Journal
AMERICAN JOURNAL OF PSYCHIATRY
Volume 167, Issue 10, Pages 1178-1193Publisher
AMER PSYCHIATRIC PUBLISHING, INC
DOI: 10.1176/appi.ajp.2010.09081187
Keywords
-
Categories
Funding
- NARSAD
- NIMH [MH-076932, MH-080309, MH-062236, MH-083957]
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH080309, R01MH062236, R01MH076932, R01MH083957] Funding Source: NIH RePORTER
Ask authors/readers for more resources
The hippocampal formation is one of the most extensively studied regions of the brain, with well-described anatomy and basic physiology; moreover, aspects of human memory mediated by the hippocampus are well characterized. In schizophrenia, alterations in hippocampal anatomy, perfusion, and activation are consistently reported; impairments in declarative memory function, especially in the flexible use of event memories (e. g., in the service of memory-based inference), are common. Postmortem molecular changes suggest a selective reduction in glutamate transmission in the dentate gyrus and in its efferent fibers, the mossy fiber pathway. A reduction in dentate gyrus glutamatergic output and in its information processing functions could generate two co-occurring outcomes in the hippocampus: 1) a change in homeostatic plasticity processes in cornu ammonis 3 (CA3), accompanied by increased activity due to reduced afferent stimulation from the dentate gyrus onto CA3 neurons, a process that could increase the pattern completion functions of CA3, and 2) the loss of mnemonic functions specific to the dentate gyrus, namely pattern separation, a change that could increase the prevalence of illusory pattern completion and reduce discrimination between present and past experiences in memory. The resulting increase in runaway CA3-mediated pattern completion could result in cognitive mistakes, generating psychotic associations and resulting in memories with psychotic content. Tests of this model could result in novel approaches to the treatment of psychosis and declarative memory alterations and in novel animal preparations for basic schizophrenia research.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available