Mitigation of aging-related plasticity decline through taurine supplementation and environmental enrichment.

Aging-related biochemical changes in nerve cells lead to dysfunctional synapses and disrupted neuronal circuits, ultimately affecting vital processes such as brain plasticity, learning, and memory. The imbalance between excitation and inhibition in synaptic function during aging contributes to cognitive impairment, emphasizing the importance of compensatory mechanisms. Fear conditioning-related plasticity of the somatosensory barrel cortex, relying on the proper functioning and extensive up regulation of the GABAergic system, in particular interneurons containing somatostatin, is compromised in aging (one-year-old) mice.

Low-Affinity/High-Selectivity Dopamine Transport Inhibition Sufficient to Rescue Cognitive Functions in the Aging Rat.

The worldwide increase in cognitive decline, both in aging and with psychiatric disorders, warrants a search for pharmacological treatment. Although dopaminergic treatment approaches represent a major step forward, current dopamine transporter (DAT) inhibitors are not sufficiently specific as they also target other transporters and receptors, thus showing unwanted side effects. Herein, we describe an enantiomerically pure, highly specific DAT inhibitor, S-CE-123, synthetized in our laboratory.

Disrupted Functional Rich-Club Organization of the Brain Networks in Children with Attention-Deficit/Hyperactivity Disorder, a Resting-State EEG Study.

Growing evidence indicates that disruptions in the brain's functional connectivity play an important role in the pathophysiology of ADHD. The present study investigates alterations in resting-state EEG source connectivity and rich-club organization in children with inattentive (ADHD) and combined (ADHD) ADHD compared with typically developing children (TD) under the eyes-closed condition. EEG source analysis was performed by eLORETA in different frequency bands.

Resting state dynamic functional connectivity in children with attention deficit/hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is characterized by inattention, hyperactivity and impulsivity. In this study, we investigated group differences in dynamic functional connectivity (dFC) between 113 children with inattentive (46 ADHD) and combined (67 ADHD) ADHD and 76 typically developing (TD) children using resting-state functional MRI data. For dynamic connectivity analysis, the data were first decomposed into 100 independent components, among which 88 were classified into eight well-known resting-state networks (RSNs).

Reinstatement of synaptic plasticity in the aging brain through specific dopamine transporter inhibition.

Aging-related neurological deficits negatively impact mental health, productivity, and social interactions leading to a pronounced socioeconomic burden. Since declining brain dopamine signaling during aging is associated with the onset of neurological impairments, we produced a selective dopamine transporter (DAT) inhibitor to restore endogenous dopamine levels and improve cognitive function. We describe the synthesis and pharmacological profile of (S,S)-CE-158, a highly specific DAT inhibitor, which increases dopamine levels in brain regions associated with cognition.

Cortical source analysis of resting state EEG data in children with attention deficit hyperactivity disorder.

Objective: This study investigated age-dependent and subtype-related alterations in electroencephalography (EEG) power spectra and current source densities (CSD) in children with attention deficit and hyperactivity disorder (ADHD).

Methods: We performed spectral and cortical source (exact low-resolution electromagnetic tomography, eLORETA) analyses using resting state EEG recordings from 40 children (8-16 years) with combined and inattentive subtypes of ADHD and 41 age-matched healthy controls (HC). Group differences in EEG spectra and CSD were investigated at each scalp location, voxel and cortical region in delta, theta, alpha and beta bands.

The SLC6A3 gene polymorphism is related to the development of attentional functions but not to ADHD.

Neuropharmacological and human clinical studies have suggested that the brain dopaminergic system is substantively involved in normal and pathological phenotypes of attention. Dopamine transporter gene (SLC6A3) was proposed as a candidate gene for Attention-Deficit/Hyperactivity Disorder (ADHD). We investigated the effect of the SLC6A3 variants on cognitive performance in ADHD and healthy children and teenagers.

Differential effects of the mode of touch, active and passive, on experience-driven plasticity in the S1 cutaneous digit representation of adult macaque monkeys.

This study compared the receptive field (RF) properties and firing rates of neurons in the cutaneous hand representation of primary somatosensory cortex (areas 3b, 1, and 2) of 9 awake, adult macaques that were intensively trained in a texture discrimination task using active touch (fingertips scanned over the surfaces using a single voluntary movement), passive touch (surfaces displaced under the immobile fingertips), or both active and passive touch. Two control monkeys received passive exposure to the same textures in the context of a visual discrimination task. Training and recording extended over 1-2 yr per animal.

Attentional deficits and altered neuronal activation in medial prefrontal and posterior parietal cortices in mice with reduced dopamine transporter levels.

The executive control function of attention is regulated by the dopaminergic (DA) system. Dopamine transporter (DAT) likely plays a role in controlling the influence of DA on cognitive processes. We examined the effects of DAT depletion on cognitive processes related to attention.

Potential role of dopamine transporter in behavioral flexibility.

Behavioral flexibility is subserved by the prefrontal cortex and the basal ganglia. Orbitofrontal cortex (OFC) and dorsomedial striatum (DMS) form a functional frontocorticostriatal circuit crucial for the mediation of flexibility during reversal learning via dopamine (DA) neurotransmission. The regulatory control in maintaining DA homeostasis and function is provided by the dopamine transporter (DAT), which therefore likely plays a significant role in controlling the influence of DA on cognitive processes.

Age-Related Changes in Resting-State EEG Activity in Attention Deficit/Hyperactivity Disorder: A Cross-Sectional Study.

Numerous studies indicate that attention deficit/hyperactivity disorder (ADHD) is related to some developmental trends, as its symptoms change widely over time. Nevertheless, the etiology of this phenomenon remains ambiguous. There is a disagreement whether ADHD is related to deviations in brain development or to a delay in brain maturation.

