Wired to eat

This dissertation investigates the neural mechanisms underlying stress and food reward, with a particular focus on how these processes interact. An important brain region linking these domains is the ventral tegmental area (VTA), a midbrain region historically associated with reward and motivation. Stress and food reward are two major modulators of motivated behavior. Stress can increase the consumption of palatable food following stressful experiences, a phenomenon known as stress eating. This dissertation examines the neural mechanisms underlying stress eating. In Chapter 2, we show that stress strengthens glutamatergic synapses from the lateral hypothalamic area (LHA) onto dopamine neurons in the ventral tegmental area (VTADA). This strengthening is causally related to increased consumption of calorie-dense food after stress. Stress increases dopamine release in the prefrontal cortex, but not in the medial shell of the nucleus accumbens. In Chapter 3, we investigate how stress affects endocannabinoid-mediated short-term plasticity. We find that stress reduces depolarization-induced suppression of inhibition (DSI) at GABAergic synapses from the LHA onto VTADA neurons, while inducing depolarization-induced suppression of excitation (DSE) at glutamatergic synapses. This suggests that stress decreases the likelihood of VTADA neuron activation following stress. In Chapter 4, we characterize VTA neurons that are activated by acute social stress. These stress-sensitive neurons show increased excitability compared to neighboring neurons that are not stress-responsive. In Chapter 5, we investigate the functional connectivity between different striatal regions. We find that stimulation of the ventromedial striatum (VMS) and the dorsolateral striatum (DLS) causes dopamine release in the posterior dorsomedial striatum (pDMS). This is likely mediated by disinhibition of dopamine neurons via GABAergic neurons in the substantia nigra. Chapter 6 is a review in which we discuss current methodologies and practical considerations when using optogenetics and patch-clamp electrophysiology. The combination of these techniques has proven to be an indispensable tool in neuroscience. This dissertation provides insight into the neural circuits involved in stress and food reward, with a focus on stress eating. The findings suggest that stress induces specific synaptic changes that increase the consumption of calorie-dense food following stress. My experiences inside and outside the laboratory with brains, stress, and eating have convinced me of the need for a food system that promotes healthy choices. It is important that our society provides structural support to make healthier choices easier.