Induction of fear extinction with hippocampal-infralimbic BDNF.
Enviado por Loyda Milagros Melendez, Ph.D. el
Título | Induction of fear extinction with hippocampal-infralimbic BDNF. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Autores | Peters, J, Dieppa-Perea, LM, Melendez, LM, Quirk, GJ |
Journal | Science |
Volume | 328 |
Issue | 5983 |
Pagination | 1288-90 |
Date Published | 2010 Jun 4 |
ISSN | 1095-9203 |
Palabras clave | Animals, Brain-Derived Neurotrophic Factor, Conditioning (Psychology), Excitatory Amino Acid Antagonists, Extinction, Psychological, Fear, Hippocampus, Humans, Male, Memory, Neural Pathways, Piperazines, Prefrontal Cortex, Rats, Rats, Sprague-Dawley, Receptors, N-Methyl-D-Aspartate, Recombinant Proteins |
Abstract | The extinction of conditioned fear memories requires plasticity in the infralimbic medial prefrontal cortex (IL mPFC), but little is known about the molecular mechanisms involved. Brain-derived neurotrophic factor (BDNF) is a key mediator of synaptic plasticity in multiple brain areas. In rats subjected to auditory fear conditioning, BDNF infused into the IL mPFC reduced conditioned fear for up to 48 hours, even in the absence of extinction training, which suggests that BDNF substituted for extinction. Similar to extinction, BDNF-induced reduction in fear required N-methyl-D-aspartate receptors and did not erase the original fear memory. Rats failing to learn extinction showed reduced BDNF in hippocampal inputs to the IL mPFC, and augmenting BDNF in this pathway prevented extinction failure. Hence, boosting BDNF activity in hippocampal-infralimbic circuits may ameliorate disorders of learned fear. |
DOI | 10.1126/science.1186909 |
Alternate Journal | Science |
PubMed ID | 20522777 |
PubMed Central ID | PMC3570764 |
Grant List | G12 RR003051-20 / RR / NCRR NIH HHS / United States MH058883 / MH / NIMH NIH HHS / United States MH081975 / MH / NIMH NIH HHS / United States MH083516 / MH / NIMH NIH HHS / United States MH085383 / MH / NIMH NIH HHS / United States NS043011 / NS / NINDS NIH HHS / United States RR003051 / RR / NCRR NIH HHS / United States |