The cognitive (lateral) hypothalamus

Abstract

Despite the physiological complexity of the hypothalamus, its role is typically restricted to initiation or cessation of innate behaviors. For example, theories of lateral hypothalamus argue that it is a switch to turn feeding 'on' and 'off' as dictated by higher-order structures that render when feeding is appropriate. However, recent data demonstrate that the lateral hypothalamus is critical for learning about food-related cues. Furthermore, the lateral hypothalamus opposes learning about information that is neutral or distal to food. This reveals the lateral hypothalamus as a unique arbitrator of learning capable of shifting behavior toward or away from important events. This has relevance for disorders characterized by changes in this balance, including addiction and schizophrenia. Generally, this suggests that hypothalamic function is more complex than increasing or decreasing innate behaviors.

Keywords: addiction; feeding; lateral hypothalamus; reinforcement learning; reward; schizophrenia.

Figure 1.. Lateral hypothalamus mediates a balance in learning to relevant and irrelevant information.

The complexity of our environment means that we need to select information that we attend, learn, and direct behavior towards. In a healthy individual, this involves devoting most cognitive resources towards reward cues (green) and less to other cues that are not currently reward relevant (blue), which may or may not become important later on (left panel: “optimal bias to rewards”). A critical dissociation seen when manipulating lateral hypothalamic activity suggests that this region is critical to mediating this balance. Specifically, optical inhibition of lateral hypothalamus reduces learning about cues predicting food [32]. However, the same inhibition of lateral hypothalamus enhances learning about neutral cues, or cues that are distal predictors of food. This demonstrates that the lateral hypothalamus biases cognitive resources towards cues proximal to rewards, and away from distal predictors [32]. We propose that lateral hypothalamus could act as a dial that can increase or decrease the discrepancy in encoding reward-relevant and irrelevant information. Specifically, less activity in the lateral hypothalamus could reduce the difference in cognitive resources devoted to reward or neutral cues (e.g., the pattern seen in schizophrenia [81]; middle panel: “no bias to rewards”), while more activity in lateral hypothalamus could enhance cognitive resources devoted to rewards in a maladaptive way (e.g., as seen in addiction; right panel: “overbias to rewards”).

Figure I.. Dissociating learning and performance.

Typically, we examine the impact of circuit inhibition on a behavior when the animal is actively learning about reward-related information (learning; left). In order to determine whether this is an effect on learning and not performance, we need to conduct an extinction test in the absence of the reward and without circuit inhibition. This will reveal the long-term consequences of circuit inhibition and whether there is a meaningful influence on acquisition of the reward memory.

Figure I.. A dynamic dopamine system that balances many forms of learning.

We propose that lateral hypothalamus acts within a specific dopamine microcircuit to bias learning towards rewards, and away from neutral or distal cues. This constitutes one circuit acting to achieve a learning agenda, which is complemented by many other circuits that act to achieve bias learning consistent with other agendas (e.g., orbitofrontal cortex [74, 77, 109], amygdala [110], and prelimbic cortex [56]). Shifts away from optimal balance could contribute to psychological disorders, like addiction and schizophrenia.