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Impact of neuroinflammation of contextual memory and neuronal circuit activity

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Impact of neuroinflammation on contextual memory and neuronal circuit activity in rats

Data from Dr. John Guzowski, University of California, Department of Neurobiology and The Center for the Neurobiology of Learning and Memory (CNLM)

Neuroinflammation is implicated in cognitive deficits associated with aging, disease, and trauma. Recently, the Guzowski laboratory demonstrated that systemic administration of the bacterial endotoxin lipopolysaccharide (LPS) elevates mRNA expression of the proinflammatory cytokines IL-1β, TNF-α, and IL-6 in the rat brain, produces specific memory retrieval deficits in context discrimination, and alters neural circuit activity in the hippocampus (Czerniawski & Guzowski, 2014; Czerniawski et al., 2015). The proinflammatory cytokines can have a peripheral source but can also be produced centrally by microglia and astrocytes. To test whether microglial release of cytokines drives alterations of neural circuit activity and cognitive deficits, they blocked microglial activation with systemic administration of minocycline, a semi-synthetic tetracycline antibiotic.

Rats were trained in a contextual memory task called context discrimination conditioning (CDC). Essentially, the rats were placed into two similar behavioral chambers (context A and context A’) daily during the training portion of the experiment. Context A was paired with a brief, mild footshock.

Upon reaching discrimination criterion, each subject received an intraperitoneal (i.p.) injection of minocycline (50 mg/kg) or saline and a second identical dose the next day. Thirty minutes after the second dose of minocycline or saline, LPS (150 μg/kg, i.p.) or saline was administered 6 h prior to testing in each of the contexts.

The experimental data generated for analyses are:

  • CDC training data; context A and context A’ freezing values and context order for each training day

  • CDC testing data; context A and context A’ freezing values for the testing session

  • Relative levels of dorsal hippocampal (dHPC) proinflammatory cytokines

  • Neuronal circuity activity in the dHPC

Here we present the transparent and reproducible analysis of the experimental data.