Sildenafil prevents right ventricular hypertrophy and improves heart rate variability in rats with pulmonary hypertension secondary to experimental diabetes.

Unlabelled: Chronic treatment with sildenafil (SILD) is an effective protector on the development of cardiovascular complications of pulmonary hypertension (PH) and diabetes. However, to date, no studies have evaluated the effect of SILD on cardiopulmonary pathophysiology during PH secondary to type 1 diabetes.

Aim: The present study aimed to evaluate the beneficial effects of chronic SILD treatment on pulmonary arterial pressure, right ventricular hypertrophy (RVH) and cardiac autonomic dysfunction in rats with PH secondary to diabetes.

Computational Molecular Characterization of the Interaction of Acetylcholine and the NMDA Receptor to Explain the Direct Glycine-Competitive Potentiation of NMDA-Mediated Neuronal Currents.

The activation of -methyl-d-aspartate receptor (NMDAR) is triggered by the closure of bilobed (D1 and D2) clamshell-like clefts upon binding glycine (Gly) and glutamate. There is evidence that cholinergic compounds modulate NMDAR-mediated currents via direct receptor-ligand interactions; however, molecular bases are unknown. Here, we first propose a mechanistic structure-based explanation for the observed ACh-induced submaximal potentiation of NMDA-elicited currents in striatal neurons by predicting competitive inhibition with Gly.

Noisy Light Augments the Na Current in Somatosensory Pyramidal Neurons of Optogenetic Transgenic Mice.

In previous reports, we developed a method to apply Brownian optogenetic noise-photostimulation (BONP, 470 nm) up to 0.67 mW on the barrel cortex of ChR2 transgenic mice. In such studies, we found that the BONP produces an increase in the evoked field potentials and the neuronal responses of pyramidal neurons induced by somatosensory mechanical stimulation.

Effects of Short-Term Random Noise Electrical Stimulation on Dissociated Pyramidal Neurons from the Cerebral Cortex.

Transcranial random noise electrical stimulation (tRNS) of the human brain is a non-invasive technique that can be employed to increase the excitability of the cerebral cortex; however, the physiological mechanisms remain unclear. Here we report for the first time the effects of short-term (250 ms) random noise electrical stimulation (RNS) on in-vitro acutely-isolated brain pyramidal neurons from the somatosensory and auditory cerebral cortex. We analyzed the correlation between the peak amplitude of the Na current and its latency for different levels of RNS.

Convergent evidence from alcohol-dependent humans and rats for a hyperdopaminergic state in protracted abstinence.

A major hypothesis in addiction research is that alcohol induces neuroadaptations in the mesolimbic dopamine (DA) system and that these neuroadaptations represent a key neurochemical event in compulsive drug use and relapse. Whether these neuroadaptations lead to a hypo- or hyperdopaminergic state during abstinence is a long-standing, unresolved debate among addiction researchers. The answer is of critical importance for understanding the neurobiological mechanism of addictive behavior.

Activation of 5-HT receptors inhibits GABAergic transmission by pre-and post-synaptic mechanisms in layer II/III of the juvenile rat auditory cortex.

The specific mechanisms by which serotonin (5-HT) modulates synaptic transmission in the auditory cortex are still unknown. In this work, we used whole-cell recordings from layer II/III of pyramidal neurons in rat brain slices to characterize the influence of 5-HT on inhibitory synaptic activity in the auditory cortex after pharmacological blockade of excitatory glutamatergic transmission. We found that bath application of 5-HT (5 µM) reduced the frequency and amplitude of both spontaneous and miniature inhibitory postsynaptic currents (IPSCs), reduced the amplitude of evoked IPSCs, and enhanced facilitation of paired pulse ratio (PPR), suggesting presynaptic inhibition.

Cholinergic direct inhibition of N-methyl-D aspartate receptor-mediated currents in the rat neocortex.

Acetylcholine (ACh) and N-methyl-D aspartate receptors (NMDARs) interact in the regulation of multiple important brain functions. NMDAR activation is indirectly modulated by ACh through the activation of muscarinic or nicotinic receptors. Scant information is available on whether ACh directly interacts with the NMDAR.