Iron delivery to the developing brain is essential for energy and metabolic support needed for processes such as myelination and neuronal development. Iron deficiency, especially in the developing brain, can result in a number of long‐term neurological deficits that persist into adulthood. There is considerable debate that excess access to iron during development may result in iron overload in the brain and subsequently predispose individuals to age‐related neurodegenerative diseases. There is a significant gap in knowledge regarding how the brain acquires iron during development and how biological variables such as development, genetics, and sex impact brain iron status. In this study, we used a mouse model expressing a mutant form of the iron homeostatic regulator protein HFE, (Hfe H63D), the most common gene variant in Caucasians, to determine impact of the mutation on brain iron uptake. Iron uptake was assessed using 59Fe bound to either transferrin or H‐ferritin as the iron carrier proteins. We demonstrate that at postnatal day 22, mutant mice brains take up greater amounts of iron compared with wildtype. Moreover, we introduce H‐ferritin as a key protein in brain iron transport during development and identify a sex and genotype effect demonstrating female mutant mice take up more iron by transferrin, whereas male mutant mice take up more iron from H‐ferritin at PND22. Furthermore, we begin to elucidate the mechanism for uptake using immunohistochemistry to profile the regional distribution and temporal expression of transferrin receptor and T‐cell immunoglobulin and mucin domain 2, the latter is the receptor for H‐ferritin. These data demonstrate that sex and genotype have significant effects on iron uptake and that regional receptor expression may play a large role in the uptake patterns during development. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/ Cover Image for this issue: doi: .

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Exposure to opioids reshapes future reward and motivated behaviors partially by altering the functional output of medium spiny neurons (MSNs) in the nucleus accumbens shell. Here, we investigated how morphine, a highly addictive opioid, alters synaptic transmission and intrinsic excitability on dopamine D1-receptor (D1R) expressing and dopamine D2-receptor (D2R) expressing MSNs, the two main output neurons in the nucleus accumbens shell. Using wholecell electrophysiology recordings, we show, that 24 h abstinence following repeated noncontingent administration of morphine (10 mg/kg, i.p.) in mice reduces miniature excitatory postsynaptic current (mEPSC) frequency and miniature inhibitory postsynaptic current (mIPSC) frequency on D2R-MSNs, with concomitant increases in D2R-MSN intrinsic membrane excitability. We did not observe any changes on synaptic or intrinsic changes on D1R-MSNs. Lastly, in an attempt to determine the integrated effect of the synaptic and intrinsic alterations on the overall functional output of D2R-MSNs, we measured the input-output efficacy by measuring synaptically-driven action potential firing. We found that both D1R-MSN and D2R-MSN output was unchanged following morphine treatment. 42 4 much lesser degree (Bertran-Gonzalez et al., 2008). Mice were singly-housed and maintained on 43 a regular 12 hour light/dark cycle (lights on 07:00, lights off 19:00) with ad libitum food and 44 water. 45 2.2. Drugs 46 (−)-morphine sulfate pentahydrate was provided by the National Institute on Drug Abuse Drug 47 Supply Program. NBQX and AP5 were purchased from Tocris Biosciences. Picrotoxin was 48 purchased from Sigma Aldrich. Tetrodotoxin (TTX) was purchased from Enzo. 49 2.3. Repeated systemic injections of saline or morphine 50 Before drug administration, mice were allowed to acclimate to their home cages for >5d. For 51 drug treatment, we used a 5d repeated drug administration procedure (Huang et al., 52 2009;Graziane et al., 2016). In all electrophysiological experiments, once per d for 5d, mice were 53 taken out of the home cages for an intraperitoneal (i.p.) injection of either (−)-morphine sulfate 54 pentahydrate (10mg/kg in 0.9% saline) or the same volume of 0.9% saline, and then placed back 55 to the home cage at ~Zeitgeber time (ZT) 2 (ZT0=lights on, ZT12=lights off). Animals were 56 randomly selected for each drug treatment. Morphine-or saline-treated animals were then used 57 for electrophysiological recordings ~24h following the last injection.58 2.4. Acute Brain Slice Preparation 59 At ~ZT time 2, mice were deeply anesthetized with isoflurane and cardiac perfused with an ice-60 cold NMDG-based cutting solution containing (in mM): 135 N-methyl-d-glutamine, 1 KCl, 1.2 61 KH2PO4, 0.5 CaCl2, 1.5 MgCl2, 20 choline-HCO3, and 11 glucose, saturated with 62 95%O2/5%CO2, adjusted to a pH of 7.4 with HCl, osmolality adjusted to 305 mmol/kg. 63Following perfusion, mice were decapitated and brains were rapidly removed. 250 m coronal 64 brain slices containing the nucleus accumbens shell were prepared ...

The paraventricular thalamic nucleus (PVT) is a brain region involved in regulating arousal, goal-oriented behaviors, and drug seeking, all key factors playing a role in substance use disorder. Given this, we investigated the temporal effects of administering morphine, an opioid with strongly addictive properties, on PVT neuronal function in mice using acute brain slices.