Huntington disease (HD) is an autosomal dominant disorder in which degeneration of medium-sized spiny striatal neurons occurs. The HD gene and the protein it encodes, huntingtin, have been identified but their functions remain unknown. Transgenic mouse models for developed we examined responses recorded vitro to application N-methyl-D-aspartate (NMDA) two these. first model (R6/2) expresses exon 1 human with approximately 150 CAG repeats. In R6/2 enhancement currents induced by selective...

Dopamine (DA), via activation of D1 receptors, enhances N-methyl-d-aspartate (NMDA)-evoked responses in striatal neurons. The present investigation examined further the properties this enhancement and potential mechanisms by which might be effected. Dissociated medium-sized neurons were obtained from intact rats mice or mutant lacking DA cyclic adenosine 3′,5′ monophosphate (cAMP)-regulated phosphoprotein M R 32,000 (DARPP-32). NMDA (10–1,000 μM) induced inward currents all In acutely...

Dopamine (DA) receptors play an important role in the modulation of excitability and responsiveness neurons to activation excitatory amino acid striatum. In present study, we utilized mice with genetic deletion D 2 or 4 DA their wild-type (WT) controls examine if absence either receptor subtype affects striatal synaptic activity. Immunocytochemical analysis verified protein expression striatum receptor-deficient mutant animals. Sharp electrode current- whole cell patch voltage-clamp...

The mechanisms responsible for seizure generation in cortical dysplasia (CD) are unknown, but morphologically abnormal cells could contribute. We examined the passive and active membrane properties of from pediatric CD vitro. Normal- abnormal-appearing were identified by using infrared videomicroscopy biocytin slices children with mild to severe CD. Electrophysiological assessed patch clamp recordings. Four groups observed. first consisted large, pyramidal probably corresponding cytomegalic...

Dopamine is a critical determinant of neostriatal function, but its impact on intrastriatal GABAergic signaling poorly understood. The role D(1) dopamine receptors in the regulation postsynaptic GABA(A) was characterized using whole cell voltage-clamp recordings acutely isolated, rat medium spiny neurons. Exogenous application GABA evoked rapidly desensitizing current that blocked by bicuculline. Application receptor agonist SKF 81297 reduced GABA-evoked currents most antagonist SCH 23390...

The dopamine D(4) receptor (D(4)R) is predominantly expressed in the frontal cortex (FC), a brain region that receives dense input from midbrain (DA) neurons and associated with cognitive emotional processes. However, physiological significance of this subtype has been difficult to explore because slow development D(4)R agonists antagonists selectivity efficacy which have rigorously demonstrated vivo. We attempted overcome limitation by taking multidimensional approach characterization mice...

Huntington's disease (HD) is a neurodegenerative disorder that mainly affects the projection neurons of striatum and cerebral cortex. Genetic mouse models HD have shown susceptible to mutation exhibit morphological electrophysiological dysfunctions before during development behavioral phenotype. We used transgenic examine inwardly outwardly rectifying K+ conductances, as well expression some related channel subunits. Experiments were conducted in slices dissociated cells from two models,...

Seizures in cortical dysplasia (CD) could be from cytomegalic neurons and balloon cells acting as epileptic ‘pacemakers’, or abnormal neurotransmission. This study examined these hypotheses using vitro electrophysiological techniques to determine intrinsic membrane properties spontaneous glutamatergic GABAergic synaptic activity for normal-pyramidal neurons, 67 neocortical sites originating 43 CD patients (ages 0.2–14 years). Magnetic resonance imaging (MRI),...

Abstract We have studied the morphological changes of dendrites pyramidal neurons prefrontal cortex (PFC) and medium spiny caudate‐putamen (CPu) nucleus accumbens (NAcc) induced by injection 6‐hydroxydopamine (6‐OHDA) into substantia nigra pars compacta (SNc). The unilateral 6‐OHDA‐induced lesion SNc was made in Wistar rats to produce Parkinson model lesion. Two weeks after injection, testing rotational behavior caused amphetamine done assess animals with lesions. Four 6‐OHDA morphology...

