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Scientific Reports Jun 2024Head-fixation of mice enables high-resolution monitoring of neuronal activity coupled with precise control of environmental stimuli. Virtual reality can be used to...
Head-fixation of mice enables high-resolution monitoring of neuronal activity coupled with precise control of environmental stimuli. Virtual reality can be used to emulate the visual experience of movement during head fixation, but a low inertia floating real-world environment (mobile homecage, MHC) has the potential to engage more sensory modalities and provide a richer experimental environment for complex behavioral tasks. However, it is not known whether mice react to this adapted environment in a similar manner to real environments, or whether the MHC can be used to implement validated, maze-based behavioral tasks. Here, we show that hippocampal place cell representations are intact in the MHC and that the system allows relatively long (20 min) whole-cell patch clamp recordings from dorsal CA1 pyramidal neurons, revealing sub-threshold membrane potential dynamics. Furthermore, mice learn the location of a liquid reward within an adapted T-maze guided by 2-dimensional spatial navigation cues and relearn the location when spatial contingencies are reversed. Bilateral infusions of scopolamine show that this learning is hippocampus-dependent and requires intact cholinergic signalling. Therefore, we characterize the MHC system as an experimental tool to study sub-threshold membrane potential dynamics that underpin complex navigation behaviors.
Topics: Animals; Mice; Spatial Navigation; Maze Learning; Male; Hippocampus; Pyramidal Cells; Mice, Inbred C57BL; Membrane Potentials; CA1 Region, Hippocampal; Virtual Reality; Scopolamine; Patch-Clamp Techniques
PubMed: 38906952
DOI: 10.1038/s41598-024-64807-w -
Science Advances Jun 2024The suprachiasmatic nucleus (SCN) sets the phase of oscillation throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the...
The suprachiasmatic nucleus (SCN) sets the phase of oscillation throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the organum vasculosum of the lamina terminalis (OVLT), begging the question of the direction of blood flow and the nature of diffusible signals that flow in this specialized vasculature. Using a combination of anatomical and in vivo two-photon imaging approaches, we unequivocally show that blood flows unidirectionally from the SCN to the OVLT, that blood flow rate displays daily oscillations with a higher rate at night than in the day, and that circulating vasopressin can access portal vessels. These findings highlight a previously unknown central nervous system communication pathway, which, like that of the pituitary portal system, could allow neurosecretions to reach nearby target sites in OVLT, avoiding dilution in the systemic blood. In both of these brain portal pathways, the target sites relay signals broadly to both the brain and the rest of the body.
Topics: Suprachiasmatic Nucleus; Animals; Mice; Hypothalamus; Brain; Portal System; Male; Vasopressins; Cerebrovascular Circulation; Circadian Rhythm
PubMed: 38905332
DOI: 10.1126/sciadv.adn8350 -
PloS One 2024Visual processing relies on the identification of both local and global features of visual stimuli. While well investigated at the behavioral level, the underlying brain...
Visual processing relies on the identification of both local and global features of visual stimuli. While well investigated at the behavioral level, the underlying brain mechanisms are less clear, especially in the context of aging. Using fMRI, we aimed to investigate the neural correlates underlying local and global processing in early and late adulthood. We recruited 77 healthy adults aged 19-77 who completed a visual search task based on 2-level hierarchical stimuli made of squares and/or circles. Participants were instructed to detect a target (a square) at either a local (small) or global (large) level of a hierarchical geometrical form, in the presence or absence of other hierarchical geometrical forms (distractors). At the behavioral level, we revealed high accuracy for all participants, but older participants were slower to detect local targets, specifically in presence of distractors. At the brain level, while both local and global processing were associated with occipital activation, local processing also recruited the anterior insula and dorsal anterior cingulate cortex, that are core regions of the salience network. However, while the presence of distractors in the local condition elicited specifically stronger activation within the right anterior insula for the young group, it was not observed for older participants. In addition, older participants showed less activation than younger participants in the occipital cortex, especially for the most complex conditions. Our findings suggest that the brain correlates underlying local and global processing change with aging, especially for complex visual patterns. These results are discussed in terms of top-down reduction effects from the salience network on primary visual areas, that may lead to specific difficulties to process local visual details in older adults.
