title: Electrolytic lesion of the nucleus incertus retards extinction of auditory conditioned fear.
abstract: Fear memory circuits in the brain function to allow animals and humans to recognize putative sources of danger and adopt an appropriate behavioral response; and research on animal models of fear have helped reveal the anatomical and neurochemical nature of these circuits. The nucleus (n.) incertus in the dorsal pontine tegmentum provides a strong GABAergic projection to forebrain 'fear centers' and is strongly activated by neurogenic stressors. In this study in adult male rats, we examined the effect of electrolytic lesions of n. incertus on different stages of the fear conditioning-extinction process and correlated the outcomes with anatomical data on the distribution of n. incertus-derived nerve fibers in areas implicated in fear circuits. In a contextual auditory fear conditioning paradigm, we compared freezing behavior in control (naïve) rats (n=23) and rats with sham- or electrolytic lesions of n. incertus (n=13/group). The effectiveness and extent of the lesions was assessed post-mortem using immunohistochemical markers for n. incertus neurons-calretinin and relaxin-3. There were no differences between the three experimental groups in the habituation, acquisition, or context conditioning phases; but n. incertus lesioned rats displayed a markedly slower, 'delayed' extinction of conditioned freezing responses compared to sham-lesion and control rats, but no differences in retrieval of extinguished fear. These and earlier findings suggest that n. incertus-related circuits normally promote extinction through inhibitory projections to the amygdala, which is involved in acquisition of extinction memories.
authors.affiliation: CIBERSAM, INCLIVA and Departamento de Anatomía y Embriología Humana, Facultad de Medicina, Universitat de Valencia, 46010 Valencia, Spain.
authors.forename: C W
authors.initials: CW
authors.lastname: Pereira
authors.forename: F N
authors.initials: FN
authors.lastname: Santos
authors.forename: A M
authors.initials: AM
authors.lastname: Sánchez-Pérez
authors.forename: M
authors.initials: M
authors.lastname: Otero-García
authors.forename: M
authors.initials: M
authors.lastname: Marchioro
authors.forename: S
authors.initials: S
authors.lastname: Ma
authors.forename: A L
authors.initials: AL
authors.lastname: Gundlach
authors.forename: F E
authors.initials: FE
authors.lastname: Olucha-Bordonau
mesh_terms: D000161:Acoustic Stimulation; D000679:Amygdala / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D064032:Calbindin 2; D003214:Conditioning, Classical / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology; D011149:Pons / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012065:Relaxin / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
chemical_list: C576764:CALB2 protein, human; C576512:Calb2 protein, rat; D064032:Calbindin 2; D009419:Nerve Tissue Proteins; C466742:RLN3 protein, rat; D064030:S100 Calcium Binding Protein G; D012065:Relaxin