A Novel Role for the Periaqueductal Gray in Consummatory Behavior

The periaqueductal gray (PAG) has a well-established role in pain processing, autonomic function and behavioral responses to fear. Anatomical work suggests the PAG may mediate food intake and reward processing as it has extensive reciprocal connections within brain circuits that mediate appetitive processes and consummatory behaviors such as prefrontal cortex, hypothalamus, amygdala, parabrachial nucleus (PBN) and ventral tegmental area (Kelley et al., 2005). Therefore, we investigated if the PAG of hungry rats has a functional role in appetitive and consummatory behaviors. To address this, PAG was pharmacologically inactivated during a spatial working memory task with muscimol (0.1–0.3 μg), a GABAA agonist via intracranial infusion. Inactivation of PAG led to reduced intake of food rewards and increased errors on this task. To focus on the specific effects PAG inactivation had on food consumption, PAG was inactivated during two separate food intake tasks in a separate group of rats. Again, PAG inactivation resulted in a significant decrease in food consumption, as well as an increased latency to consume food. We next investigated PAG neural responses to reward encounters. A different group of rats performed the same task used in Experiment 1 while the in vivo activity of PAG neurons was recorded. In a subset of PAG neurons, reward encounters elicited phasic excitation. A separate subset of PAG neurons were inhibited during reward encounters. These responses scaled with the size of the reward, with sustained excitation or inhibition in response to large rewards compared to small. Our data also show that separate groups of PAG neurons in awake behaving animals display either increased and decreased neural responses to reward encounters. Additionally, a proportion of neurons were modulated by the animals’ velocity. This study is the first to show that PAG neurons process reward-related information, perhaps to mediate consummatory behaviors related to food consumption

The Lateral Habenula Circuitry: Reward Processing and Cognitive Control

There has been a growing interest in understanding the role of the lateral habenula (LHb) in reward processing, affect regulation, and goal-directed behaviors. The LHb gets major inputs from the habenula-projecting globus pallidus and the mPFC, sending its efferents to the dopaminergic VTA and SNc, serotonergic dorsal raphe nuclei, and the GABAergic rostromedial tegmental nucleus. Recent studies have made advances in our understanding of the LHb circuit organization, yet the precise mechanisms of its involvement in complex behaviors are largely unknown. To begin to address this unresolved question, we present here emerging cross-species perspectives with a goal to provide a more refined understanding of the role of the LHb circuits in reward and cognition. We begin by highlighting recent findings from rodent experiments using optogenetics, electrophysiology, molecular, pharmacology, and tracing techniques that reveal diverse neural phenotypes in the LHb circuits that may underlie previously undescribed behavioral functions. We then discuss results from electrophysiological studies in macaques that suggest that the LHb cooperates with the anterior cingulate cortex to monitor action outcomes and signal behavioral adjustment. Finally, we provide an integrated summary of cross-species findings and discuss how further research on the connectivity, neural signaling, and physiology of the LHb circuits can deepen our understanding of the role of the LHb in normal and maladaptive behaviors associated with mental illnesses and drug abuse

Lubiprostone Stimulates Duodenal Bicarbonate Secretion in Rats

Lubiprostone, a bicyclic fatty acid, is used for the treatment of chronic constipation. No published study has addressed the effect of lubiprostone on intestinal ion secretion in vivo. The aim of this study was to test the hypothesis that lubiprostone augments duodenal HCO3 − secretion (DBS). Rat proximal duodenal loops were perfused with pH 7.0 Krebs, control vehicle (medium-chain triglycerides), or lubiprostone (0.1–10 μM). We measured DBS with flow-through pH and CO2 electrodes, perfusate [Cl−] with a Cl− electrode, and water flux using a non-absorbable ferrocyanide marker. Some rats were pretreated with a potent, selective CFTR antagonist, CFTRinh-172 (1 mg/kg, ip), 1 h before experiments. Perfusion of lubiprostone concentration dependently increased DBS, whereas net Cl− output and net water output were only increased at 0.1 μM, compared with vehicle. CFTRinh-172 reduced lubiprostone (10 μM)-induced DBS increase, whereas net Cl− output was also unchanged. Nevertheless, CFTRinh-172 reduced basal net water output, which was reversed by lubiprostone. Furthermore, lubiprostone-induced DBS was inhibited by EP4 receptor antagonist, not by an EP1/2 receptor antagonist or by indomethacin pretreatment. In this first study of the effect of lubiprostone on intestinal ion secretion in vivo, lubiprostone stimulated CFTR-dependent DBS without changing net Cl− secretion. This effect supports the hypothesis that Cl− secreted by CFTR is recycled across the apical membrane by anion exchangers. Recovery of water output during CFTR inhibition suggests that lubiprostone may improve the intestinal phenotype in CF patients. Furthermore, increased DBS suggests that lubiprostone may protect the duodenum from acid-induced injury via EP4 receptor activation