In the present study, we used a mouse model of chronic intermittent ethanol (CIE) exposure to examine how CIE alters plasticity medial prefrontal cortex (mPFC). acute slices obtained either immediately or 1-week after last episode alcohol exposure, voltage-clamp recording excitatory post-synaptic currents (EPSCs) in mPFC layer V pyramidal neurons revealed that resulted an increase NMDA/AMPA current ratio. This appeared result from selective NMDA component EPSC. Consistent with this, Western...

The importance of dopamine (DA) for prefrontal cortical (PFC) cognitive functions is widely recognized, but its mechanisms action remain controversial. DA thought to increase signal gain in active networks according an inverted U dose-response curve, and these effects may depend on both tonic phasic release from midbrain ventral tegmental area (VTA) neurons.We used patch-clamp recordings organotypic co-cultures the PFC, hippocampus VTA study modulation spontaneous network activity form...

Fearful experiences can produce long-lasting and debilitating memories. Extinction of the fear response requires consolidation new memories that compete with fearful associations. Subjects posttraumatic stress disorder (PTSD) show impaired extinction conditioned fear, which is associated decreased ventromedial prefrontal cortex (vmPFC) control over amygdala activity. Vagus nerve stimulation (VNS) enhances memory in both rats humans, pairing VNS exposure to cues learning rats. Here we...

Abstract F1FO-ATP synthase is critical for mitochondrial functions. The deregulation of this enzyme results in dampened oxidative phosphorylation (OXPHOS) and activated permeability transition (mPT), defects which accompany Alzheimer’s disease (AD). However, the molecular mechanisms that connect dysfunction AD remain unclear. Here, we observe selective loss oligomycin sensitivity conferring protein (OSCP) subunit physical interaction OSCP with amyloid beta (Aβ) brains individuals an mouse...

Although attention-deficit/hyperactivity disorder (ADHD) is thought to be an inhibitory disorder, the question remains of how specific deficit in adults and whether it distinguishes ADHD from borderline personality (BPD), with which shares several clinical features, particularly impulsiveness.The study assessed various motor cognitive functions (inhibition prepotent, ongoing interfering responses) addition working memory adult patients without BPD, compared subjects BPD alone controls. In...

Cognitive functions supported by neurons in the prefrontal cortex (PFC) are disrupted acute and chronic exposure to alcohol, yet little is known about mechanisms that underlie these effects. In present study, vivo vitro electrophysiology was used determine effects of ethanol on neuronal firing network patterns persistent activity PFC neurons. vivo, (0.375-3.5 g/kg) dose-dependently reduced spike measured with multielectrode extracellular recording anesthetized rat. an coculture system...

Reconsolidation updating is a form of memory modification in which an existing can become destabilized upon retrieval and subsequently be modified via protein-synthesis-dependent reconsolidation. However, not all memories appear to destabilize thus are modifiable reconsolidation approaches the neurobiological basis for this remains poorly understood. Here, we report that auditory fear created with 10 tone-shock pairings resistant retrieval-dependent destabilization associated increase...

Chronic pain patients suffer from pain-related cognitive deficits, even when taking commonly prescribed analgesics. These deficits are likely related to maladaptive plasticity in the frontal cortex. We sought model mice with neuropathic examine morphological mPFC and assess effects of several therapeutics. used an attentional set-shifting task spared nerve injury (SNI) who received either a single intrathecal injection analgesic dose clonidine, 7 d 100 mg/kg gabapentin, or 200 metformin....

In the primate dorsolateral prefrontal cortex (DLPFC), density of excitatory synapses decreases by 40–50% during adolescence. Although such substantial circuit refinement might underlie adolescence-related maturation working memory performance, its functional significance remains poorly understood. The consequences synaptic pruning may depend on properties eliminated synapses. Are adolescence functionally immature, as is case early brain development? Or do maturation-independent features tag...

The N-methyl-D-aspartic acid (NMDA)-hypofunction theory of schizophrenia suggests that is associated with a loss NMDA receptors, specifically on corticolimbic parvalbumin (PV)-expressing GABAergic interneurons, leading to disinhibition pyramidal cells and cortical desynchronization. However, the presumed changes in glutamatergic inputs onto PV interneurons have not been tested directly. We treated mice NMDAR antagonist ketamine during second postnatal week investigated persistent cellular...