Emerging evidence has implicated a potential role for 5-HT(4) receptors in cognition and anxiolysis. One of the main target structures on 'cognitive emotional' pathways is prefrontal cortex (PFC). As GABAergic signalling plays key regulating PFC functions, we examined effect GABA(A) receptor channels pyramidal neurons. Application agonists produced either an enhancement or reduction GABA-evoked currents neurons, which are both mediated by anchored protein kinase A (PKA). Although PKA...

Recent data suggest that diabetes is a risk factor for pulmonary hypertension. The aim of the present study was to analyze whether induces endothelial dysfunction in arteries and mechanisms involved. Male Sprague-Dawley rats were randomly divided into control (saline) diabetic group (70 mg/kg(-1) streptozotocin). After 6 wk, intrapulmonary mounted isometric tension recording, function tested by relaxant response acetylcholine. Protein expression localization measured Western blot...

Summary: Purpose : Cortical dysplasia (CD) is a common pathological substrate in patients with early‐onset childhood epilepsy. In CD tissue, little known about the mechanisms responsible for cellular hyperexcitability. this study, we report initial electrophysiological and morphological observations from normal dysmorphic cells pediatric patients. Methods Neocortical “most” “least” epileptogenic areas were sampled based on neuroimaging electrocorticography 15 (ages 0.3 to 14 years)....

The mechanisms by which glutamate shapes the activity of striatal medium spiny neurons are fundamental importance to our understanding normative and pathological physiology. Non-N-Methyl-<i>D</i>-aspartate (non-NMDA) receptor expression function were studied in with a combination single cell RT-PCR, immunocytochemistry whole-cell voltage-clamp techniques. Reverse transcription polymerase chain reaction analysis found that GluR2 mRNA appeared be most abundant widely distributed...

1. Synaptic potentials induced by 4-aminopyridine (4-AP) were recorded intracellularly from rat neostriatal neurons in an vitro slice preparation. EC50 for this 4-AP action was approximately 120 microM. The threshold activation of synaptic 5 2. 4-AP-induced appeared stochastically. Most blocked 1 microM tetrodotoxin or 400 Cd2+. Therefore they reflect a release neurotransmitters dependent on both Ca2+ entry to the terminals and potential firing. 3. Bicuculline (BIC) (< = 10 microM),...

Abstract Infrared videomicroscopy and differential interference contrast optics were used to identify medium‐ large‐sized neurons in striatal slices from young rats. Whole‐cell patch‐clamp recordings obtained compare membrane currents evoked by application of N ‐methyl‐ d ‐aspartate (NMDA) kainate. Inward current densities induced NMDA significantly smaller large‐ than medium‐sized neurons. The negative slope conductance for was greater more depolarization required remove the Mg 2+ blockade....

Recent epidemiological data suggest that diabetes is a risk factor for pulmonary arterial hypertension. The aim of the present study was to analyze link between type 1 and dysfunction in rats. Male Sprague-Dawley rats were randomly divided into control group (saline) diabetic (70 mg/kg streptozotocin). After 6 weeks, animals showed down-regulation lung bone morphogenetic protein receptor 2, up-regulation 5-hydroxytryptamine (5-HT) 2A receptors cyclooxygenase-2 (COX-2) proteins as measured by...

Nicotine is an addictive substance of tobacco. It has been suggested that nicotine acts on glutamatergic (N-methyl-d-aspartate, NMDA) neurotransmission affecting dopamine release in the mesocorticolimbic system. This effect reflected neuroadaptative changes can modulate prefrontal cortex (PFC) and nucleus accumbens (NAcc) core (cNAcc) shell (sNAcc) regions. We evaluated chronic administration (4.23 mg/kg/day for 14 days) NMDA activated currents dissociated neurons from PFC, NAcc (from...