Publications by Edgar Soria Gomez

Review: "The Disappointment Dilemma: Short- and Long-Term Learning From Negative Outcomes"

• Authors: Ibañez-Tallon, I (Ibanez-Tallon, Ines) ; Molas, S (Molas, Susanna) ; Proulx, C (Proulx, Christophe D.) ; Piriz, J (Piriz, Joaquin) ; Soria-Gómez, E (Soria-Gomez, Edgar)

• Publication date: 2026 May

• Abstract: In this review, we synthesize key findings from the 2025 Spanish Society for Neuroscience (SENC) symposium "Understanding Habenulae Function in Emotional Behavior" and propose that the brain possesses a "disappointment circuit" that complements the classic dopaminergic reward system. The "disappointment dilemma" in financial investing-avoiding risk to prevent short-term disappointment, only to later experience greater long-term disappointment when safe choices underperform-illustrates how immediate and delayed negative outcomes can be traded off over time. We argue that this dilemma parallels partially specialized roles of the lateral habenula (LHb), which signals immediate disappointments as acute negative prediction errors, and the medial habenula (MHb), which shapes longer-lasting negative expectations or mood through the accumulation of disappointing experiences over time. We propose that LHb outputs implement fast, trial-by-trial adjustments in coping strategies via RMTg- and VTA-projecting pathways, whereas MHb-IPN circuits gradually reshape threat valuation, withdrawal states, and mood across repeated disappointing or stressful experiences. We discuss how LHb and MHb circuits contribute to short- and long-term disappointment by integrating information on stress resilience, aversive learning, threat and fear responses, drug-related behaviors, and mood adaptation from specific cell types and receptors that modulate fear, addiction, and motivation to circuit-level mechanisms underlying aversive learning and emotional responses.

• Authors: Fedorov, D (Fedorov, Dmitry) ; Campillo, F (Campillo, Fabien) ; Desroches, M (Desroches, Mathieu) ; Soria-Gómez, E (Soria-Gomez, Edgar) ; Rodrigues, S (Rodrigues, Serafim) ; Piriz, J (Piriz, Joaquin)

• Publication date: 2026 April

• Abstract: The lateral habenula (LHb) is a small brain structure specialized in encoding aversive signals. Elevated bursting in the LHb has been linked to depressive-like behaviours in animal models. Bursting is a complex dynamic process that has been extensively studied and modelled in neuronal contexts. However, in the LHb, bursting activity has typically been described only as transient periods of high-frequency firing. Here, to provide a deeper understanding of LHb bursting, we analysed it from the perspective of dynamical systems. Ex vivo, LHb neurons display a variety of bursting patterns, characterized at one extreme by square wave-like bursts and at the other by parabolic bursts, plus transitional forms referred to as triangular bursts. Notably, these bursting patterns, which reflect different LHb output modes, can occur within the same neuron, reflecting distinct dynamic states. In particular, membrane hyperpolarization selectively promotes square-wave-type bursts, rather than triangular or parabolic ones. To capture these complex behaviours, we propose an idealized multiple-timescale dynamical model. This model successfully reproduces the three main bursting patterns observed in experimental data. Furthermore, we identify a special point in the parameter space, termed the saddle-node homoclinic bifurcation, which acts as an organizing centre demarcating the boundary between the two primary bursting patterns and around which the third pattern appears. Our model suggests that LHb bursting activity is structured around distinct dynamic states with potentially diverse and unexplored impacts on mood regulation. By providing new insights into the principles underlying LHb bursting, this framework may advance our understanding of its biological significance.Key points Bursting activity of the brain nucleus of the lateral habenula has been linked to depressive states. Using brain slice experiments, we identified three key burst types: square wave-like, parabolic and intermediate 'triangular' patterns. These patterns likely represent different functional modes of the same neuron rather than different neuron types. A mathematical model was developed that replicates these patterns and reveals a critical transition point that organizes their dynamics. This framework offers new insight into how LHb bursting activity is organized and could potentially guide future treatments for depression.