GHSR1α and DRD1 coactivation preserves the integrity of hippocampal synapses in Alzheimer’s disease.

Abstract Remote and minimally‐invasive modulation of biological systems with light has transformed modern biology neuroscience. However, absorption scattering significantly prevents penetration to deep brain regions. Herein, we describe the use gold‐coated mechanoresponsive nanovesicles, which consist liposomes made from artificial phospholipid Rad‐PC‐Rad as a tool for delivery bioactive molecules into tissue. Near‐infrared picosecond laser pulses activated gold‐coating on surface creating...

Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking contingencies between drug-associated cues delivery reward during extinction learning reduces rates relapse. Here we used vagus nerve stimulation (VNS) to induce targeted synaptic plasticity facilitate appetitive behaviors reduce Rats self-administered cocaine were given VNS extinction. Relapse drug-seeking was assessed a cued reinstatement session. We...

Alterations of the normal redox state can be found in all stages schizophrenia, suggesting a key role for oxidative stress etiology and maintenance disease. Pharmacological blockade NMDA receptors disrupt natural antioxidant defense systems induce schizophrenia-like behaviors animals healthy human subjects. Perinatal administration NMDAR antagonist ketamine produces persistent behavioral deficits adult mice which mimic range positive, negative, cognitive symptoms that characterize...

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide reinforcement that has been maintaining behavior. There is close correspondence between fear and human anxiety, therefore studies extinction learning might insight into biological nature anxiety-related disorders such as post-traumatic stress disorder, help develop strategies treat them. Preclinical research aims aid induce targeted plasticity in circuits consolidate newly...

Abstract Glutamate theories of schizophrenia suggest that the disease is associated with a loss NMDA receptors, specifically on GABAergic parvalbumin-expressing interneurons (PVIs), leading to changes in excitation–inhibition balance prefrontal cortex (PFC). Oxidative stress contributes PVI and development schizophrenia. Here, we investigated whether glutathione precursor N -acetyl cysteine (NAC) can prevent synaptic transmission at pyramidal cells PVIs result from developmental NMDAR...

Background The medial prefrontal cortex ( mPFC ) inhibits impulsive and compulsive behaviors that characterize drug abuse dependence. Acamprosate is the leading medication approved for maintenance of abstinence, shown to reduce craving relapse in animal models human alcoholics. Whether acamprosate can modulate executive functions are impaired by chronic ethanol (EtOH) exposure unknown. Here we explored effects on an attentional set‐shifting task tested whether these behavioral correlated...

Drugs of abuse cause changes in the prefrontal cortex (PFC) and associated regions that impair inhibitory control over drug-seeking. Breaking contingencies between drug-associated cues delivery reward during extinction learning reduces relapse. Vagus nerve stimulation (VNS) has previously been shown to enhance reduce Here we determined effects VNS-mediated release brain-derived neurotrophic factor (BDNF) on cue-induced reinstatement male rats trained self-administer cocaine. Pairing 10 d...

Dopaminergic regulation of primate dorsolateral prefrontal cortex (PFC) activity is essential for cognitive functions such as working memory. However, the cellular mechanisms dopamine neuromodulation in PFC are not well understood. We have studied effects receptor activation during persistent stimulation excitatory inputs onto fast-spiking GABAergic interneurons monkey PFC. Stimulation at 20 Hz induced short-term postsynaptic potential (EPSP) depression. The D1 agonist SKF81297 (5 μM)...

Vagus nerve stimulation (VNS) causes the release of several neuromodulators, leading to cortical activation and deactivation. The resulting preparatory plasticity can be used increase learning memory in both rats humans. effects VNS on cognition have mostly been studied either animal models different pathologies, and/or after extended VNS. Considerably less is known about acute Here, we examined short-term cognitive flexibility naïve rats, using three tasks that require comparatively brief...

Cognitive deficits in schizophrenia are linked to dysfunctions of the dorsolateral prefrontal cortex (DLPFC), including alterations parvalbumin (PV)-expressing interneurons (PVIs). Redox dysregulation and oxidative stress may represent convergence points pathology schizophrenia, causing dysfunction GABAergic loss PV. Here, we show that mitochondrial matrix protein cyclophilin D (CypD), a critical initiator permeability transition pore (mPTP) modulator intracellular redox state, is altered...