Topic: D1R

Neuromodulators like dopamine are critical regulators of associative learning. Indeed, dopaminergic neurons in the dorsal tegmental area interact with the lateral central amygdala (CEl) circuitry involved in fear behavior. Thus, fear learning modulates the microcircuit of the CEl composed of somatostatin-positive (SST+) and protein kinase C-positive (PKCδ+) neurons. During this process, dopamine 1 receptor (D1R) activation enables LTP induction in SST+ CEl neurons (Groessl et al. 2018, Nat Neurosci 21:952-962).In fact, a detailed analysis of dopaminergic cellular effects on synaptic transmissi

Incidental learning (IL) can be studied using sensory preconditioning, a higher-order memory process. Incidental associations between low-salience stimuli (e.g. odors, tastes, lights or tones) happen during a preconditioning phase that is followed by classical conditioning of one of these stimuli with an aversive or appetitive unconditioned reinforcer. As a result, subjects present a response to the directly conditioned stimulus but also a mediated response to the preconditioned stimulus never explicitly reinforced, implying initial IL. We performed three different protocols to study IL using

NMDA receptor antagonists, such as MK801, produce hyperlocomotion and affect the dopamine (DA) system by increasing ventral tegmental area (VTA) activity and enhancing DA release in many regions of the rat brain. NMDAR antagonists also enhance the power of high-frequency oscillations (HFO) in cortical and subcortical areas. The olfactory bulb (OB), a generator of NMDAR-enhanced HFO, contains DA receptors (D1R/D2R) and periglomerular DA neurons. However, the role of DA in the OB in the modulation of MK801-enhanced HFO and locomotion is unknown. Selective DA agonists (SKF38393, quinpirole) and a

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to reduced striatal dopamine and motor and non-motor symptoms. The imbalance of adenosine signaling plays a role in the pathogenesis of PD, particularly through increased A2AR and reduced A1R activity affecting D2R and D1R signaling pathways, respectively. This imbalance interferes with the reciprocal modulation of adenylate cyclase by A1R/D1R and A2AR/D2R and impairs motor control. Despite existing treatment options, there is an unmet need for new interve