Synapses and circuits as targets of stress

Research in the Polter lab is focused on the neurobiological effects of stressful and adverse experiences. Our goal is to understand the mechanisms of stress-induced changes in synapses and circuits. We are particularly interested in synaptic regulation of neurons that produce monoamines-neurotransmitters such as dopamine and serotonin that are important modulators of affective and reward-related behavior. We use slice electrophysiology, coupled with retrograde tracers and viral-mediated optogenetics, and fiber photometry to identify and characterize circuit-specific alterations in synaptic plasticity and function following stress. We then use in vivo chemogenetics, pharmacology and optogenetics to reverse stress-induced neurobiological changes and maladaptive behavioral responses. 

Interactions of stress and sex in the VTA microcircuit

Individuals can vary greatly in their response to identical stressors. These responses can be modulated by factors such as sex and age. Our current work, funded by the NIMH and the Brain and Behavior Research Foundation, focuses on the role sex plays in determining both adaptive and maladaptive responses to stress. We use several different mouse stress paradigms in which males and females exhibit sexually dimorphic behavioral responses. We know that dopaminergic neurons are dynamically regulated by stress and are important in determining the behavioral adaptations after stress. VTA GABAergic neurons are crucial regulators of VTA dopaminergic neurons, and we are currently investigating the roles these neurons play in regulating sex differences in dopaminergic activity and hedonic, social, and anxiety-like behavior after stress. 

Early Life experience and maturation of the dorsal raphe

Serotonergic neurons originating the dorsal raphe project widely throughout the forebrain and are involved in controlling many aspects of behavior including locomotion, anxiety, cognition, and reward. These neurons are tightly regulated by synaptic inputs and by local GABAergic neurons. Activity of serotonergic and GABAergic neurons in the dorsal raphe fluctuates throughout the juvenile and adolescent period. Activity of these cells is tightly regulated by activity of prefrontal projections that target both GABAergic and serotonergic neurons. In this project, funded by a Discovery Pilot Award from CTSI-Children’s National, Our goal is to investigate the maturation of this feed-forward circuit and the role it plays in the development of coping responses in the face of stress. We are particularly interested in mechanisms by which early life experiences shape the maturation of these circuits.