Alcohol Dependence Modifies Brain Networks Activated During Withdrawal and Reaccess: A c-Fos-Based Analysis in Mice.

Background: High-level alcohol consumption causes neuroplastic changes in the brain that promote pathological drinking behavior. Some of these changes have been characterized in defined brain circuits and cell types, but unbiased approaches are needed to explore broader patterns of adaptations.

Methods: We used whole-brain c-Fos mapping and network analysis to assess patterns of neuronal activity during alcohol withdrawal and following reaccess in a well-characterized model of alcohol dependence.

Saracatinib Fails to Reduce Alcohol-Seeking and Consumption in Mice and Human Participants.

More effective treatments to reduce pathological alcohol drinking are needed. The glutamatergic system and the NMDA receptor (NMDAR), in particular, are implicated in behavioral and molecular consequences of chronic alcohol use, making the NMDAR a promising target for novel pharmacotherapeutics. Ethanol exposure upregulates Fyn, a protein tyrosine kinase that indirectly modulates NMDAR signaling by phosphorylating the NR2B subunit.

The effects of fatty acid amide hydrolase inhibition and monoacylglycerol lipase inhibition on habit formation in mice.

Emerging data indicate that endocannabinoid signaling is critical to the formation of habitual behavior. Previous work demonstrated that antagonism of cannabinoid receptor type 1 (CB1R) with AM251 during operant training impairs habit formation, but it is not known if this behavioral effect is specific to disrupted signaling of the endocannabinoid ligands anandamide or 2-arachidonoyl glycerol (2-AG). Here, we used selective pharmacological compounds during operant training to determine the impact of fatty acid amide hydrolase (FAAH) inhibition to increase anandamide (and other n-acylethanolamines) or monoacylglycerol lipase (MAGL) inhibition to increase 2-AG levels on the formation of habitual behaviors in mice using a food-reinforced contingency degradation procedure.

A Gut Feeling about Dopamine.

In this issue of Neuron, Fernandes et al. (2020) compare intra-gastric sugar and non-caloric sweetener to investigate how post-ingestive effects can be reinforcing, revealing a role for the hepatic vagus nerve in transforming sugar sensing by the gut into behavioral reinforcement via midbrain dopamine neuron responses.

Sex-Dependent Modulation of Anxiety and Fear by 5-HT Receptors in the Bed Nucleus of the Stria Terminalis.

Serotonin (5-hydroxytryptamine; 5-HT) coordinates behavioral responses to stress through a variety of presynaptic and postsynaptic receptors distributed across functionally diverse neuronal networks in the central nervous system. Efferent 5-HT projections from the dorsal raphe nucleus (DRN) to the bed nucleus of the stria terminalis (BNST) are generally thought to enhance anxiety and aversive learning by activating 5-HT receptor (5-HTR) signaling in the BNST, although an opposing role for postsynaptic 5-HT receptors has recently been suggested. In the present study, we sought to delineate a role for postsynaptic 5-HT receptors in the BNST in aversive behaviors using a conditional knockdown of the 5-HT receptor.

Endocannabinoid contributions to alcohol habits and motivation: Relevance to treatment.

Individuals with alcohol use disorder exhibit compulsive habitual behaviors that are thought to be, in part, a consequence of chronic and persistent use of alcohol. The endocannabinoid system plays a critical role in habit learning and in ethanol self-administration, but the role of this neuromodulatory system in the expression of habitual alcohol seeking is unknown. Here, we investigated the role of the endocannabinoid system in established alcohol habits using contingency degradation in male C57BL/6 mice.

Bi-directional modulation of food habit expression by the endocannabinoid system.

The compulsive, habitual behaviors that have been observed in individuals diagnosed with substance use disorders may be due to disruptions in the neural circuits that mediate goal-directed actions. The endocannabinoid system has been shown to play a critical role in habit learning, but the role of this neuromodulatory system in habit expression is unclear. Here, we investigated the role of the endocannabinoid system in established habitual actions using contingency degradation in male C57BL/6 mice.

Medial prefrontal D1 dopamine neurons control food intake.

Although the prefrontal cortex influences motivated behavior, its role in food intake remains unclear. Here, we demonstrate a role for D1-type dopamine receptor-expressing neurons in the medial prefrontal cortex (mPFC) in the regulation of feeding. Food intake increases activity in D1 neurons of the mPFC in mice, and optogenetic photostimulation of D1 neurons increases feeding.

The role of sleep in forming a memory representation of a two-dimensional space.

There is ample evidence from human and animal models that sleep contributes to the consolidation of newly learned information. The precise role of sleep for integrating information into interconnected memory representations is less well understood. Building on prior findings that following sleep (as compared to wakefulness) people are better able to draw inferences across learned associations in a simple hierarchy, we ask how sleep helps consolidate relationships in a more complex representational space.

From habits to self-regulation: how do we change?

The Yale Cognitive Science department hosted the conference "From Habits to Self-Regulation: How Do We Change?" on November 4 and 5, 2011, to showcase current research on self-control in cognitive science, psychology, and neuroscience. The conference included a panel discussion by four philosophers who gave context for the scope and limitations of research on self-control. The common theme concerning the best method to attain lasting change included becoming aware of what one wants to change, increasing commitment to the goal of change, and imagining all of the potential problems and solutions to those problems.

Hippocampal leptin signaling reduces food intake and modulates food-related memory processing.

The increase in obesity prevalence highlights the need for a more comprehensive understanding of the neural systems controlling food intake; one that extends beyond food intake driven by metabolic need and considers that driven by higher-order cognitive factors. The hippocampus, a brain structure involved in learning and memory function, has recently been linked with food intake control. Here we examine whether administration of the adiposity hormone leptin to the dorsal and ventral sub-regions of the hippocampus influences food intake and memory for food.