The medial hypothalamic defensive circuit and 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) induced fear: Comparison of electrolytic and neurotoxic lesions

The neural circuits for unconditioned fear to predator odors (e.g., cat fur odor, trimethylthiazoline, TMT) are not well delineated. A putative neural circuit for predator odor fear, the medial hypothalamic defensive circuit (MHDC), consisting of the anterior hypothalamic (AHN), ventromedial hypothalamic (VMH) and dorsal premammillary nuclei (PMd), has been proposed. Electrolytic and ibotenic acid lesions of the PMd have been shown to reduce unconditioned fear in rats presented with either a cat or cat odor. Whether the PMd, AHN and VMH are involved in unconditioned fear to another predator odor derived from fox feces, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), has not been explored. The present study compared the effects of electrolytic and neurotoxic lesions of MHDC nuclei in rats on unconditioned fear to TMT and shock-induced contextually conditioned fear, as measured by freezing. Electrolytic lesions of the PMd did not reduce TMT-induced freezing, but diminished post-shock and shock-induced contextually conditioned freezing, suggesting a role for the PMd in contextually conditioned fear. In contrast, electrolytic lesions of the AHN and VMH reduced freezing to TMT while not affecting conditioned fear. However, neither NMDA lesions of the AHN nor ibotenic acid lesions of the VMH reduced freezing in shock-induced conditioned or TMT-induced unconditioned fear paradigms. The data suggest that fibers passing through the AHN and VMH, and not cells in the MHDC, mediate unconditioned freezing to the predator odor TMT.