Different encoding of reward location in dorsal and intermediate hippocampus.

Hippocampal place cells fire at specific locations in the environment. They form a cognitive map that encodes spatial relations in the environment, including reward locations. As part of this encoding, dorsal CA1 (dCA1) place cells accumulate at reward.

Thalamus mediates neocortical Down state transition via GABA-receptor-targeting interneurons.

Slow-wave sleep is characterized by near-synchronous alternation of active Up states and quiescent Down states in the neocortex. Although the cortex itself can maintain these oscillations, the full expression of Up-Down states requires intact thalamocortical circuits. Sensory thalamic input can drive the cortex into an Up state.

The functional role of sequentially neuromodulated synaptic plasticity in behavioural learning.

To survive, animals have to quickly modify their behaviour when the reward changes. The internal representations responsible for this are updated through synaptic weight changes, mediated by certain neuromodulators conveying feedback from the environment. In previous experiments, we discovered a form of hippocampal Spike-Timing-Dependent-Plasticity (STDP) that is sequentially modulated by acetylcholine and dopamine.

Impaired spatial learning and suppression of sharp wave ripples by cholinergic activation at the goal location.

The hippocampus plays a central role in long-term memory formation, and different hippocampal network states are thought to have different functions in this process. These network states are controlled by neuromodulatory inputs, including the cholinergic input from the medial septum. Here, we used optogenetic stimulation of septal cholinergic neurons to understand how cholinergic activity affects different stages of spatial memory formation in a reward-based navigation task in mice.

Cholinergic modulation of Up-Down states in the mouse medial entorhinal cortex in vitro.

Cholinergic tone is high during wake and rapid eye movement sleep and lower during slow wave sleep (SWS). Nevertheless, the low tone of acetylcholine during SWS modulates sharp wave ripple incidence in the hippocampus and slow wave activity in the neocortex. Linking the hippocampus and neocortex, the medial entorhinal cortex (mEC) regulates the coupling between these structures during SWS, alternating between silent Down states and active Up states, which outlast neocortical ones.

Pharmacokinetics and Metabolism of Liposome-Encapsulated 2,4,6-Trihydroxygeranylacetophenone in Rats Using High-Resolution Orbitrap Liquid Chromatography Mass Spectrometry.

2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is a bioactive compound that shows excellent anti-inflammatory properties. However, its pharmacokinetics and metabolism have yet to be evaluated. In this study, a sensitive LC-HRMS method was developed and validated to quantify tHGA in rat plasma.

Partial restoration of physiological UP-state activity by GABA pathway modulation in an acute brain slice model of epilepsy.

In addition to reducing seizures, anti-epileptic treatments should preserve physiological network activity. Here, we used a thalamocortical slice preparation displaying physiological slow oscillations to investigate the effects of anticonvulsant drugs on physiological activity and epileptiform activity in two pharmacological epilepsy models. Thus, we compared the effects of GABA pharmacology on spontaneous physiological and pathological events in slices of the mouse barrel cortex.

A retrospective study on atrial fibrillation after coronary artery bypass grafting surgery at The National Heart Institute, Kuala Lumpur.

Atrial fibrillation (AF) is common after cardiac surgery and has been associated with poor outcome and increased resource utilization. The main objective of this study is to determine the incidence of POAF in Malaysia and identify the predictors of developing POAF. The secondary outcome of this study would be to investigate the difference in mortality and morbidity rates and the duration of intensive care unit (ICU), high dependency unit (HDU) and hospital stay between the two.

Basal Forebrain and Brainstem Cholinergic Neurons Differentially Impact Amygdala Circuits and Learning-Related Behavior.

The central cholinergic system and the amygdala are important for motivation and mnemonic processes. Different cholinergic populations innervate the amygdala, but it is unclear how these projections impact amygdala processes. Using optogenetic circuit-mapping strategies in choline acetyltransferase (ChAT)-cre mice, we demonstrate that amygdala-projecting basal forebrain and brainstem ChAT-containing neurons can differentially affect amygdala circuits and behavior.

Target Interneuron Preference in Thalamocortical Pathways Determines the Temporal Structure of Cortical Responses.

Sensory processing relies on fast detection of changes in environment, as well as integration of contextual cues over time. The mechanisms by which local circuits of the cerebral cortex simultaneously perform these opposite processes remain obscure. Thalamic "specific" nuclei relay sensory information, whereas "nonspecific" nuclei convey information on the environmental and behavioral contexts.

Comparison of three gamma oscillations in the mouse entorhinal-hippocampal system.

The entorhinal-hippocampal system is an important circuit in the brain, essential for certain cognitive tasks such as memory and navigation. Different gamma oscillations occur in this circuit, with the medial entorhinal cortex (mEC), CA3 and CA1 all generating gamma oscillations with different properties. These three gamma oscillations converge within CA1, where much work has gone into trying to isolate them from each other.

GluD1, linked to schizophrenia, controls the burst firing of dopamine neurons.

