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Background: Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD. Aim: The present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m‐amph). Methods: Wistar rats were given 14 days of m‐amph injections, and on the last day, animals were submitted to 20 min of VTA DBS in two different patterns: intermittent low‐frequency stimulation (LFS) or continuous high‐frequency stimulation (HFS). Immediately after DBS, manic‐like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open‐field tests and fast‐scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry. Results: M‐amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. M‐amph increased DA reuptake time post‐sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc. Conclusion: These results demonstrate that both VTA LFS and HFS DBS exert anti‐manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti‐manic effects. [ABSTRACT FROM AUTHOR]

Descending auditory pathways can modify afferent auditory input en route to cortex. One component of these pathways is the olivocochlear system which originates in brainstem and terminates in cochlea. Medial olivocochlear (MOC) neurons also project collaterals to cochlear nucleus and make synaptic contacts with dendrites of multipolar neurons. Two broadly distinct populations of multipolar cells exist: T‐stellate and D‐stellate neurons, thought to project to inferior colliculus and contralateral cochlear nucleus, respectively. It is unclear which of these neurons receive direct MOC collateral input due to conflicting results between in vivo and in vitro studies. This study used anatomical techniques to identify which multipolar cell population receives synaptic innervation from MOC collaterals. The retrograde tracer Fluorogold was injected into inferior colliculus or cochlear nucleus to label T‐stellate and D‐stellate neurons, respectively. Axonal branches of MOC neurons were labeled by biocytin injections at the floor of the fourth ventricle. Fluorogold injections resulted in labeled cochlear nucleus multipolar neurons. Biocytin abundantly labeled MOC collaterals which entered cochlear nucleus. Microscopic analysis revealed that MOC collaterals made some putative synaptic contacts with the retrogradely labeled neurons but many more putative contacts were observed on unidentified neural targets. This suggest that both T‐ and D‐stellate neurons receive synaptic innervation from the MOC collaterals on their somata and proximal dendrites. The prevalence of these contacts cannot be stated with certainty because of technical limitations, but the possibility exists that the collaterals may also make contacts with neurons not projecting to inferior colliculus or the contralateral cochlear nucleus. [ABSTRACT FROM AUTHOR]

Following mild traumatic brain injury (mTBI), further mild impacts can exacerbate negative outcomes. To compare chronic damage and deficits following increasing numbers of repeated mTBIs, a closed‐head weight‐drop model of repeated mTBI was used to deliver 1, 2 or 3 mTBIs to adult female rats at 24 h intervals. Outcomes were assessed at 3 months following the first mTBI. No gross motor, sensory or reflex deficits were identified (p > 0.05), consistent with current literature. Cognitive function assessed using a Morris water maze revealed chronic memory deficits following 1 and 2, but not 3 mTBI compared to shams (p ≤ 0.05). Oxidative damage to DNA was assessed immunohistochemically in the dentate hilus of the hippocampus and splenium of the corpus callosum; no changes were observed. IBA1‐positive microglia were increased in size in the cortex following 1 mTBI and in the corpus callosum following 2 mTBI compared to shams (p ≤ 0.05); no changes were observed in the dentate hilus. Glial fibrillary acidic protein (GFAP)‐positive astrocyte immunoreactivity was assessed in all three brain regions and no chronic changes were observed. Integrity of myelin ultrastructure in the corpus callosum was assessed using transmission electron microscopy. G ratio was decreased following 2 mTBIs compared to shams (p ≤ 0.05) at post hoc level only. The changing patterns of damage and deficits following increasing numbers of mTBI may reflect dynamic responses to small numbers of mTBIs or a conditioning effect such that increasing numbers of mTBIs do not necessarily result in worsening pathology. Open science badges: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Cover Image for this issue: doi: 10.1111/jnc.14508. [ABSTRACT FROM AUTHOR]