Bisgaardhan5810

lly gate sensory throughput to higher brain centers.17β-Estradiol (E2) is produced from androgens via the action of the enzyme aromatase. E2 is known to be made in neurons in the brain, but the functions of neuron-derived E2 in the ischemic brain are unclear. Here, we used a forebrain neuron-specific aromatase KO (FBN-ARO-KO) mouse model to deplete neuron-derived E2 in the forebrain and determine its roles after global cerebral ischemia. We demonstrated that ovariectomized female FBN-ARO-KO mice exhibited significantly attenuated astrocyte activation, astrocytic aromatization, and decreased hippocampal E2 levels compared with FLOX mice. Furthermore, FBN-ARO-KO mice had exacerbated neuronal damage and worse cognitive dysfunction after global cerebral ischemia. Similar results were observed in intact male mice. RNA-seq analysis revealed alterations in pathways and genes associated with astrocyte activation, neuroinflammation, and oxidative stress in FBN-ARO-KO mice. The compromised astrocyte activation in FBN-ARO-KO mice was associated with robust downregulationr understanding of this process by demonstrating that neuron-derived 17β-estradiol (E2) is neuroprotective and critical for induction of reactive astrocytes and their ability to produce astrocyte-derived neurotrophic factors, BDNF and IGF-1, and the glutamate transporter, GLT-1 after ischemic brain damage. These beneficial effects of neuron-derived E2 appear to be due, at least in part, to suppression of neuronal FGF2 signaling, which is a known suppressor of astrocyte activation. These findings suggest that neuron-derived E2 is neuroprotective after ischemic brain injury via a mechanism that involves suppression of neuronal FGF2 signaling, thereby facilitating astrocyte activation.Leptin signaling within the nucleus of the solitary tract (NTS) contributes to the control of food intake, and injections of leptin into the NTS reduce meal size and increase the efficacy of vagus-mediated satiation signals. Leptin receptors (LepRs) are expressed by vagal afferents as well as by a population of NTS neurons. However, the electrophysiological properties of LepR-expressing NTS neurons have not been well characterized, and it is unclear how leptin might act on these neurons to reduce food intake. Oprozomib in vivo To address this question, we recorded from LepR-expressing neurons in horizontal brain slices containing the NTS from male and female LepR-Cre X Rosa-tdTomato mice. We found that the vast majority of NTS LepR neurons received monosynaptic innervation from vagal afferent fibers and LepR neurons exhibited large synaptic NMDA receptor (NMDAR)-mediated currents compared with non-LepR neurons. During high-frequency stimulation of vagal afferents, leptin increased the size of NMDAR-mediated currents, but not A NTS neurons increases food intake. However, little was known about how leptin acts in the NTS neurons to inhibit food intake. We found that leptin increases the sensitivity of LepR-expressing neurons to vagal inputs by increasing NMDA receptor-mediated synaptic currents and that NTS NMDAR activation contributes to leptin-induced reduction of food intake. These findings suggest a novel mechanism by which leptin, acting in the NTS, could potentiate gastrointestinal satiation signals.The hippocampus plays an essential role in learning. Each of the three major hippocampal subfields, dentate gyrus (DG), CA3, and CA1, has a unique function in memory formation and consolidation, and also exhibit distinct local field potential (LFP) signatures during memory consolidation processes in non-rapid eye movement (NREM) sleep. The classic LFP events of the CA1 region, sharp-wave ripples (SWRs), are induced by CA3 activity and considered to be an electrophysiological biomarker for episodic memory. In LFP recordings along the dorsal CA1-DG axis from sleeping male mice, we detected and classified two types of LFP events in the DG high-amplitude dentate spikes (DSs), and a novel event type whose current source density (CSD) signature resembled that seen during CA1 SWR, but which, most often, occurred independently of them. Because we hypothesize that this event type is similarly induced by CA3 activity, we refer to it as dentate sharp wave (DSW). We show that both DSWs and DSs differentially modulate theat the DG is directly affected by memory consolidation processes. DSWs may thus complement SWRs as a sensitive electrophysiological biomarker of memory consolidation in mice.Cortical inhibition plays an important role in information processing in the brain. However, the mechanisms by which inhibition and excitation are coordinated to generate functions in the six layers of the cortex remain unclear. Here, we measured laminar-specific responses to stimulus orientations in primary visual cortex (V1) of awake monkeys (male, Macaca mulatta). We distinguished inhibitory effects (suppression) from excitation, by taking advantage of the separability of excitation and inhibition in the orientation and time domains. We found two distinct types of suppression governing different layers. Fast suppression (FS) was strongest in input layers (4C and 6), and slow suppression (SS) was 3 times stronger in output layers (2/3 and 5). Interestingly, the two types of suppression were correlated with different functional properties measured with drifting gratings. FS was primarily correlated with orientation selectivity in input layers (r = -0.65, p less then 10-9), whereas SS was primarily correlatal principles in macaque V1, but also provide a framework for general computation of cortical laminae in other sensory cortices.The human cerebellum is thought to interact with distributed brain networks to support cognitive abilities such as episodic memory and semantic prediction. Hippocampal and fronto-temporo-parietal networks that respectively support episodic memory versus semantic prediction have been associated with distinct endogenous oscillatory activity frequency bands theta (∼3-8 Hz) versus beta (∼13-30 Hz) respectively. We sought to test whether it is possible to toggle cerebellar participation in episodic memory versus semantic prediction by noninvasively stimulating with theta versus beta rhythmic transcranial magnetic stimulation. In human subjects of both sexes, cerebellar theta stimulation improved episodic memory encoding but did not influence neural signals of semantic prediction, whereas beta stimulation of the same cerebellar location increased neural signals of semantic prediction but did not influence episodic memory encoding. This constitutes evidence for double dissociation of cerebellar contributions to semantic prediction versus episodic memory based on stimulation rhythm, supporting the hypothesis that the cerebellum can be biased to support these distinct cognitive abilities at the command of network-specific rhythmic activity.