Lindquist Laboratory

Research

My behavioral neuroscience research program is grounded in the neurobiology of learning and memory, specifically the brain regions, cell populations, and synaptic plasticity processes engaged by distinct associative (Pavlovian) learning paradigms. Using various behavioral paradigms, we examine CNS activation and function across four primary structures: the cerebellum, amygdala, hippocampus, and prefrontal cortex. For an informative discussion on learning and memory, listen to this NPR link.  Pregnant woman drinking wine

Our primary research focus relates to a rodent model of fetal alcohol spectrum disorders (FASD). During early postnatal life, a period comparable to the third trimester in humans, rat pups are exposed to various concentrations of ethanol (mixed in milk) and allowed to mature. We are interested in ethanol's neurotoxic effects on forebrain development, the hippocampus and medial prefrontal cortex in particular, and cognitive function. We have now established, in FASD model rats, dose-dependent deficits in two variants of Pavlovian fear conditioning, trace fear conditioning and one-trial contextual fear conditioning, as well as a simple recogntion memory task. The goal is to link behavioral impairments to a mechanistic account of alcohol’s deleterious effects on forebrain development, NMDA receptor composition and function, and synpatic plasticity (LTP/LTD). Results to date suggests the FASD model rats can learn new information—rather, they are impaired at the time of testing, owing to a weaker (i.e., less consolidated) long-term fear memory. We have also begun to examine the synergistic (but disruptive) relationship between early-life ethanol exposure and the ensuing neuroinflammation, both of which can disrupt neurodevelopment and learning-dependent synaptic plasticity. It is also possible neuroimmune signaling is persistently altered over development. Non-optimal concentrations of IL-1B, for instance, is known to impede long-term memory consolidation, consistent with our prior results in FASD rats. We are currently examining the efficiacy of various immunosuppressant drugs, administered concurrent with ethanol exposure or at the time of behavioral testing, to mitigate neuroinflammation and rescuse cognitive function in adolescent and adult FASD rats. Our focus is on ethanol-mediated activation of brain-resident mast cells and microglia.

Experimentally, the lab utilizes a variety of techniques, including multiple behavioral assays, survival surgery (lesions, cannulae implants), neuropharmacology (systemic and local drug administration), neurophysiology (extracellular unit recordings), immunohistochemistry, Western Blotting, and unbiased stereology.