Premotor sympathetic neurons of conditioned fear in the rat

Abstract

Conditioned fear to context, a pure form of psychological stress, is associated with sympathetically mediated changes including a marked hypertension. To identify the possible premotor sympathetic neurons mediating these changes, we conducted double-immunolabelling experiments combining fear-induced Fos with retrograde tracing from the thoracic cord (T2-L1). Presympathetic groups showing the greatest increase in the proportion of spinally projecting cells double-labelled with Fos compared with resting controls were the perifornical area (PeF; 22.7% vs. 0.4%) and paraventricular nucleus (Pa; 10.5% vs. 0.2%) in the hypothalamus, and the A5 noradrenergic group (33.6% vs. 0.2%) in the pons. In contrast, there was only a small increase in the presympathetic groups of the rostral ventral medulla, including the lateral paragigantocellular group (LPGi; 4.3% vs. 0.5%), raphe magnus and pallidus (1.1% vs. 0.6% and 1.8% vs. 0.5%), and the vasopressor group of the rostral ventrolateral medulla (RVLM; 1.9% vs. 0.8%). PeF, Pa, A5 and LPGi accounted for 21, 15, 16 and 6% of all the double-labelled cells, respectively, and RVLM for only 1%. Double-immunolabelling of Fos and tyrosine hydroxylase confirmed that many A5 neurons were activated (19%) and that practically no C1 neurons in RVLM were (1.3%). The results suggest that the main premotor sympathetic drive of the fear response comes from hypothalamic (PeF and Pa) and A5 neurons that project directly to the thoracic cord and bypass medullary presympathetic groups, and that the vasopressor premotor sympathetic neurons of the RVLM are unlikely to mediate the hypertensive pressure response of contextual fear.