Auditory cognitive training improves prepulse inhibition in serine racemase mutant mice

AbstractEvidence indicates that neuroplasticity-based cognitive training can improve cognition in patients with schizophrenia, but the individual response to training varies greatly between subjects. Hence, there is a need to understand the neurological underpinnings of cognitive training to reveal predictors of treatment response.d-serine is a crucial modulator of neuroplasticity, and decreased levels ofd-serine may contribute to deficits in neuroplasticity in schizophrenia. Interestingly, we observed that training mice to identify auditory oddballs increased extracellular levels ofd-serine in the hippocampus during training. Serine racemase (Srr) is the only source of braind-serine; thus, it is possible that Srr may mediate the response to training. To test this hypothesis, we trained mice that have a mutated version of Srr (SrrY269*/SrrY269*) and reduced levels ofd-serine in the same auditory training. SrrY269*/SrrY269* mice showed decreased performance during auditory training (defined as the capacity to discriminate an oddball during a sequence of tones). Importantly, auditory training improved prepulse inhibition (PPI) in SrrY269*/SrrY269* but not in wild-type mice. Finally,d-serine (100 mg/kg i.p.) given 30 min before training sessions to SrrY269*/SrrY269* mice improved training performance, but it did not enhance PPI. Taken together, our results show thatd-serine is involved in the response to neuroplasticity-based auditory training and that PPI deficits can be improv...

Source: Psychopharmacology - July 10, 2020 Category: Psychiatry Source Type: research