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25.04.2026, Saturday, 15:15-17:00
Understanding how the brain links events that were never directly paired is central to explaining complex learning, daily choices, belief formation, and the emergence of maladaptive perceptions. Higher-order conditioning, including sensory preconditioning, provides a powerful framework to investigate how neutral cues become meaningfully associated through incidental experience. This symposium brings together leading and emerging researchers who use cutting-edge behavioral models, computational approaches, and neurobiological techniques to uncover how such indirect associations shape cognition and how their dysregulation may contribute to psychotic-like states.
Dr. Arnau Busquets-Garcia(Hospital del Mar Research Institute, Barcelona) will open the session by presenting innovative paradigms that assess higher-order learning across multiple sensory modalities and social contexts. Expanding on the mechanistic level, Melie Talaron(University of Bordeaux & University of Sydney) will demonstrate how the hippocampus supports sensory preconditioning in rodents. Using refined behavioral assays combined with circuit-specific approaches, she will illustrate how hippocampal computations integrate neutral cue relationships and prepare downstream regions for later value assignment. Next, Unai Blanco(Neurocentre Magendie, Bordeaux) will discuss how incidental associations are encoded at the neural level. Drawing on in vivo imaging and targeted manipulations, he will reveal how distributed circuits capture relationships between seemingly irrelevant stimuli, offering insight into how associative maps are built spontaneously during experience.
The symposium will turn toward translational relevance. Irene García Manzanareswill present compelling findings showing that sensory preconditioning can serve as a sensitive behavioral window into cannabis-induced psychotic-like phenomena. Her data reveal how cannabinoids distort higher-order learning processes, providing a mechanistic bridge between incidental associations and vulnerability to psychotic symptoms. Finally, Dr. Natalia Zernicka-Glover(Francis Crick Institute, London) will share new results linking hallucination-like perception to neuromodulatory states and sleep. Her work highlights how altered internal models and disrupted inference may arise from aberrant associative processing, with direct implications for understanding the biological roots of hallucinations.
Together, these talks offer a coherent and multidisciplinary view of higher-order conditioning from basic mechanisms to their pathological consequences. By integrating behavioral neuroscience, circuit analysis, and models of psychosis, this symposium will stimulate discussion across fields and showcase how studying incidental associations can illuminate both normal cognition and the origins of disordered perception.
Hospital del Mar Research Institute (Barcelona, Spain)
"Behavioral Paradigms that Assess Higher-Order Learning Across Multiple Sensory Modalities"
Animals and humans adapt to changes in the environment through the encoding and storage of previous experiences. Although associative learning involving a reinforcer has been the major focus in the field of cognition, other forms of learning are gaining popularity as they are likely more relevant and frequent in human daily choices. Indeed, associations between non-reinforcing stimuli represent the most evolutionarily advanced way to increase the chances of predicting future events and adapting individuals’ behavior. Animals are also able to form these higher-order conditioning processes, but more research is needed to understand how the brain encode and store these complex cognitive processes. Arnau, a senior researcher that hold an ERC Starting Grant on this topic, will show different examples of higher-order conditioning paradigms in mice and how his lab is investigating the brain circuits involved.
Université de Bordeaux (France) & University of Sidney (Australia)
"Investigating the Role of the Hippocampus in Sensory Preconditioning"
Animals and people integrate information acquired at different times to respond appropriately in novel situations. Sensory preconditioning (SPC) in rats models this integration and allows to study its neural substrates. However, the precise role of the hippocampus in SPC remains unclear due to inconsistent protocols across studies. The research of Melie Talaron, PhD student between Bordeaux and Sydney universities, uses an auditory-visual SPC protocol in rats to reveal stage-specific hippocampal contributions: the dorsal hippocampus (dHPC) is critical during memory integration and subsequent retrieval, but is dispensable during initial stimulus learning. The ventral hippocampus shows distinct involvement patterns. Through pharmacological methods, we also demonstrate that the dHPC supports memory integration via NMDA receptor-dependent plasticity. The research additionally identifies distinct activity patterns across the perirhinal cortex-hippocampus-basolateral amygdala network during integration. These findings advance understanding of how the brain constructs flexible behavioral responses from temporally separated experiences, with implications for psychiatric disorders.
Neurocentre Magendie, Bordeaux, France
"The Role of the Endocannabinoid System in Incidental Associations: Focus on Interactions with Dopamine Signaling"
Many daily behaviors rely on unreinforced connections between low-salience stimuli known as Incidental Associations (IAs). To study them in rodents, sensory preconditioning tasks are used, where two low salience stimuli (S1/S2) are presented together during preconditioning, followed by conditioning of S1 with a reinforcer. As a result, subjects present direct responses to the S1 stimulus but also mediated responses to the S2 stimulus never explicitly reinforced, indicating IA formation. The endocannabinoid (eCB) system, particularly CB1 receptors (CB1R), is essential: hippocampal CB1R knockouts lacked mediated responses despite intact direct learning. Dopaminergic system also contributes, as mice lacking CB1R in D1-receptor- expressing cells failed to form IAs. Additionally, enhancing CB1R signaling with THC or boosting endogenous cannabinoids (JZL195) facilitated IA formation under conditions that are insufficient for controls. This effect of THC was also observed in D1R-CB1-KO, however, this effect was abolished when JZL195 was administered, meaning that D1R-CB1R positive cells are essential for physiological but not pharmacologically induced IAs.
Francis Crick Institute & UCL – Division of Psychiatry, London, UK
"The Impact of Sleep Deprivation on Psychosis-Like Perception in Mice"
Lack of sleep can profoundly disrupt perception, from disturbing our sense of time to triggering psychosis-like states. This project investigates how sleep deprivation alters perceptual experience, focusing on striatal neuromodulatory signalling. In mice, acute sleep loss significantly changes psychosis-like behaviours, including disrupted sensorimotor gating and hyperlocomotion. To observe perception directly, we use the HALIP (hallucination-like perception) task, in which mice report the presence of a tone embedded in a noisy background and express decision confidence by waiting for a reward. Sleep-deprived mice show increased hallucination-like percepts-high-confidence false alarms- indicating sleep loss alters not only psychosis-like behaviours but induces perceptual changes characteristic of psychosis. To uncover the mechanisms driving these changes, we are integrating behavioural results with in-vivo dopamine and serotonin fluorescence measurements, alongside broad metabolomic profiling of the brain and cerebrospinal fluid. Ultimately, this work aims to reveal the neural underpinnings of how sleep deprivation shapes psychosis-like perception.
Hospital del Mar Research Institute, Barcelona, Spain
"New Behavioral Approaches to Study Positive Psychotic-Like States Driven by Delta-9-Tetrahydrocannabinol in Mice"
The neurobiology underlying cannabis-induced positive psychotic-like states remains poorly understood, partly due to the lack of more precise animal behavioural models. Recently, higher-order conditioning has been proposed to model positive psychotic-like behavioral alterations. In rodents, this can be studied through sensory preconditioning tasks where associations between neutral stimuli can later evoke conditioned responses through mediated learning (ML). Increasing these associations in a preconditioning phase, ML transitions into "reality testing" (RT), improving the discrimination between the real and the inferred stimuli, a trait commonly impaired in psychotic-like states. Irene, a second-year PhD student, will show the establishment of a light-tone sensory preconditioning task in male mice, and also a RT protocol. Interestingly, results show that an acute injection of delta-9-tetrahydrocannabinol prior the ML test, disrupted RT in a cannabinoid receptor-1 (CB1R)-dependent manner. Ultimately, her goal is to identify novel therapeutic targets for cannabis-induced psychotic-like states.
