Specific programme: NEURON COFUND 2 2023

The objective of the call is to facilitate multinational and collaborative research projects that address critical transnational issues to improve our knowledge on the neurobiological mechanisms involved in the mechanisms of resilience and vulnerability to environmental challenges in mental health.

Project PCI2024-153463 funded by MICIU/AEI /10.13039/501100011033 and Co-financed by the European Union.

APCIN code: PCI2024-153463

UPV/EHU: IP beneficiary

UPV/EHU: Shira Knafo

Project start: 01/04/2024

Project end: 31/03/2027

Brief description: Mental health disorders, particularly Major Depressive Disorder or anxiety disorders, are among the most important health problems worldwide, causing severe individual suffering and an enormous socioeconomic burden on society. Since the onset and progression of both disorders are highly influenced by contextual factors, the main idea of ​​the EnviroMood project is that plasticity is an underlying mechanism in both resilience and vulnerability, depending on the environmental context.

Based on findings from animal and human research, we postulate that it is environmental valence that determines whether brain networks are directed towards resilience or vulnerability, and plasticity states determine to what extent these environmental effects become permanent.

To this end, EnviroMood will use a back-translation approach to elucidate the interplay between environment, plasticity and behaviour as well as their underlying mechanisms: Starting from a proof-of-concept trial in humans and network analysis, we will test a differential modulation of mood by positively and negatively valenced behavioural interventions in different plasticity states. Furthermore, we will use plasticity stimulus-response methods to verify the effect of depression or drugs on plasticity correlates in humans (WP1). We will then back-translate this approach to animal models in rodents and assess behavioural vulnerability and resilience in mice under standardised conditions (IntelliCages) under different environmental conditions and plasticity-related drug treatment (WP2). Central monitoring of behavioural experiments in the IntelliCages will enable a high standardisation of behavioural experiments and animal models. To assess plasticity, we will measure synaptic plasticity in the hippocampus and amygdala in brain slices from these animals (WP3). In addition, we assess drug effects on AMPAR expression, spine, and network plasticity using state-of-the-art in vitro approaches (WP4). To elucidate the underlying mechanisms of the interaction between environment, plasticity, and behavior, we will use behavioral and ex vivo experiments of animals treated in IntelliCages and focus on the role of the TrkB pathway (WP5), amygdala (WP6), and microglia (WP7). We will use psychedelics (compared to SSRIs and ketamine from previous experiments) to increase and benzodiazepines to decrease plasticity. A deeper understanding of the interaction between environment, plasticity, and behavior will lead to the development of innovative interventions to increase resilience, decrease vulnerability, and promote mental health.

Project PCI2024-153463 funded by MICIU/AEI /10.13039/501100011033 and Co-financed by the European Union.