Topics: Humans; Adult; Male; Female; Middle Aged; Magnetic Resonance Imaging; Aged; Young Adult; Brain Mapping; Visual Perception; Photic Stimulation; Brain; Aging; Reaction Time; Occipital Lobe
PubMed: 38905236
DOI: 10.1371/journal.pone.0303796 -
PloS One 2024Defining the brain mechanisms underlying initial emotional evaluation is a key but unexplored clue to understanding affective processing. Event-related potentials...
Defining the brain mechanisms underlying initial emotional evaluation is a key but unexplored clue to understanding affective processing. Event-related potentials (ERPs), especially suited for investigating this issue, were recorded in two experiments (n = 36 and n = 35). We presented emotionally negative (spiders) and neutral (wheels) silhouettes homogenized regarding their visual parameters. In Experiment 1, stimuli appeared at fixation or in the periphery (200 trials per condition and location), the former eliciting a N40 (39 milliseconds) and a P80 (or C1: 80 milliseconds) component, and the latter only a P80. In Experiment 2, stimuli were presented only at fixation (500 trials per condition). Again, an N40 (45 milliseconds) was observed, followed by a P100 (or P1: 105 milliseconds). Analyses revealed significantly greater N40-C1P1 peak-to-peak amplitudes for spiders in both experiments, and ANCOVAs showed that these effects were not explained by C1P1 alone, but that processes underlying N40 significantly contributed. Source analyses pointed to V1 as an N40 focus (more clearly in Experiment 2). Sources for C1P1 included V1 (P80) and V2/LOC (P80 and P100). These results and their timing point to low-order structures (such as visual thalamic nuclei or superior colliculi) or the visual cortex itself, as candidates for initial evaluation structures.
Topics: Humans; Emotions; Male; Female; Adult; Photic Stimulation; Young Adult; Electroencephalography; Evoked Potentials; Evoked Potentials, Visual; Visual Perception; Brain; Visual Cortex
PubMed: 38905211
DOI: 10.1371/journal.pone.0299677 -
Noise & HealthDue to the abnormal structure and function of brain neural networks in special populations, such as children, elderly individuals, and individuals with mental disorders,... (Review)
Review
Due to the abnormal structure and function of brain neural networks in special populations, such as children, elderly individuals, and individuals with mental disorders, noise exposure is more likely to have negative psychological and cognitive nonauditory effects on these individuals. There are unique and complex neural mechanisms underlying this phenomenon. For individuals with mental disorders, there are anomalies such as structural atrophy and decreased functional activation in brain regions involved in emotion and cognitive processing, such as the prefrontal cortex (PFC). Noise exposure can worsen these abnormalities in relevant brain regions, further damaging neural plasticity and disrupting normal connections and the transmission of information between the PFC and other brain areas by causing neurotransmitter imbalances. In the case of children, in a noisy environment, brain regions such as the left inferior frontal gyrus and PFC, which are involved in growth and development, are more susceptible to structural and functional changes, leading to neurodegenerative alterations. Furthermore, noise exposure can interrupt auditory processing neural pathways or impair inhibitory functions, thus hindering children's ability to map sound to meaning in neural processes. For elderly people, age-related shrinkage of brain regions such as the PFC, as well as deficiencies in hormone, neurotransmitter, and nutrient levels, weakens their ability to cope with noise. Currently, it is feasible to propose and apply coping strategies to improve the nonauditory effects of noise exposure on special populations based on the plasticity of the human brain.
Topics: Humans; Noise; Child; Brain; Aged; Neuronal Plasticity; Environmental Exposure; Prefrontal Cortex; Mental Disorders
PubMed: 38904804
DOI: 10.4103/nah.nah_78_23 -
ELife Jun 2024Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, the effects of MCS on neuronal hyperexcitability in AD are...
Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, the effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated the effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice are generalized EEG spikes (interictal spikes [IIS]). IIS also are common in other mouse models and occur in AD patients. In mouse models, hyperexcitability is also reflected by elevated expression of the transcription factor ∆FosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. Therefore, we studied ΔFosB expression in GCs. We also studied the neuronal marker NeuN within hilar neurons of the DG because reduced NeuN protein expression is a sign of oxidative stress or other pathology. This is potentially important because hilar neurons regulate GC excitability. Tg2576 breeding pairs received a diet with a relatively low, intermediate, or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ∆FosB expression was reduced, and hilar NeuN expression was restored. Using the novel object location task, spatial memory improved. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB protein expression. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB, and spatial memory in an animal model of AD.
