Selective neuronal degeneration in the retrosplenial cortex impairs the recall of contextual fear memory

ERIC L. SIGWALD; MANUEL E. GENOUD; MARCELO GIACHERO; SOLEDAD DE OLMOS ; VıCTOR A. MOLINA; ALFREDO LORENZO

BRAIN STRUCTURE & FUNCTION

SPRINGER HEIDELBERG

Lugar: HEIDELBERG; Año: 2016

1863-2653

The retrosplenial cortex (RSC) is one of thelargest cortical areas in rodents, and is subdivided in twomain regions, A29 and A30, according to their cytoarchitecturalorganization and connectivities. However, verylittle is known about the functional activity of each RSCsubdivision during the execution of complex cognitivetasks. Here, we used a well-established fear learning protocolthat induced long-lasting contextual fear memory andshowed that during evocation of the fear memory, the expressionof early growth response gene 1 was up-regulatedin A30, and in other brain areas implicated in fear andspatial memory, however, was down-regulated in A29,including layers IV and V. To search for the participationof A29 on fear memory, we triggered selective degenerationof neurons within cortical layers IV and V of A29by using a non-invasive protocol that takes advantage ofthe vulnerability that these neurons have MK801-toxicityand the modulation of this neurodegeneration by testosterone.Application of 5 mg/kg MK801 in intact malesinduced negligible neuronal degeneration of A29 neuronsand had no impact on fear memory retrieval. However, inorchiectomized rats, 5 mg/kg MK801 induced overt degenerationof layers IV?V neurons of A29, significantlyimpairing fear memory recall. Degeneration of A29 neuronsdid not affect exploratory or anxiety-related behaviornor altered unconditioned freezing. Importantly, protectingA29 neurons from MK801-toxicity by testosterone preservedfear memory recall in orchiectomized rats. Thus,neurons within cortical layers IV?V of A29 are criticallyrequired for efficient retrieval of contextual fear memory.