Survival analysis, mean accuracy scores and strategy index scores for each block.

<p>Survival analysis is shown as percentage of subjects remaining in the learning phase (A) and the reverse phase (B) as a function of number of trials completed. Accuracy is shown as percentage correct Genotypes (ephrinA2−/knockout  =  KO; wildtype  =  WT) and body weight restriction groups (90% and 80% of free-feeding weight) are represented separately. Error bars represent the standard error of the mean.</p

Behavioural results (% accuracy) and average spine density for all mice

<p>Column 1: Mouse ID<br>Column 2: Genotype (0=ephrin-A2-/-; 1=WT)<br>Column 3: Stimulation condition (1=sham; 2=rTMS)<br>Column 4: Gender (0=female; 1=male);<br>Column 5: Stripe orientation (0=horizontal; 1=vertical)<br>Column 6: Learning phase early (% accuracy)<br>Column 7: Learning phase mid (% accuracy)<br>Column 8: Learning phase late (% accuracy)<br>Column 9: Reverse learning phase early (% accuracy)<br>Column 10: Reverse learning phase mid (% accuracy)<br>Column 11: Reverse learning phase late (% accuracy)<br>Column 12: Dentate gyrus molecular layer, mean spine density per 10 micrometer<br>Column 13: CA1 pyramidal layer, mean spine density per 10 micrometer</p

Mean accuracy scores for sets of 10 trials.

<p>Results are shown separately for the learning (A) and reverse phases (B). Genotypes (ephrinA2−/knockout  =  KO; wildtype  =  WT) and body weight restriction groups (90% and 80% of free-feeding weight) are represented separately. Error bars represent the standard error of the mean.</p

LI-rTMS does not affect RGC survival or axonal regeneration following optic nerve crush.

<p>A: photomicrograph showing RGCs immunolabelled with β3 tubulin following an optic nerve crush and 2 weeks of daily LI-rTMS. Scale bar is 100 μm. B: Histogram showing counts of surviving RGCs in LI-rTMS and sham stimulated retinas 2 weeks following an optic nerve crush. There was no significant difference between the stimulation groups (p = 0.256). Error bars are standard error of the mean. C, D: GAP-43 immunohistochemistry in the proximal (C) and distal (D) optic nerve did not result in labelling of any axons. The crush site is indicated by *. Scale bar 100 μm</p

BDNF ELISA data.

<p>Daily LI-rTMS for 1 week does not increase BDNF levels in the retina or optic nerve of optic nerve crush or intact mice (p>0.05 for all groups; see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0126949#sec011" target="_blank">results</a> section). Histograms show BDNF levels as % of sham stimulated group. Error bars are standard error of the mean.</p

Effects of Neonatal Dexamethasone Exposure on Adult Neuropsychiatric Traits in Rats

<div><p>The effects of early life stress <i>in utero</i> or in neonates has long-term consequences on hypothalamic-pituitary-adrenal (HPA) stress axis function and neurodevelopment. These effects extend into adulthood and may underpin a variety of mental illnesses and be related to various developmental and cognitive changes. We examined the potential role of neonatal HPA axis activation on adult psychopathology and dopamine sensitivity in the mature rat using neonatal exposure to the synthetic glucocorticoid receptor agonist and stress hormone, dexamethasone. We utilized a comprehensive battery of assessments for behaviour, brain function and gene expression to determine if elevated early life HPA activation is associated with adult-onset neuropsychiatric traits. Dexamethasone exposure increased startle reactivity under all conditions tested, but decreased sensitivity of sensorimotor gating to dopaminergic disruption–contrasting with what is observed in several neuropsychiatric diseases. Under certain conditions there also appeared to be mild long-term changes in stress and anxiety-related behaviours with neonatal dexamethasone exposure. Electrophysiology revealed that there were no consistent neuropsychiatric abnormalities in auditory processing or resting state brain function with dexamethasone exposure. However, neonatal dexamethasone altered auditory cortex glucocorticoid activation, and auditory cortex synchronization. Our results indicate that neonatal HPA axis activation by dexamethasone alters several aspects of adult brain function and behaviour and may induce long-term changes in emotional stress-reactivity. However, neonatal dexamethasone exposure is not specifically related to any particular neuropsychiatric disease.</p></div

Diagrammatic representation of the study design.

<p>Mice received an optic nerve crush and were separated into two cohorts for (i) daily LI-rTMS or sham stimulation and assessed for RGC survival and axonal regeneration (2 weeks survival) (ii) quantification of BDNF levels by ELISA (1 week survival). With the second cohort, additional control groups of intact mice with no optic nerve crush were processed in parallel for BDNF analysis with the same LI-rTMS or sham stimulation parameters.</p

Electrophysiology recording and testing parameters.

<p>The auditory stimulus parameters, recording parameters, and outcome measures or each electrophysiology protocol.</p

Results from the prepulse inhibition of the startle reflex experiments.

<p>The habituation block of trials at the beginning and end of the experiment A) startle response to the habituation trials and B) the PPI response with and without dexamphetamine (AMPH). C) The baseline activity without startle pulses. D) The group average stimulus intensity–response magnitude curves for the startle response trials, with prepulse (dotted lines) or without prepulse (solid lines) curve fits. The parameters from curve fits to the startle only condition are shown in E) to I). E) R_MAX is the predicted maximum startle response and F) y₀ is the theoretical minimum startle response. G) The Threshold of sound intensity required to elicit a startle response. H) the logarithm of Hillslope, which is a measure of maximum velocity of the curve, where acceleration is 0. I) ES₅₀ the fitted value where startle response is half of maximum. Data were analysed using mixed model 3 or 2-way ANOVAs, as appropriate. Main effects of Dexamethasone treatment (DEX), Habituation block (Block), Amphetamine treatment (AMPH) and interactions are indicated by text within each panel. Bars show means and SEM. Comparison bars show post-hoc analysis Holm-Bonferroni t-tests. Significance values: *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.</p

Ages and timing of experiments.

<p>Each animal was tested at each age and for each task listed.</p