• Authors: Egaña-Huguet, J (Egana-Huguet, Jon) ; Sangroniz-Beltrán, L (Sangroniz-Beltran, Lucia) ; Baraibar, AM (Baraibar, Andres M.) ; Reyes-Velásquez, P (Reyes-Velasquez, Pablo) ; Landgraf, NF (Landgraf, Nicolas F.) ; Torres-Maldonado, P (Torres-Maldonado, Paula) ; Rodríguez-Cedrés, C (Rodriguez-Cedres, Cathaysa) ; Julio-Kalajzic, F (Julio-Kalajzic, Francisca) ; Piriz, J (Piriz, Joaquin) ; Ramos, A (Ramos, Almudena) ; Grandes, P (Grandes, Pedro) ; Marsicano, G (Marsicano, Giovanni) ; Mato, S (Mato, Susana) ; Ceprián, M (Ceprian, Maria) ; Soria-Gómez, E (Soria-Gomez, Edgar)

• Publication date: 2026 Mar

• Abstract: Background Navigation and memory are hippocampal functions that are essential for survival. One of the key modulators of hippocampal activity is the endocannabinoid system through the cannabinoid receptor type 1 (CBI). CB1 is widely expressed in various types of hippocampal cells. While it is known that CB1 participates in memory processes, its specific roles in different cell types and differences between sexes remain unclear.

• Methods: This study investigates the cell-and sex-specific modulation of navigation and memory by CB1 receptors. To this end, we selectively deleted CB1 receptors from hippocampal neurons or astrocytes in adult male and female mice. We then assessed its effect on a comprehensive range of behaviors, including innate emotional responses, memory, navigation, and nesting.

• Results: Deletion of CB1 from hippocampal principal cells or astrocytes produced significant changes in innate emotional behavior and novel object recognition in both sexes. Conversely, CB1 receptor deletion from all neurons produced deficits in spatial navigation exclusively in males. Interestingly, synaptic plasticity was impaired in both male and female mice lacking CB1 receptors from GFAP-positive cells. Nest-building behavior was only affected in males carrying the CBI deletion in CAMK-positive cells.

• Conclusion: In conclusion, our findings show that neuronal CB1 receptors are critical for spatial navigation in males, while astrocytic CB1 receptors play a key role in memory processes in both males and females.

• Authors: Zottola, ACP (Zottola, Antonio C. Pagano) ; Martín-Jiménez, R (Martin-Jimenez, Rebeca) ; Lavanco, G (Lavanco, Gianluca) ; Hamel-Coté, G (Hamel-Cote, Genevieve) ; Ramon-Duaso, C (Ramon-Duaso, Carla) ; Rodrigues, RS (Rodrigues, Rui S.) ; Mariani, Y (Mariani, Yamuna) ; Khan, M (Khan, Mehtab) ; Drago, F (Drago, Filippo) ; Jean, S (Jean, Stephanie) ; Rio, IBD (Rio, Itziar Bonilla-Del) ; Jimenez-Blasco, D (Jimenez-Blasco, Daniel) ; Egaña-Huguet, J (Egana-Huguet, Jon) ; Eraso-Pichot, A (Eraso-Pichot, Abel) ; Beriain, S (Beriain, Sandra) ; Cannich, A (Cannich, Astrid) ; Vidal-Palencia, L (Vidal-Palencia, Laura) ; Infantino, R (Infantino, Rosmara) ; Julio-Kalajzic, F (Julio-Kalajzic, Francisca) ; Gisquet, D (Gisquet, Doriane) ; Goncalves, A (Goncalves, Ania) ; Al-Younis, I (Al-Younis, Inas) ; Baussan, Y (Baussan, Yann) ; Duvezin-Caubet, S (Duvezin-Caubet, Stephane) ; Devin, A (Devin, Anne) ; Soria-Gomez, E (Soria-Gomez, Edgar) ; Puente, N (Puente, Nagore) ; Bolaños, JP (Bolanos, Juan P.) ; Grandes, P (Grandes, Pedro) ; Pouvreau, S (Pouvreau, Sandrine) ; Busquets-Garcia, A (Busquets-Garcia, Arnau) ; Marsicano, G (Marsicano, Giovanni) ; Bellocchio, L (Bellocchio, Luigi) ; Hebert-Chatelain, E (Hebert-Chatelain, Etienne) 

• Publication date: 2025 Sep

• Abstract: Many brain disorders involve mitochondrial alterations, but owing to the lack of suitable tools, the causal role of mitochondrial dysfunction in pathophysiological processes is difficult to establish. Heterotrimeric guanine nucleotide-binding (G) proteins are key regulators of cell functions, and they can be found within mitochondria. Therefore, we reasoned that the activation of stimulatory mitochondrial G proteins (Gs) could rapidly promote the activity of the organelle and possibly compensate for bioenergetic dysfunction. Here, we show that a mitochondria-targeted recombinant designer receptor exclusively activated by designer drugs (mitoDREADD-Gs) can acutely trigger intramitochondrial signaling to increase mitochondrial membrane potential and oxygen consumption. In vivo activation of mitoDREADD-Gs abolished memory alterations in cannabinoid-treated mice and in two mouse models of Alzheimer's disease and frontotemporal dementia. Thus, mitoDREADD-Gs enables the establishment of causal relationships between mitochondria and biological or disease-related processes and represents an innovative potential therapeutic approach for disorders associated with mitochondrial impairment.

