Hernandezlund0331

Mounting experimental evidence demonstrate that sex neuroactive steroids (neurosteroids) are essential for memory formation. Neurosteroids have a profound impact on the function and structure of neural circuits and their local synthesis is necessary for the induction of both long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission and for neural spine formation in different areas of the central nervous system (CNS). Several studies demonstrated that in the hippocampus, 17β-estradiol (E2) is necessary for inducing LTP, while 5α-dihydrotestosterone (DHT) is necessary for inducing LTD. VER155008 This contribution has been proven by administering sex neurosteroids in rodent models and by using blocking agents of their synthesis or of their specific receptors. The general opposite role of sex neurosteroids in synaptic plasticity appears to be dependent on their different local availability in response to low or high frequency of synaptic stimulation, allowing the induction of bidirectional synaptic plasticity. The relevant contribution of these neurosteroids to synaptic plasticity has also been described in other brain regions involved in memory processes such as motor learning, as in the case of the vestibular nuclei, the cerebellum, and the basal ganglia, or as the emotional circuit of the amygdala. The rapid effects of sex neurosteroids on neural synaptic plasticity need the maintenance of a tonic or phasic local steroid synthesis determined by neural activity but might also be influenced by circulating hormones, age, and gender. To disclose the exact mechanisms how sex neurosteroids participate in finely tuning long-term synaptic changes and spine remodeling, further investigation is required.Neonatal and infant exposure to volatile anesthetics has been associated with long-term learning, memory, and behavioral deficits. Although early anesthesia exposure has been linked to a number of underlying structural abnormalities, functional changes associated with these impairments remain poorly understood. To investigate the relationship between functional alteration in neuronal circuits and learning deficiency, resting state functional MRI (rsfMRI) connectivity was examined in adolescent rabbits exposed to general anesthesia as neonates (1 MAC isoflurane for 2 h on postnatal days P8, P11, and P14) and unanesthetized controls before and after training with a trace eyeblink classical conditioning (ECC) paradigm. Long-range connectivity was measured between several key regions of interest (ROIs), including primary and secondary somatosensory cortices, thalamus, hippocampus, and cingulate. In addition, metrics of regional BOLD fluctuation amplitudes and coherence, amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) were calculated. Our results showed that the trace ECC learning rate was significantly lower in the anesthesia-exposed group. No anesthesia-related changes in long-range connectivity, fALFF, or ReHo were found between any ROIs. However, ALFF was significantly higher in anesthesia-exposed rabbits in the primary and secondary somatosensory cortices, and ALFF in those areas was a significant predictor of the learning performance for trace ECC. The absence of anesthesia-related changes in long-range thalamocortical connectivity indicates that functional thalamocortical input is not affected. Higher ALFF in the somatosensory cortex may indicate the developmental disruption of cortical neuronal circuits after neonatal anesthesia exposure, including excessive neuronal synchronization that may underlie the observed cognitive deficits.Visualizing neuronal activation on a brain-wide scale yet with cellular resolution is a fundamental technical challenge for neuroscience. This would enable analyzing how different neuronal circuits are disrupted in pathology and how they could be rescued by pharmacological treatments. Although this goal would have appeared visionary a decade ago, recent technological advances make it eventually feasible. Here, we review the latest developments in the fields of genetics, sample preparation, imaging, and image analysis that could be combined to afford whole-brain cell-resolution activation mapping. We show how the different biochemical and optical methods have been coupled to study neuronal circuits at different spatial and temporal scales, and with cell-type specificity. The inventory of techniques presented here could be useful to find the tools best suited for a specific experiment. We envision that in the next years, mapping of neuronal activation could become routine in many laboratories, allowing dissecting the neuronal counterpart of behavior.Parkinson's disease (PD) is characterized by motor dysfunctions including bradykinesia, tremor at rest and motor instability. These symptoms are associated with the progressive degeneration of dopaminergic neurons originating in the substantia nigra pars compacta and projecting to the corpus striatum, and by accumulation of cytoplasmic inclusions mainly consisting of aggregated alpha-synuclein, called Lewy bodies. PD is a complex, multifactorial disorder and its pathogenesis involves multiple pathways and mechanisms such as α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport, and neuroinflammation. Motor symptoms manifest when there is already an extensive dopamine denervation. There is therefore an urgent need for early biomarkers to apply disease-modifying therapeutic strategies. Visual defects and retinal abnormalities, including decreased visual acuity, abnormal spatial contrast sensitivity, color vision defects, or deficits in more complex visual taskies in the development of PD visual defects. We finally propose that the eye may be considered as a complementary experimental model to identify possible novel disease' pathways or to test novel therapeutic approaches for PD.The enzyme aromatase catalyzes the final step in estrogen biosynthesis, converting testosterone to estradiol, and is expressed in the brain of all mammals. Estrogens are thought to be important for maintenance of cognitive function in women, whereas testosterone is thought to modulate cognitive abilities in men. Here, we compare differences in cognitive performance in relation to brain aromatase availability in healthy men and women. Twenty-seven healthy participants were administered tests of verbal learning and memory and perceptual/abstract reasoning. In vivo images of brain aromatase availability were acquired in this sample using positron emission tomography (PET) with the validated aromatase radiotracer [11C]vorozole. Regions of interest were placed bilaterally on the amygdala and thalamus where aromatase availability is highest in the human brain. Though cognitive performance and aromatase availability did not differ as a function of sex, higher availability of aromatase in the amygdala was associated with lower cognitive performance in men.