Hippocampal neurogenesis regulates recovery of defensive responses by recruiting threat-and extinction-signalling brain networks
Por:
Martinez-Canabal, Alonso, Lopez-Oropeza, Grecia, Gaona-Gamboa, Abril, Ballesteros-Zebadua, Paola, de la Cruz O.G., Moreno-Jimenez, Sergio, Sotres-Bayon, Francisco
Publicada:
27 feb 2019
Categoría:
Multidisciplinary
Resumen:
Safe exposure to a context that was previously associated with threat
leads to extinction of defensive responses. Such contextual fear
extinction involves the formation of a new memory that inhibits a
previously acquired contextual fear memory. However, fear-related
responses often return with the simple passage of time (spontaneous fear
recovery). Given that contextual fear and extinction memories are
hippocampus-dependent and hippocampal neurogenesis has been reported to
modify preexisting memories, we hypothesized that neurogenesis-mediated
modification of preexisting extinction memory would modify spontaneous
fear recovery. To test this, rats underwent contextual fear conditioning
followed by extinction. Subsequently, we exposed rats to an enriched
environment or focal X-irradiation to enhance or ablate hippocampal
neurogenesis, respectively. Over a month later, rats were tested to
evaluate spontaneous fear recovery. We found that enhancing neurogenesis
after, but not before, extinction prevented fear recovery. In contrast,
neurogenesis ablation after, but not before, extinction promoted fear
recovery. Using the neuronal activity marker c-Fos, we identified brain
regions recruited in these opposing neurogenesis-mediated changes during
fear recovery. Together, our findings indicate that neurogenesis
manipulation after extinction learning modifies fear recovery by
recruiting brain network activity that mediates the expression of
preexisting contextual fear and extinction memories.
Filiaciones:
Martinez-Canabal, Alonso:
Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Univ Nacl Autonoma Mexico, Inst Fisiol Celular Neurociencias, Mexico City 04510, DF, Mexico
Lopez-Oropeza, Grecia:
Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Univ Nacl Autonoma Mexico, Inst Fisiol Celular Neurociencias, Mexico City 04510, DF, Mexico
Gaona-Gamboa, Abril:
Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Univ Nacl Autonoma Mexico, Inst Fisiol Celular Neurociencias, Mexico City 04510, DF, Mexico
Ballesteros-Zebadua, Paola:
Instituto Nacional de Neurología y Neurocirugía – Radioneurocirugía, Ciudad de México, Mexico
Inst Nacl Neurol & Neurocirugia Radioneurocirugia, Mexico City, DF, Mexico
de la Cruz O.G.:
Instituto Nacional de Neurología y Neurocirugía – Radioneurocirugía, Ciudad de México, Mexico
Moreno-Jimenez, Sergio:
Instituto Nacional de Neurología y Neurocirugía – Radioneurocirugía, Ciudad de México, Mexico
Inst Nacl Neurol & Neurocirugia Radioneurocirugia, Mexico City, DF, Mexico
Sotres-Bayon, Francisco:
Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Univ Nacl Autonoma Mexico, Inst Fisiol Celular Neurociencias, Mexico City 04510, DF, Mexico
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