Adult newborn neurons interfere with fear discrimination in a protocol‐dependent manner

Introduction Significant enhancement of neurogenesis is known to occur in response to a variety of brain insults such as traumatic brain injury. Previous studies have demonstrated that injury‐induced newborn neurons are required for hippocampus‐dependent spatial learning and memory tasks like the Morris water maze, but not in contextual fear conditioning that requires both the hippocampus and amygdala. Recently, the dentate gyrus, where adult hippocampal neurogenesis occurs, has been implicated in processing information to form specific memory under specific environmental stimuli in a process known as pattern separation. Methods To test whether injury‐induced newborn neurons facilitate pattern separation, hippocampus‐dependent contextual fear discrimination was performed using delta‐HSV‐TK transgenic mice, which can temporally inhibit injury‐induced neurogenesis under the control of ganciclovir. Results We observed that impaired neurogenesis enhanced the ability to distinguish aversive from naïve environments. In addition, this occurs most significantly following injury, but only in a context‐dependent manner whereby the sequence of introducing the naïve environment from the aversive one affected the performance differentially. Conclusions Temporal impairment of both baseline and injury‐induced adult neurogenesis enhances performance in fear discrimination in a context‐dependent manner. In this article, we employ our novel nestin‐HSV‐TK transgenic mouse developed and validated by us to inducibly ablate neurogenesis in the normal and injured settings. Interestingly, we see clear effects on fear discrimination, a dentate gyrus‐specific behavioral assay, but they are highly context dependent.