Nicotinic acetylcholine receptors

…Nicotine binds highly to the nicotinic acetylcholine receptors (nAChRs) in the habenula, perturbing cholinergic signaling. The evolutionary conserved habenula contains the largest density of nAChRs and is known as the aversive brain due to its role in mediating stress, fear and anxiety. Our research aims to understand how cholinergic signaling modulates the activity and function of the habenula. For this aim, we have generated zebra

Striatal dopamine (DA) and acetylcholine (ACh) play key roles in reward prediction signalling and goal-directed behaviour. Midbrain DA neurons increase their firing in response to unexpected rewards or reward-predicting cues, while striatal cholinergic interneurons exhibit coincident burst-pause activity. Striatal DA and ACh also reciprocally regulate each other’s release with ACh modulating DA release through axonal nicotinic acetylcholine receptors (nAChRs). Activation of nAChRs can drive DA release but also generate strong short-term depression (STD) of subsequent DA release, not arising fr

Nicotinic acetylcholine receptors (nAChRs) are widely expressed throughout the brain and they are involved in the control of fundamental neural functions. One of the most common nAChR subtypes are heteromeric beta2-containing (beta2*) nAChRs. In the prefrontal cortex (PFC), beta2* nAChRs are expressed by different neuronal populations with different effects on behavior. To better understand functional role of beta2* nAChRs, we need to know which neuronal types in the PFC express them and what is the effect of these receptors on behavior. In the present project, we used FISH to map the expressi

Nicotinic acetylcholine receptors (nAChRs) are pentameric ionotropic receptors composed of a combination of α and β subunits. Human genetic association and preclinical studies have shown a key role of α5 containing nAChRs (α5*nAChRs) in the risk to develop nicotine addiction. Tobacco smoking is highly comorbid with bulimia nervosa and binge eating disorders. Interestingly, genetic variation at CHRNA5 has also been associated with higher body mass index (BMI) in never smokers, but lower BMI in current smokers, and increased appetence for food in rodents. Here we sought to investigate the role o

…Cholinergic neurons, which release acetylcholine (ACh), are known to enhance attention and their pathophysiology is associated with disorders such as Alzheimer’s disease and epilepsy. Nicotinic acetylcholine receptors (nAChRs) are activated by the cholinergic system and modulate neuronal excitability. Therefore, understanding nAChR mediated synaptic neurotransmission will allow us to better understand how the activity of neurons are precisely controlled

Astrocytes are key supporters of brain functioning that are well documented to influence neural circuits over slow and prolonged timescales. Astrocytes in striatum regulate the extracellular neuromodulator landscape that governs dopamine transmission. We explored whether striatal astrocytes might act dynamically within striatal circuits to govern dopamine function. Surprisingly, we show that striatal astrocytes rapidly modulate dopamine release on a subsecond timescale. Brief optogenetic depolarisation of striatal astrocytes in mouse ex vivo brain slices strongly and reversibly modulated dopam

…Nicotinic acetylcholine receptors (nAChRs) in the brain play a crucial role in vasodilation in the neocortex induced by basal forebrain cholinergic activation or nicotine injection. Information about the sense of smell is conveyed by the olfactory nerve, or by the intranasal trigeminal nerve when irritating odors. We recently reported that nicotine potentiates the olfactory bulb vasodilation induced by olfactory nerv

Rhythmic electrical activity in the central nervous system is involved in cognitive functions in many animals and is also found in the olfactory centers of terrestrial gastropods, including slugs and snails. The procerebrum, the secondary olfactory center of the terrestrial slug (Limax valentianus), forms a unique layered structure that generates spontaneous, synchronized oscillatory activity all the time to process odor-related information. Previous studies have shown that synchronous oscillatory networks are spontaneously reorganized as neurites elongate in dispersed cell culture of procereb

The striatum is densely innervated by midbrain dopamine (DA) neurons but also receives a further sparse monoaminergic innervation by raphe serotonin (5-HT) neurons. Striatal 5-HT has been suggested to have some opposing functions to DA but also to regulate DA release which might support (or counteract) this functional antagonism. We explored the reciprocal modulation of electrically evoked striatal DA and 5-HT release and the underlying cell circuits by using fast-scan cyclic voltammetry to detect DA, a new G-protein-coupled receptor sensor for 5-HT (GRAB5-HT3.0) and whole-cell recordings in a

…of cholinergic neurons containing the nicotinic acetylcholine receptors (nAChR). NAChR agonists protect neuronal cells against amyloid toxicity, eliminate the senile plaques, and improve learning and memory of transgenic mice. Moreover, nAChRs antagonists, that block the binding of Abeta to the receptor, inhibit Abeta-induced tau protein phosphorylation in neuronal cells. It means that the toxicity of Aβ is mediated through a direct interaction between Abeta and nAChRs. The most abun

Although bradykinesia, tremor, and rigidity are hallmark motor defects in Parkinson’s disease (PD) patients, they also experience motor learning impairments and non-motor symptoms such as depression. The neural basis for these different PD symptoms are not well understood. While current treatments are effective for locomotion deficits in PD, therapeutic strategies targeting motor learning deficits and non-motor symptoms are lacking. We found that distinct parafascicular (PF) thalamic subpopulations project to caudate putamen (CPu), subthalamic nucleus (STN), and nucleus accumbens (NAc). While