Automatic Experimental Numerosity Generation and Numerical Training for Rodents.

Non-symbolic stimuli representing numerosities are invariably associated with continuous magnitudes, complicating the interpretation of experimental studies on numerosity perception. Although various algorithms for experimental numerosity generation have been proposed, they do not consider the quantifiable distribution of values of continuous magnitudes and the degree of numerosity-magnitudes association. Consequently, they cannot thoroughly exclude the possibility of magnitudes integration or strategy switch between different magnitudes in numerical stimulus perception.

Distinct populations of lateral preoptic nucleus neurons jointly contribute to depressive-like behaviors through divergent projections in male mice.

The lateral preoptic area (LPO) is a component of the hypothalamus involved in various physiological functions including sleep-wakefulness transition, thermoregulation, and water-salt balance. In this study, we discovered that distinct LPO excitatory neurons project separately to the aversive processing center lateral habenula (LHb) and the reward processing hub ventral tegmental area (VTA). Following chronic restraint stress (CRS), the LHb-projecting and VTA-projecting LPO neurons exhibited increased and decreased neuronal activities, respectively.

Suppression of excitatory synaptic transmission in the centrolateral amygdala via presynaptic histamine H3 heteroreceptors.

The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons.

Disparate processing of numerosity and associated continuous magnitudes in rats.

The studies of number sense in different species are severely hampered by the inevitable entanglement of non-numerical attributes inherent in nonsymbolic stimuli representing numerosity, resulting in contrasting theories of numerosity processing. Here, we developed an algorithm and associated analytical methods to generate stimuli that not only minimized the impact of non-numerical magnitudes in numerosity perception but also allowed their quantification. We trained number-naïve rats with these stimuli as sound pulses representing two or three numbers and demonstrated that their numerical discrimination ability mainly relied on numerosity.

HMGB1 Mediates Inflammation-Induced DMT1 Increase and Dopaminergic Neurodegeneration in the Early Stage of Parkinsonism.

Both neuroinflammation and iron accumulation play roles in the pathogenesis of Parkinson's disease (PD). However, whether inflammation induces iron dyshomeostasis in dopaminergic neurons at an early stage of PD, at which no quantifiable dopaminergic neuron loss can be observed, is still unknown. As for the inflammation mediators, although several cytokines have been reported to increase in PD, the functions of these cytokines in the SN are double-edged and controversial.

Pharmacological interventions targeting α-synuclein aggregation triggered REM sleep behavior disorder and early development of Parkinson's disease.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by elevated motor behaviors and dream enactments in REM sleep, often preceding the diagnosis of Parkinson's disease (PD). As RBD could serve as a biomarker for early PD developments, pharmacological interventions targeting α-synuclein aggregation triggered RBD could be applied toward early PD progression. However, robust therapeutic guidelines toward PD-induced RBD are lacking, owing in part to a historical paucity of effective treatments and trials.

Edge-based network analysis reveals frequency-specific network dynamics in aberrant anxiogenic processing in rats.

Uncovering interactions between edges of brain networks can reveal the organizational principle of the networks and also their dysregulations underlying aberrant behaviours such as in neuropsychiatric diseases. In this study, we looked into the applicability of edge-based network analysis in uncovering possible network mechanisms of aberrant anxiogenic processing. Utilizing a rat model of prodromal Parkinson's disease we examined how a dorsomedial striatum-tied associative network (DSAN) may mediate context-based anxiogenic behaviour.

Input-timing-dependent plasticity at incoming synapses of the mushroom body facilitates olfactory learning in Drosophila.

Aversive olfactory conditioning in Drosophila is a valuable model for elucidating the mechanism of associative learning. Much effort has centered around the role of neuroplasticity at the mushroom body (MB)-mushroom body output neuron (MBON) synapses in mapping odors to specific behaviors. By electrophysiological recordings from MB neurons, we discovered a form of input-timing-dependent plasticity at the incoming synapses from projection neurons that controls the efficacy of aversive olfactory memory formation.