Topics: Animals; Alzheimer Disease; Choline; Disease Models, Animal; Mice; Dietary Supplements; Female; Mice, Transgenic; Proto-Oncogene Proteins c-fos; Neurons; Male; Dentate Gyrus; Nerve Tissue Proteins; DNA-Binding Proteins
PubMed: 38904658
DOI: 10.7554/eLife.89889 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024The locus coeruleus-norepinephrine system plays a key role in supporting brain health along the lifespan, notably through its modulatory effects on neuroinflammation....
The locus coeruleus-norepinephrine system plays a key role in supporting brain health along the lifespan, notably through its modulatory effects on neuroinflammation. Using ultra-high field diffusion magnetic resonance imaging, we examined whether microstructural properties (neurite density index and orientation dispersion index) in the locus coeruleus were related to those in cortical and subcortical regions, and whether this was modulated by plasma glial fibrillary acidic protein levels, as a proxy of astrocyte reactivity. In our cohort of 60 healthy individuals (30 to 85 yr, 50% female), higher glial fibrillary acidic protein correlated with lower neurite density index in frontal cortical regions, the hippocampus, and the amygdala. Furthermore, under higher levels of glial fibrillary acidic protein (above ~ 150 pg/mL for cortical and ~ 145 pg/mL for subcortical regions), lower locus coeruleus orientation dispersion index was associated with lower orientation dispersion index in frontotemporal cortical regions and in subcortical regions. Interestingly, individuals with higher locus coeruleus orientation dispersion index exhibited higher orientation dispersion index in these (sub)cortical regions, despite having higher glial fibrillary acidic protein levels. Together, these results suggest that the interaction between locus coeruleus-norepinephrine cells and astrocytes can signal a detrimental or neuroprotective pathway for brain integrity and support the importance of maintaining locus coeruleus neuronal health in aging and in the prevention of age-related neurodegenerative diseases.
Topics: Humans; Female; Male; Locus Coeruleus; Astrocytes; Aged; Middle Aged; Adult; Aged, 80 and over; Glial Fibrillary Acidic Protein; Magnetic Resonance Imaging; Cerebral Cortex; Brain; Diffusion Magnetic Resonance Imaging; Neurites
PubMed: 38904081
DOI: 10.1093/cercor/bhae261 -
Biomedical Engineering Online Jun 2024The subjective sign of a serious pandemic in human work and life is mathematical neural tinnitus. fNIRS (functional near-infrared spectroscopy) is a new non-invasive...
BACKGROUND
The subjective sign of a serious pandemic in human work and life is mathematical neural tinnitus. fNIRS (functional near-infrared spectroscopy) is a new non-invasive brain imaging technology for studying the neurological activity of the human cerebral cortex. It is based on neural coupling effects. This research uses the fNIRS approach to detect differences in the neurological activity of the cerebral skin in the sound stimulation mission in order to better discriminate between the sensational neurological tinnitus.
METHODS
In the fNIRS brain imaging method, 14 sensorineural tinnitus sufferers and 14 healthy controls listened to varied noise and quiet for fNIRS data collection. Linear fitting was employed in MATLAB to eliminate slow drifts during preprocessing and event-related design analysis. The false discovery rate (FDR) procedure was applied in IBM SPSS Statistics 26.0 to control the false positive rate in multiple comparison analyses.
RESULTS
When the ill group and the healthy control group were stimulated by pink noise, there was a significant difference in blood oxygen concentration (P < 0.05), and the healthy control group exhibited a high activation, according to the fNIRS measurement data. The blood oxygen concentration level in the patient group was dramatically enhanced after one month of acupuncture therapy under the identical stimulation task settings, and it was favorably connected with the levels of THI and TEQ scales.
CONCLUSIONS
Using sensorineural tinnitus illness as an example, fNIRS technology has the potential to disclose future pathological study on subjective diseases throughout time. Other clinical disorders involving the temporal lobe and adjacent brain areas may also be examined, in addition to tinnitus-related brain alterations.
Topics: Humans; Tinnitus; Spectroscopy, Near-Infrared; Male; Temporal Lobe; Female; Adult; Acoustic Stimulation; Middle Aged; Oxygen; Case-Control Studies
PubMed: 38902700
DOI: 10.1186/s12938-024-01255-7 -
Scientific Reports Jun 2024Nicotinic acetylcholine receptors (nAChRs) in the medial habenula (MHb)-interpeduncular nucleus (IPN) pathway play critical roles in nicotine-related behaviors. This...
