Four experiments tested whether an odor from a rat predator can unconditionally elicit a fear response in rats. In a large chamber, rats displayed fear-related behaviors to trimethylthiazoline (TMT, a volatile compound isolated from fox feces), including avoidance and immobility, while showing less exploratory behavior. In a smaller chamber, TMT induced a species-typical fear response, freezing, whereas other odors did not. In addition, TMT systematically elicited more freezing as the amount of TMT increased. Moreover, there was no within-sessions or between-sessions habituation of freezing to TMT, nor did TMT promote contextual conditioning. The results indicate that the predator odor, TMT, can induce a fear-related behavioral response in rats that is controllable and quantifiable, suggesting that TMT-induced freezing may be a useful paradigm for a neurobehavioral system analysis of ecologically relevant, unconditioned fear.

Considerable evidence suggests that the lateral (LA) and basal (BA) nuclei of the amygdala are sites of plasticity and storage of emotional memory. Recent arguments, however, have seriously challenged this view, suggesting that the effects of amygdala lesions are attributable to interference with performance of fear behavior and not learning and memory. One way to address this controversy is to measure the same behavioral response during both conditioned and unconditioned fear. This is done in the present study by measuring fear-related freezing behavior after electrolytic and neurotoxic lesions of the LA or LA/BA nuclei in rats in a contextual fear conditioning paradigm and unconditioned fear to a predator odor. Electrolytic LA lesions attenuated post-shock freezing, retention test freezing, and freezing to the predator odor trimethylthiazoline (TMT). In contrast, excitotoxic NMDA lesions of the LA had no effect on post-shock freezing but significantly attenuated retention test freezing. Furthermore, excitotoxic LA lesions did not diminish freezing to TMT. Larger excitotoxic lesions that included the BA significantly reduced freezing in both the post-shock and retention tests but did not appreciably decrease freezing to TMT. The results suggest that the LA is important for memory of learned fear but not for generation of freezing behavior. In addition, the BA plays a role in freezing in conditioned fear situations but not in unconditioned fear. The studies suggest that the LA and BA play different roles in fear conditioning, but neither of them has a significant role in unconditioned freezing to a predator odor.

Studies of gene expression following fear conditioning have demonstrated that the inducible transcription factor, egr-1, is increased in the lateral nucleus of the amygdala shortly following fear conditioning. These studies suggest that egr-1 and its protein product Egr-1 in the amygdala are important for learning and memory of fear. To directly test this hypothesis, an egr-1 antisense oligodeoxynucleotide (antisense-ODN) was injected bilaterally into the amygdala prior to contextual fear conditioning. The antisense-ODN reduced Egr-1 protein in the amygdala and interfered with fear conditioning. A 250-pmole dose produced an 11% decrease in Egr-1 protein and reduced long-term memory of fear as measured by freezing in a retention test 24 h after conditioning, but left shock-induced freezing intact. A larger 500-pmole dose produced a 25% reduction in Egr-1 protein and significantly decreased both freezing immediately following conditioning and freezing in the retention test. A nonsense-ODN had no effect on postshock or retention test freezing. In addition, 500 pmole of antisense-ODN infused prior to the retention test in previously trained rats did not reduce freezing, indicating that antisense-ODN did not suppress conditioned fear behavior. Finally, rats infused with 500 pmole of antisense-ODN displayed unconditioned fear to a predator odor, demonstrating that unconditioned freezing was unaffected by the antisense-ODN. The data indicate that the egr-1 antisense-ODN interferes with learning and memory processes of fear without affecting freezing behavior and suggests that the inducible transcription factor Egr-1 within the amygdala plays important functions in long-term learning and memory of fear.

Sir-Authorship is the currency of modern science, the measure of one's contribution to the literature. Yet while the contents of an article are held to strict scientific standards, the recognition of authorship is far less so. With no accepted system to guide the process by which authors are recognized for their individual contributions, and with the numbers of authors per article steadily increasing, the incidence of authorship disputes and abuse is rising, as Eugen Tarnow noted in Correspondence ("When extra authors get in on the act" Nature 398, 657; 1999). Certain medical journals now require authorship declarations, although these are always qualitative. We suggest a quantitative method for evaluating authorship based on four categories of contribution: conception and design, data collection, data analysis and conclusions, and manuscript preparation. Each author would claim their percentage share of the total credit in each of the four categories. The least that one could contribute to a paper would be 10% within a single category, placing a theoretical limit of 40 on the total number of authors. Authors would usually be listed in descending order of total contribution correspondence