Secretin receptor deletion in the subfornical organ attenuates the activation of excitatory neurons under dehydration.

In mammals, thirst is strongly influenced by the subfornical organ (SFO), a forebrain structure that integrates circulating signals including osmotic pressure and sodium contents. Secretin (SCT), a classical gastrointestinal hormone, has been implicated as a humoral factor regulating body-fluid homeostasis. However, the neural mechanism of secretin in the central nervous system in managing thirst remains unclear.

The Role of Iron in Atherosclerosis in Apolipoprotein E Deficient Mice.

The role of iron in atherosclerosis is still a controversial and unsolved issue. Here, we investigated serum iron, expression of iron regulatory, transport and storage proteins, pro-inflammatory chemokines and cytokines in ApoE mice. We demonstrated that ApoE induced atherosclerosis and an increase in iron contents, expression of transferrin receptor 1 (TfR1), iron regulatory proteins (IRPs), heme oxygenase 1 (HO1), cellular adhesion molecules and pro-inflammatory cytokines, production of reactive oxygen species (ROS), and a reduction in expression of superoxide dismutase and glutathione peroxidase enzyme in aortic tissues.

Variational dimensions of cingulate cortex functional connectivity and implications in neuropsychiatric disorders.

Significant variations in brain functional connectivity exist in the healthy population, rendering the identification and characterization of their abnormalities in neuropsychiatric disorders difficult. Here, we proposed a new principal component analysis (PCA) approach to study variations in functional connectivity, focusing on major hubs of the salience network and default mode network, namely the anterior and posterior cingulate cortices. We analyzed the intersubject variability of human functional magnetic resonance imaging connectivity obtained from healthy, autistic, and schizophrenic subjects.

Chronic Intermittent Hypoxia-Induced Aberrant Neural Activities in the Hippocampus of Male Rats Revealed by Long-Term Recording.

Chronic intermittent hypoxia (CIH) occurs in obstructive sleep apnea (OSA), a common sleep-disordered breathing associated with malfunctions in multiple organs including the brain. How OSA-associated CIH impacts on brain activities and functions leading to neurocognitive impairment is virtually unknown. Here, by means of electrophysiological recordings via chronically implanted multi-electrode arrays in male rat model of OSA, we found that both putative pyramidal neurons and putative interneurons in the hippocampal CA1 subfield were hyper-excitable during the first week of CIH treatment and followed by progressive suppression of neural firing in the longer term.

Long-range monosynaptic inputs targeting apical and basal dendrites of primary motor cortex deep output neurons.

The primary motor cortex (M1) integrates various long-range signals from other brain regions for the learning and execution of goal-directed movements. How the different inputs target the distinct apical and basal dendrites of M1 pyramidal neurons is crucial in understanding the functions of M1, but the detailed connectivity pattern is still largely unknown. Here, by combining cre-dependent rabies virus tracing, layer-specific chemical retrograde tracing, optogenetic stimulation, and electrophysiological recording, we mapped all long-range monosynaptic inputs to M1 deep output neurons in layer 5 (L5) in mice.

Progressive Pontine-Medullary Dysfunction Leads to REM Sleep Behavior Disorder Symptoms in a Chronic Model of Parkinson's Disease.

Background: Clinical observations reveal that rapid eye movement (REM) sleep behavior disorder (RBD) often develops prior to alpha-synucleinopathies including Parkinson's disease (PD). However, a causal relationship between alpha-synucleinopathy and Parkinsonian neurodegeneration has not been delineated.

Methods: Rats were chronically treated with rotenone and EEG and EMG signals were recorded for analysis of sleep behavior, assisted by video recording of body movements.

Multifunctional Nanoprobe for the Delivery of Therapeutic siRNA and Real-Time Molecular Imaging of Parkinson's Disease Biomarkers.

