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Prefrontal NMDA receptors expressed in excitatory neurons control fear discrimination and fear extinction.
- Source :
-
Neurobiology of learning and memory [Neurobiol Learn Mem] 2015 Mar; Vol. 119, pp. 52-62. Date of Electronic Publication: 2015 Jan 20. - Publication Year :
- 2015
-
Abstract
- N-methyl-D-aspartate receptors (NMDARs) are critically involved in various learning mechanisms including modulation of fear memory, brain development and brain disorders. While NMDARs mediate opposite effects on medial prefrontal cortex (mPFC) interneurons and excitatory neurons, NMDAR antagonists trigger profound cortical activation. The objectives of the present study were to determine the involvement of NMDARs expressed specifically in excitatory neurons in mPFC-dependent adaptive behaviors, specifically fear discrimination and fear extinction. To achieve this, we tested mice with locally deleted Grin1 gene encoding the obligatory NR1 subunit of the NMDAR from prefrontal CamKIIα positive neurons for their ability to distinguish frequency modulated (FM) tones in fear discrimination test. We demonstrated that NMDAR-dependent signaling in the mPFC is critical for effective fear discrimination following initial generalization of conditioned fear. While mice with deficient NMDARs in prefrontal excitatory neurons maintain normal responses to a dangerous fear-conditioned stimulus, they exhibit abnormal generalization decrement. These studies provide evidence that NMDAR-dependent neural signaling in the mPFC is a component of a neural mechanism for disambiguating the meaning of fear signals and supports discriminative fear learning by retaining proper gating information, viz. both dangerous and harmless cues. We also found that selective deletion of NMDARs from excitatory neurons in the mPFC leads to a deficit in fear extinction of auditory conditioned stimuli. These studies suggest that prefrontal NMDARs expressed in excitatory neurons are involved in adaptive behavior.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Acoustic Stimulation
Animals
Auditory Perception physiology
Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism
Conditioning, Psychological physiology
Discrimination, Psychological physiology
Extinction, Psychological physiology
Female
Gene Knockout Techniques
Generalization, Response physiology
Male
Mice
Mice, Inbred C57BL
Nerve Tissue Proteins genetics
Neurons metabolism
Receptors, N-Methyl-D-Aspartate genetics
Fear physiology
Nerve Tissue Proteins physiology
Neurons physiology
Prefrontal Cortex physiology
Receptors, N-Methyl-D-Aspartate physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9564
- Volume :
- 119
- Database :
- MEDLINE
- Journal :
- Neurobiology of learning and memory
- Publication Type :
- Academic Journal
- Accession number :
- 25615540
- Full Text :
- https://doi.org/10.1016/j.nlm.2014.12.012