Human mutations of the GRID1 gene encoding the orphan delta1 glutamate receptor-channel (GluD1) are associated with schizophrenia but the explicit role of GluD1 in brain circuits is unknown. Based on the known function of its paralog GluD2 in cerebellum, we searched for a role of GluD1 in slow glutamatergic transmission mediated by metabotropic receptor mGlu1 in midbrain dopamine neurons, whose dysfunction is a hallmark of schizophrenia. We found that an mGlu1 agonist elicits a slow depolarizing current in HEK cells co-expressing mGlu1 and GluD1, but not in cells expressing mGlu1 or GluD1 alone.

Accumbal Cholinergic Interneurons Differentially Influence Motivation Related to Satiety Signaling.

Satiety, rather than all or none, can instead be viewed as a cumulative decrease in the drive to eat that develops over the course of a meal. The nucleus accumbens (NAc) is known to play a critical role in this type of value reappraisal, but the underlying circuits that influence such processes are unclear. Although NAc cholinergic interneurons (CINs) comprise only a small proportion of NAc neurons, their local impact on reward-based processes provides a candidate cell population for investigating the neural underpinnings of satiety.

Nicotinic Transmission onto Layer 6 Cortical Neurons Relies on Synaptic Activation of Non-α7 Receptors.

Nicotinic excitation in neocortex is mediated by low-affinity α7 receptors and by high-affinity α4β2 receptors. There is evidence that α7 receptors are synaptic, but it is unclear whether high-affinity receptors are activated by volume transmission or synaptic transmission. To address this issue, we characterized responses of excitatory layer 6 (L6) neurons to optogenetic release of acetylcholine (ACh) in cortical slices.

Study of comparative bioavailability of omeprazole pellets.

The objective of this study was to assess the bioequivalence between the omeprazole laboratory based formulation and the commercial formulation, Zimor Rubio, Spain, considered as reference formulation. The experiment was carried out according to a 2-period, 2-sequence crossover design with a two week washout period. A validated high performance liquid chromatographic method was applied for in vivo experiments.

Orexin-dependent activation of layer VIb enhances cortical network activity and integration of non-specific thalamocortical inputs.

Neocortical layer VI is critically involved in thalamocortical activity changes during the sleep/wake cycle. It receives dense projections from thalamic nuclei sensitive to the wake-promoting neuropeptides orexins, and its deepest part, layer VIb, is the only cortical lamina reactive to orexins. This convergence of wake-promoting inputs prompted us to investigate how layer VIb can modulate cortical arousal, using patch-clamp recordings and optogenetics in rat brain slices.

Glutamate receptors of the delta family are widely expressed in the adult brain.

Recent reports point to critical roles of glutamate receptor subunit delta2 (GluD2) at excitatory synapses and link GluD1 gene alteration to schizophrenia but the expression patterns of these subunits in the brain remain almost uncharacterized. We examined the distribution of GluD1-2 mRNAs and proteins in the adult rodent brain, focusing mainly on GluD1. In situ hybridization revealed widespread neuronal expression of the GluD1 mRNA, with higher levels occurring in several forebrain regions and lower levels in cerebellum.

Development and evaluation of omeprazole pellets fabricated by sieving-spheronization and extrusion - spheronization process.

Pelletized dosage forms can be prepared by different methods which, in general, are time consuming and labor intensive. The current study was carried out to investigate the feasibility of preparing the spherical pellets of omeprazole by sieving-spheronization. An optimized formulation was also prepared by extrusion-spheronization process to compare the physical parameters between these two methods.

Nicotine consumption is regulated by a human polymorphism in dopamine neurons.

Smoking is the most important preventable cause of morbidity and mortality worldwide. Recent genome-wide association studies highlighted a human haplotype on chromosome 15 underlying the risk for tobacco dependence and lung cancer. Several polymorphisms in the CHRNA3-CHRNA5-CHRNB4 cluster coding for the nicotinic acetylcholine receptor (nAChR) α3, α5 and β4 subunits were implicated.

Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement.

Smoking is the most important preventable cause of mortality and morbidity worldwide. This nicotine addiction is mediated through the nicotinic acetylcholine receptor (nAChR), expressed on most neurons, and also many other organs in the body. Even within the ventral tegmental area (VTA), the key brain area responsible for the reinforcing properties of all drugs of abuse, nicotine acts on several different cell types and afferents.

Effects of tocotrienol supplementation on hair growth in human volunteers.

Studies have shown an association between oxidative stress and alopecia. Patients with alopecia generally exhibit lower levels of antioxidants in their scalp area as well as a higher lipid peroxidation index. Tocotrienols belong to the vitamin E family and are known to be potent antioxidants.

Bioequivalence study of generic acyclovir compared with the brand name acyclovir.

Unlabelled: The bioequivalence study of 200-mg generic acyclovir was conducted in healthy males. The reference Zovirax and the test Zevin were administered as a single oral dose after an overnight fast in a two-period, crossover design separated by 1 week. Serial blood samples were collected over a period of 24 hours.