• Authors: Serrano, M (Serrano, Maitane) ; Saumell-Esnaola, M (Saumell-Esnaola, Miquel) ; Ocerin, G (Ocerin, Garazi) ; del Caño, GG (Garcia del Cano, Gontzal) ; Soria-Gómez, E (Soria-Gomez, Edgar) ; Mimenza, A (Mimenza, Amaia) ; Puente, N (Puente, Nagore) ; Bonilla-Del Río, I (Bonilla-Del Rio, Itziar) ; Ramos-Uriarte, A (Ramos-Uriarte, Almudena) ; Reguero, L (Reguero, Leire) ; Christie, BR (Christie, Brian R.) ; de Fonseca, FR (de Fonseca, Fernando Rodriguez) ; Rodríguez-Arias, M (Rodriguez-Arias, Marta) ; Gerrikagoitia, I (Gerrikagoitia, Inmaculada) ; Grandes, P (Grandes, Pedro)

• Publication date: 2025 Jun

• Abstract: Adolescent binge drinking has lasting behavioral consequences by disrupting the endocannabinoid system (ECS) and depleting brain omega-3. The natural accumulation of omega-3 fatty acids in cell membranes is crucial for maintaining the membrane structure, supporting interactions with the ECS, and restoring synaptic plasticity and cognition impaired by prenatal ethanol (EtOH) exposure. However, it remains unclear whether omega-3 supplementation can mitigate the long-term effects on the ECS, endocannabinoid-dependent synaptic plasticity, and cognition following adolescent binge drinking. Here, we demonstrated that omega-3 supplementation during EtOH withdrawal increases CB1 receptors in hippocampal presynaptic terminals of male mice, along with the recovery of receptor-stimulated [35S]GTP gamma S binding to G alpha i/o proteins. These changes are associated with long-term potentiation (LTP) at excitatory medial perforant path (MPP) synapses in the dentate gyrus (DG), which depends on anandamide (AEA), transient receptor potential vanilloid 1 (TRPV1), and N-methyl-D-aspartate (NMDA) receptors. Finally, omega-3 intake following binge drinking reduced the time and number of errors required to locate the escape box in the Barnes maze test. Collectively, these findings suggest that omega-3 supplementation restores Barnes maze performance to levels comparable to those of control mice after adolescent binge drinking. This recovery is likely mediated by modulation of the hippocampal ECS, enhancing endocannabinoid-dependent excitatory synaptic plasticity.

• Authors: Preciado, MM (Martinez Preciado, M.) ; Gaminde-Blasco, A (Gaminde-Blasco, A.) ; Balantzategi, U (Balantzategi, U.) ; Soria-Gomez, E (Soria-Gomez, E.) ; Capetillo-Zarate, E (Capetillo-Zarate, E.) ; Alberdi, E (Alberdi, E.)

• Publication date: 2025 Jun

• Authors: Sangroniz-Beltran, L (Sangroniz-Beltran, L.) ; Ceprian, M (Ceprian, M.) ; Egaña-Huguet, J (Egana-Huguet, J.) ; Fedorov, D (Fedorov, D.) ; Santas-Martin, JA (Santas-Martin, J. A.) ; Rodriguez-Cedres, C (Rodriguez-Cedres, C.) ; Landgraf, N (Landgraf, N.) ; Reyes-Velasquez, P (Reyes-Velasquez, P.) ; Ducourneau, E (Ducourneau, E.) ; Ramos-Miguel, A (Ramos-Miguel, A.) ; Piriz, J (Piriz, J.) ; Grandes, P (Grandes, P.) ; Marsicano, G (Marsicano, G.) ; Ferreira, G (Ferreira, G.) ; Mato, S (Mato, S.) ; Soria-Gomez, E (Soria-Gomez, E.) 

