Biology subjects

van Mourik, Y.

Publications and source records attributed to van Mourik, Y..

4 recordsLinked to original sources

bioRxiv2026

Anterior insula activity during alcohol and social reward self-administration and choice in male and female rats

Alcohol use disorder (AUD) is characterized by the prioritization of alcohol over healthier non-alcohol rewards, posing significant challenges for addiction treatment. Understanding the neural mechanisms driving this maladaptive preference is crucial for effective intervention. We previously showed that rats will choose alcohol over social reward in a discrete-choice task. Here, we used fiber photometry to investigate how anterior insula cortex (aIC) activity relates to choice and employed Linear Ballistic Accumulator (LBA) modelling to dissect the underlying decision processes. Male and female rats, transfected with calcium indicator jGCaMP7f in aIC, were trained to lever-press for either social reward or alcohol (20% ethanol) in alternating sessions, followed by discrete-choice sessions, and then punishment of alcohol choices. Rats developed a preference for alcohol over social reward, which was reversed when alcohol choices were punished. Model output successfully described this behaviour with the model-derived decision bias tracking preference across all phases. Photometry recordings showed that, as alcohol preference emerged, increased aIC activity during the cue period preceding alcohol choices (relative to social choices) was significantly correlated with decision bias towards alcohol. During punishment, aIC activity bias was no longer related to decision bias, despite the preference shift. These results demonstrate that aIC activity is linked to alcohol reward and choice and suggest that aIC contributes to alcohol preference by encoding a bias in the evidence accumulation process. This highlights a specific role of aIC in the cognitive mechanisms of alcohol-seeking, and its potential as a target for therapeutic interventions. SignificanceUnderstanding the neural basis of prioritizing alcohol over natural rewards is critical for combating alcohol use disorder. This study investigates how anterior insula cortex (aIC) activity in rats relates to choices between alcohol and social reward. Using fiber photometry and cognitive modelling, we found that aIC activity is not only consistently higher for alcohol-related actions but also, during the decision period prior to choice. Differential activity for alcohol versus social choices significantly correlates with a model-derived "decision bias", the speed of evidence accumulation, favouring alcohol, once preference is established. This provides novel mechanistic insight, suggesting aIC contributes to alcohol preference by encoding a bias in the decision-making process, highlighting its role in alcohol seeking and as a potential therapeutic target.

neuroscience↗

bioRxiv2025

Dual Role of LH-GABA Neurons in Encoding Alcohol Reward and Aversive Memories

One of the core aspects of alcohol use disorder is continued use despite negative consequences. Individuals with an alcohol use disorder typically engage in behaviors which represent a failure to integrate the aversive consequences of their actions. The neural mechanisms of learning about conflicting experiences remain poorly understood. Previous research has highlighted the critical role of GABAergic neurons in the Lateral Hypothalamus (LH-GABA) in rewarding memories. However, whether this role extends to aversive outcomes, and competition between rewarding and aversive outcomes remains unexplored. In this study, we sought to elucidate the role of LH-GABA neurons in encoding and expressing alcohol reward and aversive memories using fiber photometry calcium imaging. We used a dual-virus approach to confine expression of jGCaMP7f to GABAergic neurons in LH of male and female Long-Evans rats. In our first experiment, following acquisition of a cue-alcohol association, a mild foot shock was introduced on 50% of the trials. In the second experiment, we used three different cues to signal alcohol, foot-shock, or no consequence. Subsequently, we combined these conditioned stimuli in pairs to evoke motivational conflict. Our results reveal that LH-GABA activity is associated with cues predictive of both appetitive and aversive outcomes and is highest to a cue predictive of an aversive outcome. Additionally, the response of LH-GABA activity to an aversive shock stimulus is attenuated in the presence of alcohol. In summary, our findings show the activity of LH-GABA neurons is involved in learning both appetitive and aversive associations, and their interaction in conflict. Significance statement.This study addresses a critical knowledge gap in understanding the neural mechanisms behind learning in conflicting situations. Focusing on the GABAergic neurons in Lateral Hypothalamus, which have previously been associated with rewarding memories and motivation, we explore their role in the competition between rewarding and aversive motivation. We used fiber photometry to record LH-GABA neurons and found that their activity is heightened for aversive outcomes, irrespective of certainty. Notably, in situations of motivational conflict, this activity to the shock is dampened in the presence of alcohol. These insights not only enhance our understanding of the neural basis of emotional adaptation but also hold implications for psychiatric disorders like alcohol use disorder, depression, and anxiety, providing potential avenues for therapeutic interventions.

neuroscience↗

bioRxiv2019

From stress to depression: Development of extracellular matrix-dependent cognitive impairment following social stress

Stress can predispose to depressive episodes, yet the molecular mechanisms regulating the transition from the initial stress response to a persistent pathological depressive state remain poorly understood. To shed light on this stress-to-depression transition process, we profiled the development of an enduring depressive-like state in rat by assessing affective behavior and hippocampal function during the 2 months following social defeat stress. In addition, we measured remodeling of hippocampal extracellular matrix (ECM) during this period, as we recently identified ECM changes to mediate cognitive impairment during a sustained depressive-like state. We found affective disturbance and cognitive impairment to develop disparately after social stress. While affective deficits emerged gradually, spatial memory impairment was present both early after stress and during the late-emerging chronic depressive-like state. Surprisingly, these phases were separated by a period of normalized hippocampal function. Similarly, the SDPS paradigm induced a biphasic regulation of the hippocampal ECM coinciding with hippocampus-dependent memory deficits. Early after stress, synaptic ECM proteins and the number of perineuronal nets enwrapping parvalbumin-expressing interneurons were decreased. This was followed by a recovery period without ECM dysregulation, before subsequent decreased metalloproteinase activity and ECM build-up, previously shown to impair memory. This suggests that intact hippocampal function requires unaltered ECM levels. Together our data 1) reveal a dichotomy between affective and cognitive impairments similar to that observed in patients, 2) indicate different molecular processes taking place during early stress and the chronic depressive-like state, and 3) support a role of the ECM in mediating long-lasting memory-effects of social stress.

neuroscience↗

bioRxiv2018

Stress vulnerability promotes an alcohol prone phenotype in a preclinical model of sustained depression

Major depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat-induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (5 episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction and cue-induced reinstatement of alcohol-seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, excessive motivation to acquire alcohol, persistent alcohol-seeking despite alcohol unavailability, extinction resistance and increased cue-induced relapse; the latter could be blocked by the 2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol-seeking and -taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.

animal behavior and cognition↗