Activation of the habenula complex evokes autonomic physiological responses similar to those associated with emotional stress

Abstract

Neurons in the lateral habenula (LHb) discharge when an animal anticipates an aversive outcome or when an expected reward is not forthcoming, contributing to the behavioral response to aversive situations. So far, there is little information as to whether the LHb also contributes to autonomic physiological responses, including increases in body temperature (emotional hyperthermia) that are integrated with defensive behaviors. Vasoconstriction in cutaneous vascular bed and heat production in brown adipose tissue (BAT) both contribute to emotional hyperthermia. Our present study determines whether stimulation of the LHb elicits constriction of the tail artery and BAT thermogenesis in anesthetized Sprague-Dawley rats. Disinhibition of neurons in LHb with focal microinjections of bicuculline (1 nmol in 100 nl, bilaterally) acutely increased BAT temperature (+0.6 ± 0.1°C, n = 9 rats, P < 0.01) and reduced tail artery blood flow (by 88 ± 4%, n = 9 rats, P < 0.01). Falls in mesenteric blood flow, simultaneously recorded, were much less intense. The pattern of BAT thermogenesis and cutaneous vasoconstriction elicited by stimulating the habenula is similar to the pattern observed during stress-induced emotional hyperthermia, suggesting that the habenula may be important in this response.

Keywords: Body temperature; brown adipose tissue temperature; cutaneous blood flow; lateral habenula; thermoregulation.

Figure 1

Histological demonstration of bicuculline injection sites into LHb marked by ß-gal reaction products. CM, central medial thalamic nucleus; cpd, cerebral peduncle; f, fornix; LHb, lateral habenula; MD, mediodorsal thalamic nucleus; MHb, medial habenula; ml, medial lemniscus; mt mammillothalamic tract; LP, lateral posterior thalamic nucleus; opt, optic tract; Po, posterior thalamic nucleus; PVT, paraventricular thalamic nucleus; VPM, ventral posteromedial thalamic nucleus; 3V third ventricle.

Figure 2

Effect of bicuculline injection into LHb on tail and mesenteric blood flow, and their flow pulse amplitude, brown adipose tissue and body temperature (BAT temp, Body temp), arterial pressure, heart rate, end expiratory CO₂ (ExpCO₂), and respiratory rate under both nonparalysis. (A) Chart record from one anesthetized rat (B) Group data. Relative percentage difference from preinjection baseline level was shown in tail and mesenteric flow. Actual difference (Δ) from preinjection baseline level was shown in all other parameters.

Figure 3

Peri-stimulus averaged potentials of BAT sympathetic nerve evoked by electrical stimulation of LHb at time 0. Gray lines show 16 individual sweeps and black line shows an average of the 16 sweeps.