Local electrophysiology and microstimulation reveal site-specific neural activity and physiological effects but do not directly link these local effects to whole-brain responses from the same target site. We developed an MRI-compatible electrode implantation system for macaques that enables CT/MRI-based localization, postoperative depth adjustment, neural recording, microstimulation during behavioral testing, and subsequent electrical microstimulation combined with functional MRI (EM-fMRI) using the same implanted electrode. The system supported local field potential recording, a stimulation-induced reduction in pupil size, and distributed stimulation-evoked blood oxygenation level-dependent (BOLD) responses. This approach provides a practical framework for linking local neural activity and stimulation-induced physiological responses with whole-brain responses at the same target site.
Vocal learning requires juveniles to form auditory representations of adult vocal models that guide vocal practice. The caudomedial nidopallium (NCM), a higher-order auditory pallial region in songbirds, has been implicated in tutor-song memory and receives dopaminergic input, but whether dopamine receptor activation biases the emergence of song-specific selectivity during development remains unclear. We recorded NCM single-unit activity in juvenile male zebra finches with limited tutor-song exposure. One adult song was repeatedly presented after systemic administration of the D1-like receptor agonist SKF-38393, the D2-like receptor agonist quinpirole, or saline, and neural selectivity was assessed before and after pairing. Pairing did not produce a uniform population-wide shift in average selectivity. However, a linear mixed-effects model accounting for pre-pairing selectivity and multiple units per bird revealed significantly higher post-pairing selectivity in SKF-treated units than in saline-treated units. SKF-treated units also differed from quinpirole-treated units, whereas quinpirole and saline did not differ. Among initially non-selective units, threshold-defined gains occurred in 31.3% of SKF, 15.4% of saline, and 10.8% of quinpirole units, with SKF showing the highest gained fraction across all tested thresholds. Although the exact bird-label permutation test was not significant, continuous and threshold-based analyses provided convergent unit-level evidence for an SKF-associated enhancement of paired-song selectivity. These findings support neuromodulatory gating as a potential mechanism by which developmental auditory experience shapes stimulus-specific sensory representations.
Astrocytes are emerging in the neuroscience field as crucial modulators of brain functions, from the molecular control of synaptic plasticity to orchestrating brain-wide circuit activity for cognitive processes. The cellular pathways through which astrocytes modulate neuronal activity and plasticity are quite diverse. In this review, we focus on neurotrophic pathways, mostly those mediated by brain-derived neurotrophic factor (BDNF). Neurotrophins are a well-known family of trophic factors with pleiotropic functions in neuronal survival, maturation and activity. Within the brain, BDNF is the most abundantly expressed and most studied of all neurotrophins. While we have detailed knowledge of the effect of BDNF on neurons, much less is known about its physiology on astroglia. However, over the last years new findings emerged demonstrating that astrocytes take an active part into BDNF physiology. In this work, we discuss the state-of-the-art knowledge about astrocytes and BDNF. Indeed, astrocytes sense extracellular BDNF through its specific TrkB receptors and activate intracellular responses that greatly vary depending on the brain area, stage of development and receptors expressed. Astrocytes also uptake and recycle BDNF / proBDNF at synapses contributing to synaptic plasticity. Finally, experimental evidence is now available describing deficits in astrocytic BDNF in several neuropathologies, suggesting that astrocytic BDNF may represent a promising target for clinical translation.
The objective of study was to explore those brain areas that were affected at each stage during the progression of Alzheimer’s disease (AD). Six affected brain areas were explored at mild cognitive impairment, four at first stage and six at each of second and third stage of Alzheimer’s disease. The common brain regions among these stages were cuneus, precuneus, calcarine cortex, middle frontal gyrus, superior frontal gyrus, and frontal superior medial gyrus. The fMRI data at the resting state of 18 AD patients who were converted from MCI to stage 3 of Alzheimer's were taken from ADNI public source database. Among these patients, there were ten males and eight females. Independent component analysis was used to explore affected brain regions and an algorithm based on deep learning convolutional neural network was proposed for binary classification among the stages of Alzheimer’s disease. The proposed CNN model delivered 94.6 % accuracy for separating stage 1 of Alzheimer's disease from mild cognitive impairment. 96.7 % accuracy was acquired to distinguish stage 2 of Alzheimer's disease from mild cognitive impairment, and stage 3 of Alzheimer's disease was separated from mild cognitive impairment with an accuracy of 97.8 %.
Gabapentinoids are used worldwide as first-line agents for the treatment of neuropathic pain. Accumulating evidence indicates that one of the antihyperalgesic mechanisms of gabapentinoids is through activation of the noradrenergic pathway of the descending pain inhibition system. However, the involvement of the serotonin pathway is unclear. We investigated the effects of gabapentin (GBP) on the serotonergic pathway of the descending inhibitory system using the spinal nerve ligation (SNL) rat model. As in previous reports, administration of GBP to SNL rats improved paw withdrawal thresholds (PWT). Intrathecally administered serotonin receptor antagonists abolished GBP's amelioration in PWT. GBP did not ameliorate PWT in noradrenaline-depleted SNL rats by DSP-4. However, GBP ameliorated PWT in serotonin-depleted SNL rats by para-chlorophenylalanine, which was not inhibited by intrathecal administration of a serotonin receptor antagonist. Immunohistochemical analysis of serotonin in the spinal dorsal horn revealed a slight, albeit statistically insignificant, increase in 5-HT levels in SNL rats compared to naive rats. However, no apparent changes were observed before or after GBP administration in naive and SNL rats. In conclusion, the involvement of the serotonergic pathway in the antihyperalgesic effects of GBP on the spinal cord is secondary, although it cooperates with the noradrenergic system to produce analgesia.
