Animal Models of Psychiatric Disease

The focus of my team is on cognition and how it is affected by neuropsychiatric ailments, such as depression, addiction, and impulsivity. We study maladaptation of synapses and circuitry brought about by unique molecular signatures in hippocampus and prefrontal cortex.

Research focus

Cognitive malfunctioning is a hallmark of several psychiatric disorders. In post-traumatic stress disorder (PTSD), as well as addiction, memory plays a key role in development and persistence of the disease. Although malfunction of memory is secondary to major depression (MDD), it can pertain even upon remission of primary depression.

Learning & memory: We study the process of memory formation, reconsolidation and extinction using fear conditioning and molecular and cellular interventions of the dorsal hippocampus. In addition, we focus on how these processes depend on AMPA and NMDA receptor plasticity (including auxiliary subunits) using transgenic mice. See our latest contributions to the Shisa-team eLife paper., and the rest of the AMPA receptor auxiliary protein team’s Cell Reports paper on the role of Noelin1.

Depression: Using the paradigm of social defeat-induced persistent stress (SDPS), we study the persistent phase of depression. This means studying these animals weeks after the fight phase of social defeat (rats, mice), in the absence of acute physical stressors, as is evident for example from normalised corticosterone levels and body weight. Doing so, we focus on molecules that are related to the vulnerability to depression and treatment outcome, as well as comborbidity to alcohol use disorders. Our latest results shows involvement of the extracellular matrix, as can be viewed in our Science Translational Medicine paper.

Addiction: Together with Taco de Vries we use self-administration models to focus on the persistent memory that hijacks the reward system, as is evident from relapse by drug-associated cues. This addictive memory is studied for drugs of abuse like heroin, nicotine and alcohol.

Attention & impulsivity: We focus on mouse models for decreased inhibitory control. These mice show increased drug use. Together with Maarten Loos from Sylics, we screen mouse mutants for deficits in inhibitory control and attention using their high throughput 5-choice serial reaction time task.

This work is done in close collaboration with other teams: Michel van den Oever (optogenetics, molecular code of memory), Ka Wan Li (proteomics, glutamate receptor interactions), Mark Verheijen (glial plasticity), Taco de Vries (addiction), and Rhiannon Meredith & Huib Mansvelder (electrophysiology).

Team members:
• Priyanka Rao-Ruiz (Learning & memory; AMPA receptor regulation)

• Ioannis Kramvis (Hippocampal and PFC plasticity related to depression
• Danai Riga (Comorbidity of depression & alcohol use disorder; subtypes of depression, cognitive control)

PhD students:
• Demirhan Çetereisi (Plasticity related to orphan GPCR signaling, memory paradigms), CognitionNet trainee co-supervised by Ka Wan Li
• Maija-Kreta Koskinen (Mouse model of persistent depression, parvalbumin interneurons), CognitionNet trainee
• Elena Marchisella (Cognition, schizophrenia models, parvalbumin interneurons ), IN-SENS trainee, employed @ Sylics, supervised by Maarten Loos
• Azra E. Zamri (AMPAR auxiliary proteins; visiting student from the Choquet & Coussen lab)
• Yongmei (Sonya) Sun (Addiction and depression models)
• Leonidas Faliagkas (Adrenergic modulation of reconsolidation; co-supervised by Priyanka Rao-Ruiz)

Collaborating researchers:
• Remco V. Klaassen (Glutamate receptor modulation, Shisa proteins)

Rolinka J. van der Loo (Phenotyper, behavioral test battery (e.g. cognition, anxiety), intracranial cannulation, virus injection, optogenetics)

Former team members:
• Nikhil Pandya (Glutamate receptor interactions in learning and memory) currently at Roche, Basel.
• Leanne J.M. Schmitz (Learning & memory; AMPA & NMDA receptor regulation, Shisa proteins) currently at Catalyze.
• A. Mariette Lenselink (Glutamate excess and calcium channels in cognitive function) currently at LUMC, Leiden.
• Bart R. Lubbers (Extracellular matrix in drug addiction; nicotine relapse-specific protein regulation).
• Maarten Loos (Impulsivity & attention, genetic mouse model) currently at Synaptologics BV.
• Danielle S. Counotte (Adolescent nicotine, impulsivity & attention) currently working with Nutricia Research
• Pieter van Bokhoven (Depression model; treatment-specific protein regulation hippocampus), currently working at Amsterdam Neuroscience, Industry Alliance Office.
Michel C. van den Oever (drug addiction, relapse & abstinence), currently independent group leader at the CNCR.

Team Leader
Sabine Spijker