Nicotinic acetylcholine receptors (nAChRs) in the medial habenula (MHb)-interpeduncular nucleus (IPN) pathway play critical roles in nicotine-related behaviors. This pathway is particularly enriched in nAChR α3 and β4 subunits, both of which are genetically linked to nicotine dependence. However, the cellular and subcellular expression of endogenous α3β4-containing nAChRs remains largely unknown because specific antibodies and appropriate detection methods were unavailable. Here, we successfully uncovered the expression of endogenous nAChRs containing α3 and β4 subunits in the MHb-IPN pathway using novel specific antibodies and a fixative glyoxal that enables simultaneous detection of synaptic and extrasynaptic molecules. Immunofluorescence and immunoelectron microscopy revealed that both subunits were predominantly localized to the extrasynaptic cell surface of somatodendritic and axonal compartments of MHb neurons but not at their synaptic junctions. Immunolabeling for α3 and β4 subunits disappeared in α5β4-knockout brains, which we used as negative controls. The enriched and diffuse extrasynaptic expression along the MHb-IPN pathway suggests that α3β4-containing nAChRs may enhance the excitability of MHb neurons and neurotransmitter release from their presynaptic terminals in the IPN. The revealed distribution pattern provides a molecular and anatomical basis for understanding the functional role of α3β4-containing nAChRs in the crucial pathway of nicotine dependence.
Topics: Animals; Receptors, Nicotinic; Habenula; Interpeduncular Nucleus; Mice; Mice, Knockout; Neurons; Synapses; Mice, Inbred C57BL; Male
PubMed: 38902419
DOI: 10.1038/s41598-024-65076-3 -
Scientific Reports Jun 2024Glutamatergic neurotransmission and oxidative stress are involved in the pathophysiology of seizures. Some anticonvulsants exert their effects through modulation of...
Glutamatergic neurotransmission and oxidative stress are involved in the pathophysiology of seizures. Some anticonvulsants exert their effects through modulation of these pathways. Trigonelline (TRG) has been shown to possess various pharmacological effects like neuroprotection. Therefore, this study was performed to determine TRG's anticonvulsant effects, focusing on its potential effects on N-methyl-D-aspartate (NMDA) receptors, a type of glutamate receptor, and oxidative stress state in the prefrontal cortex (PFC) in PTZ-induced seizure in mice. Seventy-two male mice were randomly divided into nine groups. The groups included mice that received normal saline, TRG at doses of 10, 50, and 100 mg/kg, diazepam, NMDA (an agonist), ketamine (an antagonist), the effective dose of TRG with NMDA, as well as sub-effective dose of TRG with ketamine, respectively. All agents were administrated intraperitoneally 60 min before induction of seizures by PTZ. Latency to seizure, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels in serum and PFC were measured. Furthermore, the gene expression of NR2A and NR2B, subunits of NMDA receptors, was measured in the PFC. TRG administration increased the latency to seizure onset and enhanced TAC while reducing MDA levels in both the PFC and serum. TRG also decreased the gene expression of NR2B in the PFC. Unexpectedly, the findings revealed that the concurrent administration of ketamine amplified, whereas NMDA mitigated, the impact of TRG on latency to seizure. Furthermore, NMDA diminished the positive effects of TRG on antioxidant capacity and oxidative stress, while ketamine amplified these beneficial effects, indicating a complex interaction between TRG and NMDA receptor modulation. In the gene expression of NMDA receptors, results showed that ketamine significantly decreased the gene expression of NR2B when co-administrated with a sub-effective dose of TRG. It was found that, at least partially, the anticonvulsant effect of TRG in PTZ-induced seizures in male mice was mediated by the attenuation of glutamatergic neurotransmission as well as the reduction of oxidative stress.
Topics: Animals; Receptors, N-Methyl-D-Aspartate; Oxidative Stress; Anticonvulsants; Mice; Male; Alkaloids; Seizures; Prefrontal Cortex; Malondialdehyde; Ketamine; Pentylenetetrazole; Antioxidants
PubMed: 38902338
DOI: 10.1038/s41598-024-65301-z