Paraventricular Thalamus Balances Danger and Reward

Abstract

Foraging animals balance the need to seek food and energy against the accompanying dangers of injury and predation. To do so, they rely on learning systems encoding reward and danger. Whereas much is known about these separate learning systems, little is known about how they interact to shape and guide behavior. Here we show a key role for the rat paraventricular nucleus of the thalamus (PVT), a nucleus of the dorsal midline thalamus, in this interaction. First, we show behavioral competition between reward and danger: the opportunity to seek food reward negatively modulates expression of species-typical defensive behavior. Then, using a chemogenetic approach expressing the inhibitory hM4Di designer receptor exclusively activated by a designer drug in PVT neurons, we show that the PVT is central to this behavioral competition. Chemogenetic PVT silencing biases behavior toward either defense or reward depending on the experimental conditions, but does not consistently favor expression of one over the other. This bias could not be attributed to changes in fear memory retrieval, learned safety, or memory interference. Rather, our results demonstrate that the PVT is essential for balancing conflicting behavioral tendencies toward danger and reward, enabling adaptive responding under this basic selection pressure.SIGNIFICANCE STATEMENT Among the most basic survival problems faced by animals is balancing the need to seek food and energy against the accompanying dangers of injury and predation. Although much is known about the brain mechanisms that underpin learning about reward and danger, little is known about how these interact to solve basic survival problems. Here we show competition between defensive (to avoid predatory detection) and approach (to obtain food) behavior. We show that the paraventricular thalamus, a nucleus of the dorsal midline thalamus, is integral to this behavioral competition. The paraventricular thalamus balances the competing behavioral demands of danger and reward, enabling adaptive responding under this selection pressure.

Keywords: competition; danger; paraventricular thalamus; reward.

Figure 1.

Competition between danger and reward. A, Design and procedure for None (n = 8) and Lever (n = 8) groups. B, Freezing behavior on the conditioning day for tone–shock pairings. C, Defense and reward behavior during tone presentations on the test day. Defense is percentage of observations where freezing was expressed. Reward is sum of approach behavior (lever press and food magazine entry). D, Scatterplot of freezing and reward behavior for Group Lever during tone presentations on test day. Data are means ± SEM. *p < 0.05.

Figure 2.

Effects of PVT silencing on competition between danger and reward. A, Design and procedure for Lever and Lever+ groups. B, Freezing behavior on the conditioning day for tone–shock pairings. C, Defense and reward behavior during tone presentations on the test day. Defense is percentage of observations where freezing was expressed. Reward is sum of approach behavior (lever press and food magazine entry). Data are means ± SEM. *p < 0.05. Group sizes were as follows: eYFP-Lever, n = 8; eYFP-Lever+, n = 7; hM4Di-Lever, n = 7; hM4Di-Lever+, n = 8.

Figure 3.

Effects of PVT silencing on danger in the absence and presence of reward. A, Design and procedure for the two stages. B, Freezing behavior on the conditioning day for tone–shock pairings and for tone presentations on test in Stage I. C, Freezing behavior on the conditioning day for each of the clicker–shock pairings in Stage II. D, Defense and reward behavior during clicker presentations on the test day. Defense is percentage of observations where freezing was expressed. Reward is sum of approach behavior (lever press and food magazine entry). Inset shows reward approach across blocks of two test trials. E, Comparison of freezing behavior during tone presentations on test in Stage I and Stage II. Data are means ± SEM. *p < 0.05. Group sizes were as follows: eYFP, n = 8; hM4Di, n = 8.

Figure 4.

Effects of PVT silencing on danger during hunger. A, Design and procedure for Hungry and Sated groups. B, Defense is freezing behavior on the conditioning day for the tone–shock pairings and on test. Data are means ± SEM. *p < 0.05. Group sizes were as follows: eYFP-Hungry, n = 8; eYFP-Sated, n = 8; hM4Di-Hungry, n = 8; hM4Di-Sated, n = 8.

Figure 5.

Effects of PVT silencing on instrumental responding for a food reward. A, Design and procedure. B, Behavior (sum of lever press and food magazine entry) on the final training day and CNO test day. Data are means ± SEM. Group sizes were as follows: eYFP, n = 8; hM4Di, n = 8.

Figure 6.

Effects of PVT silencing on discrimination between safe and dangerous memories. A, Design and procedure for renewal of extinguished fear. B, Freezing behavior on the conditioning day for each of the tone–shock pairings and on test, during extinction and on test. Data are means ± SEM. *p < 0.05. Group sizes were as follows: eYFP, n = 8; hM4Di, n = 8.

Figure 7.

A–E, Location of hM4Di expression for all rats in Experiments 2 (A), 3 (B), 4 (C) 5 (D), and 6 (E) with the maximal extent of DREADD expression represented at 10% opacity for each rat. F, Representative PVT section showing single-labeled c-fos (black arrow), single-labeled eYFP (white arrow), and dual-labeled eYFP/c-fos (blue arrow) neurons. Scale bar, 50 μm. G, Mean and SEM percentages of transduced neurons expressing c-fos for eYFP (n = 8), 15 mg/kg CNO-DREADD (n = 8), and 20 mg/kg CNO-DREADD (n = 8). *p < 0.05.