• Publication date: 2025 Jun

• Authors: Baraibar, AM (Baraibar, A. M.) ; Colomer, T (Colomer, T.) ; Moreno-García, A (Moreno-Garcia, A.) ; Bernal-Chico, A (Bernal-Chico, A.) ; Sánchez-Martín, E (Sanchez-Martin, E.) ; Utrilla, C (Utrilla, C.) ; Serrat, R (Serrat, R.) ; Soria-Gómez, E (Soria-Gomez, E.) ; Rodríguez-Antigueedad, A (Rodriguez-Antigueedad, A.) ; Araque, A (Araque, A.) ; Matute, C (Matute, C.) ; Marsicano, G (Marsicano, G.) ; Mato, S (Mato, S.)

• Publication date: 2024 Oct

• Abstract: Cortical pathology involving inflammatory and neurodegenerative mechanisms is a hallmark of multiple sclerosis and a correlate of disease progression and cognitive decline. Astrocytes play a pivotal role in multiple sclerosis initiation and progression but astrocyte-neuronal network alterations contributing to gray matter pathology remain undefined. Here we unveil deregulation of astrocytic calcium signaling and astrocyte-to-neuron communication as key pathophysiological mechanisms of cortical dysfunction in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Using two-photon imaging ex vivo and fiber photometry in freely behaving mice, we found that acute EAE was associated with the emergence of spontaneously hyperactive cortical astrocytes exhibiting dysfunctional responses to cannabinoid, glutamate and purinoreceptor agonists. Abnormal astrocyte signaling by Gi and Gq protein coupled receptors was observed in the inflamed cortex. This was mirrored by treatments with pro-inflammatory factors both in vitro and ex vivo, suggesting cell-autonomous effects of the cortical neuroinflammatory environment. Finally, deregulated astrocyte calcium activity was associated with an enhancement of glutamatergic gliotransmission and a shift of astrocyte-mediated short-term and long-term plasticity mechanisms towards synaptic potentiation. Overall, our data identify astrocyte-neuronal network dysfunctions as key pathological features of gray matter inflammation in multiple sclerosis and potentially additional neuroimmunological disorders.

• Authors: Irastorza-Valera, L (Irastorza-Valera, Luis) ; Soria-Gómez, E (Soria-Gomez, Edgar) ; Benitez, JM (Benitez, Jose Maria) ; Montáns, FJ (Montans, Francisco J.) ; Saucedo-Mora, L (Saucedo-Mora, Luis)

• Publication date: 2024 Jun

• Abstract: The brain is the most complex organ in the human body and, as such, its study entails great challenges (methodological, theoretical, etc.). Nonetheless, there is a remarkable amount of studies about the consequences of pathological conditions on its development and functioning. This bibliographic review aims to cover mostly findings related to changes in the physical distribution of neurons and their connections-the connectome-both structural and functional, as well as their modelling approaches. It does not intend to offer an extensive description of all conditions affecting the brain; rather, it presents the most common ones. Thus, here, we highlight the need for accurate brain modelling that can subsequently be used to understand brain function and be applied to diagnose, track, and simulate treatments for the most prevalent pathologies affecting the brain.

• Authors: Soria-Gómez, E (Soria-Gomez, Edgar) ; Piriz, J (Piriz, Joaquin) ; Torres-Alemán, I (Torres-Aleman, Ignacio)

• Publication date: 2024 May

• Authors: Serrano, M (Serrano, M.) ; Lekunberri, L (Lekunberri, L.) ; Saumell-Esnaola, M (Saumell-Esnaola, M.) ; Caño, GGD (Cano, G. Garcia-Del) ; Soria-Gomez, E (Soria-Gomez, E.) ; Mimenza, A (Mimenza, A.) ; Anaut-Lusar, I (Anaut-Lusar, I.) ; Bonilla-Del Río, I (Bonilla-Del Rio, I.) ; Egaña-Huguet, J (Egana-Huguet, J.) ; Sallés, J (Salles, J.) ; Gerrikagoitia, I (Gerrikagoitia, I.) ; Puente, N (Puente, N.) ; Elezgarai, I (Elezgarai, I.) ; Rico-Barrio, I (Rico-Barrio, I.) ; Grandes, P (Grandes, P.)

• Publication date: 2022 Jun

For a comprehensive overview of Edgar Soria's scientific contributions, extensive publication history, and citation metrics, please visit his official author record.