Parameters That Affect Fear Responses in Rodents and How to Use Them for Management

The strong innate fear response shown by laboratory rodents to predator cues could provide powerful and innovative tools for pest management. Predator cues are routinely used to induce fear and anxiety in laboratory rodents for pharmacological studies. However, research on the fear response induced by predator cues in different species of rodents in the wild has been inconclusive with results often contradictory to laboratory experiments. Potential explanations for this inconsistency include the prey's: (i) physiological state; (ii) parasite load; (iii) differential intensity of perceived threats; (iv) fear learning and habituation; and (v) information gathering. In this review, we first explore current knowledge on the sensory mechanisms and capabilities of rodents, followed by the discussion of each of these explanations within the context of their implications for the use of antipredator response as a pest rodent management tool. Finally, we make recommendations on potential solutions and strategies to resolve issues in rodent management related to these hypotheses

Genetic, molecular, and neurobiological determinants of post-traumatic stress disorder-related behaviour in mice

Post-traumatic stress disorder (PTSD), a debilitating mental health condition, can occur as a consequence of exposure to a traumatic, potentially life-threatening event or series of events. Debilitating intrusive thoughts, hyperarousal, and negative alterations to cognition and mood are symptoms that persist over time, often becoming progressively worse. The modest efficacy of treatment options for PTSD highlights a crisis in PTSD drug development necessitating the discovery of novel pharmacological drug targets. One potential target is microglia, the brains immune cells, which are implicated in stress responses and dendritic spine remodelling and may explain grey matter reductions in PTSD. We report elevated densities of hyper-ramified microglial cells across stress-responsive corticolimbic structures coinciding with neuronal dendritic spine loss 32 days after footshock. We then investigated genetic vulnerability for PTSD through deletion of P-glycoprotein (P-gp), a transporter regulating brain uptake of corticosteroid stress hormones. P-gp knockout (KO) increased depression and anxiety-related behaviours, however, decreased conditioned fear responses following footshock. Independent of genotype, footshock decreased microglial density in several amygdaloid nuclei. Irrespective of footshock, P-gp KO led to an increased number of hypo-ramification microglia in the CA3. Finally, we investigated the effect of genetic deletion of P2x7, a receptor predominantly localised on microglia regulating release of IL-1β. This cytokine is associated with depression, bipolar disorder, and heightened aggression. P2X7 KO reduced aggression in mice, however this did not coincide with changes to microglial cell densities. P2X7 receptor deletion also decreased obsessive-compulsive behaviours, often a co-morbid diagnosis with PTSD. The P2X7 receptor, therefore, may serve as a novel target for serenic therapeutics for treatment of PTSD arousal and reactivity

Demographic and depression characteristics stratified by age.

<p>HDRS: Hamilton Depression Rating Scale total score, SD: standard variation.</p

Circadian parameters of the activity-rest cycle derived from Cosinor analyses.

<p>Horizontal bars indicate significant differences across specific age groups. Horizontal bars indicate significant depression severity effects. No significant interaction was found between age and depression severity. *p<.050.</p

Multiple regression model showing the contributions of age and depressive symptoms severity to sleep-wake cycle disturbances.

<p>Beta (β) values from multiple regression analyses and full model statistics. HDRS: Hamilton Depression Rating Scale, SleepON: sleep onset, SleepOFF: sleep offset, TiB: time in bed, WASO: wake after sleep onset, SE: sleep efficiency. Predictor significance:</p><p>*p<.050,</p><p>**p<.010,</p><p>***p<.001.</p

Sleep-wake variables across age groups and depressive symptoms severity levels.

<p>Horizontal bars indicate significant differences across specific age groups. Horizontal bars indicate significant depression severity effects. No significant interaction was found between age and depression severity. *p<.050.</p

Example of activity cycle parameters derived from the extended Cosinor analysis.

<p>Each point represents a recording of activity intensity at a given time and the full line represents the fitted extended Cosinor curve. Nonlinear least-squares regression was used to fit actigraphy datasets to the model. The abscissa denotes time and the ordinate indicates activity intensity. Amplitude: difference between the peak and trough) of the fitted curve. Acrophase: time when the activity cycle reaches peak value. α: relative width of the curve at the middle of the peak. β: indicator of the steepness of the rise and fall of the curve. The coefficient of determination (or R²; not illustrated here), a measure reflecting the goodness of fit, was used as an indicator of circadian rhythmicity.</p

Comparisons of actigraphy variables across age and depression severity groups and associations with depression severity and age.

<p>Means, standard deviations (SD) and statistics for actigraphy variables across age groups and depression severity levels. HDRS: Hamilton Depression Rating Scale, Sleep_ON: sleep onset, Sleep_OFF: sleep offset, TiB: time in bed, TST: total sleep time, WASO: wake after sleep onset, SE: sleep efficiency, R²: circadian rhythmicity index.</p><p>*p<.050,</p><p>**p<.010,</p><p>***p<.001.</p