Parkinson's disease (PD) has been recently associated with the excessive expression of matrix metalloproteinase 3 (MMP3). One of the major challenges in treating PD is to effectively detect and inhibit the early MMP3 activities to relieve the neural stress and inflammation responses. Previously, numerous upconversion nanoparticle (UCNP)-based nanoprobes have been designed for the detection of biomarkers in neurodegenerative diseases.

Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice.

Association of both iron/hepcidin and apolipoprotein E (ApoE) with development of Alzheimer disease (AD) and atherosclerosis led us to hypothesize that ApoE might be required for body iron homeostasis. Here, we demonstrated that ApoE knock-out (KO) induced a progressive accumulation of iron with age in the liver and spleen of mice. Subsequent investigations showed that the increased iron in the liver and spleen was due to phosphorylated extracellular regulated protein kinases (pERK) mediated up-regulation of transferrin receptor 1 (TfR1), and nuclear factor erythroid 2-related factor-2 (Nrf2)-dependent down-regulation of ferroportin 1.

The involvement of nuclear factor-κB in astroprotection against ischemia-reperfusion injury by ischemia-preconditioned neurons.

Ischemic preconditioned (IP) neurons protect astrocytes against ischemia/reperfusion (I/R)-induced injury by inhibiting oxidative stress. However, the relevant mechanisms are unknown. Based on the role of nuclear factor-κB (NF-κB) in cell survival and adaption to oxidative stress, we hypothesized that NF-κB might be associated with astroprotection induced by IP neurons via upregulation of antioxidant enzymes.

Randomized cortical stimulation could ameliorate locomotive inability in Parkinsonian rats: a pilot study.

Objective: Parkinson's disease (PD) is a neurodegenerative disease for which there is no known cure. Deep brain stimulation (DBS) is a surgical treatment effective in reducing motor symptoms for PD patients. Previous work implicates DBS may directly influence motor cortex through stochastic antidromic spikes originating from the site of stimulation.

Therapeutic effect of a histone demethylase inhibitor in Parkinson's disease.

Iron accumulation in the substantia nigra is recognized as a hallmark of Parkinson's disease (PD). Therefore, reducing accumulated iron and associated oxidative stress is considered a promising therapeutic strategy for PD. However, current iron chelators have poor membrane permeability and lack cell-type specificity.

Hepcidin attenuates the iron-mediated secondary neuronal injury after intracerebral hemorrhage in rats.

Iron plays a key role in secondary neuronal injury after intracerebral hemorrhage (ICH), and hepcidin is able to reduce brain iron in iron-overloaded rats by down-regulating iron transport proteins including ferroportin 1 and transferrin receptor 1. These led us to hypothesize that hepcidin might reduce iron-mediated neurotoxicity by inhibiting iron accumulation in ICH brain. Here, we examined effects of Ad-hepcidin (hepcidin expression adenovirus) on the nonheme iron contents, expression of hepcidin, ferritin and iron transport proteins, neuronal cell survival, water contents in the brain and/or cerebrospinal fluid (CSF), and ICH-induced apoptosis, neurological deficit by RT-PCR, Western blot analysis, NeuN Immunofluorescence, TUNEL, Fluoro-Jade B staining, behavioral performance and Morris water-maze tests in 510 rats.

Fully Affine Invariant Methods for Cross-Session Registration of Calcium Imaging Data.

two-photon microscopy permits simultaneous recording of the activity of the same neuronal population across multiple sessions in days or weeks, which is crucial for addressing many fundamental questions of neuroscience. The field-of-view (FOV) alignment is a necessary step for identifying the same neurons across multiple imaging sessions. Accurate FOV alignment becomes challenging in the situations of image blurring, insufficient common neurons, or uneven background brightness.

Brain Hepcidin Suppresses Major Pathologies in Experimental Parkinsonism.

Despite intensive research on Parkinson disease (PD) for decades, this common neurodegenerative disease remains incurable. We hypothesize that abnormal iron accumulation is a common thread underlying the emergence of the hallmarks of PD, namely mitochondrial dysfunction and α-synuclein accumulation. We investigated the powerful action of the main iron regulator hepcidin in the brain.