Behavioral verification of associative learning in whiskers-related fear conditioning in mice.

Fear-conditioning is one of the most widely used paradigms in attempts to unravel the processes and mechanisms underlying learning and plasticity. In most of the Pavlovian conditioning paradigms auditory stimulus is used as a conditioned stimulus (CS), but conditioning can be accomplished also to tactile CS. The whisker-to-barrel tactile system in mice offers convenient way to investigate the brain pathways and mechanisms of learning, and plasticity of the brain cortex.

Interneurons containing somatostatin are affected by learning-induced cortical plasticity.

The maintenance of neural circuit stability is a dynamic process that requires the plasticity of many cellular and synaptic components. By changing the excitatory/inhibitory balance, inhibitory GABAergic plasticity can regulate excitability, and contribute to neural circuit function and refinement in learning and memory. Increased inhibitory GABAergic neurotransmission has been shown in brain structures involved in the learning process.

Correlated activation of the thalamocortical network in a simple learning paradigm.

The thalamocortical loop is a key player in sensory processing. We examined the functional interactions among its elements, expressed as cross-correlations between metabolic activity of the barrel cortex, somatosensory thalamic nuclei and posterior parietal cortex, in classical conditioning. In the training stimulation of vibrissae in mice was paired with a tail shock.

Matrix metalloproteinase inhibition counteracts impairment of cortical experience-dependent plasticity after photothrombotic stroke.

Matrix metalloproteinases (MMPs) are fine modulators of brain plasticity and pathophysiology. The inhibition of MMPs shortly after ischaemic stroke reduces the infarct size and has beneficial effects on post-stroke behavioural recovery. Our previous studies have shown that photothrombotic cortical stroke disrupts use-dependent plasticity in the neighbouring cortex.

A critical speed for gating of tactile detection during voluntary movement.

This study addressed the paradoxical observation that movement is essential for tactile exploration, and yet is accompanied by movement-related gating or suppression of tactile detection. Knowing that tactile gating covaries with the speed of movement (faster movements, more gating), we hypothesized that there would be no tactile gating at slower speeds of movement, corresponding to speeds commonly used during tactile exploration (<200 mm/s). Subjects (n = 21) detected the presence or absence of a weak electrical stimulus applied to the skin of the right middle finger during two conditions: rest and active elbow extension.

Involvement of retrosplenial cortex in classical conditioning.

The cingulate cortex, which comprises of two major subdivisions - anterior cingulate cortex (CG) and retrosplenial cortex (RSP), is implicated in many cognitive functions. The RSP is an important node in the systemic integration network. Studies point to its role in learning that involves spatial stimuli and navigation.

Rapid, learning-induced inhibitory synaptogenesis in murine barrel field.

The structure of neurons changes during development and in response to injury or alteration in sensory experience. Changes occur in the number, shape, and dimensions of dendritic spines together with their synapses. However, precise data on these changes in response to learning are sparse.

Brain activation patterns during classical conditioning with appetitive or aversive UCS.

The neural bases of appetitive and aversive conditioning are different, and at various stages of learning, may engage distinct cortical and subcortical networks. Using [14C]2-deoxyglucose (2-DG) autoradiography, we examined brain activation in mice during the first and the third sessions of a classical conditioning involving stimulation of whiskers on one side of the muzzle (conditioned stimulus, CS) paired with an aversive or appetitive unconditioned stimulus (UCS). The nucleus basalis magnocellularis showed stronger labelling during appetitive conditioning while the lateral hypothalamus was activated only during aversive pairing session.

Early-phase of learning enhances communication between brain hemispheres.

In the somatosensory system, inputs from one side of the body are only transmitted to the contralateral primary somatosensory cortex, but both sides of the body representation can interact via interhemispheric connections. These interactions depend on the behavioural requirements of the animal and its level of arousal. During the process of learning, alertness and attention may modify the responsiveness of neuronal pathways.

Deficits in experience-dependent cortical plasticity and sensory-discrimination learning in presymptomatic Huntington's disease mice.

Huntington's disease (HD) is one of a group of neurodegenerative diseases caused by an expanded trinucleotide (CAG) repeat coding for an extended polyglutamine tract. The disease is inherited in an autosomal dominant manner, with onset of motor, cognitive, and psychiatric symptoms typically occurring in midlife, followed by unremitting progression and eventual death. We report here that motor presymptomatic R6/1 HD mice show a severe impairment of somatosensory-discrimination learning ability in a behavioral task that depends heavily on the barrel cortex.

Impaired learning-dependent cortical plasticity in Huntington's disease transgenic mice.

Huntington's disease (HD) is a genetically transmitted neurodegenerative disorder. The neuropathology in HD is a selective neuronal cell death in several brain regions including cortex. Although changes in synaptic plasticity were shown within the hippocampus and striatum of HD transgenic mice, there are no studies considering neocortical synaptic plasticity abnormalities in HD.

Reduced plasticity of cortical whisker representation in adult tenascin-C-deficient mice after vibrissectomy.

The effect of the extracellular matrix recognition molecule tenascin-C on cerebral plasticity induced by vibrissectomy was investigated with 2-deoxyglucose (2DG) brain mapping in tenascin-C-deficient mice. Unilateral vibrissectomy sparing row C of vibrissae was performed in young adult mice. Two months later, cortical representations of spared row C vibrissae and control row C on the other side of the snout were visualized by [(14)C]2DG autoradiography.

Mice can learn roughness discrimination with vibrissae in a jump stand apparatus.

An adaptation of roughness discrimination task successfully used on rats was performed on mice. It was found that mice can master discrimination of rough surfaces using only mystacial vibrissae. This task can be used for studying sensory abilities of genetically modified mice as well as dynamics and pharmacology of complex sensory learning.