2-associated cognitive dysfunction.