Enhanced firing of locus coeruleus neurons and SK channel dysfunction are conserved in distinct models of prodromal Parkinson's disease.

Parkinson's disease (PD) is clinically defined by the presence of the cardinal motor symptoms, which are associated with a loss of dopaminergic nigrostriatal neurons in the substantia nigra pars compacta (SNpc). While SNpc neurons serve as the prototypical cell-type to study cellular vulnerability in PD, there is an unmet need to extent our efforts to other neurons at risk. The noradrenergic locus coeruleus (LC) represents one of the first brain structures affected in Parkinson's disease (PD) and plays not only a crucial role for the evolving non-motor symptomatology, but it is also believed to contribute to disease progression by efferent noradrenergic deficiency.

A53T-α-synuclein overexpression in murine locus coeruleus induces Parkinson's disease-like pathology in neurons and glia.

Degeneration of noradrenergic locus coeruleus neurons occurs during the prodromal phase of Parkinson's disease and contributes to a variety of non-motor symptoms, e.g. depression, anxiety and REM sleep behavior disorder.

Impaired learning and memory in CD38 null mutant mice.

CD38 is an enzyme that catalyzes the formation of cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate, both of which are involved in the mobilization of Ca(2+) from intracellular stores. Recently, CD38 has been shown to regulate oxytocin release from hypothalamic neurons. Importantly, CD38 mutations are associated with autism spectrum disorders (ASD) and CD38 knockout (CD38(-/-)) mice display ASD-like behavioral phenotypes including deficient parental behavior and poor social recognition memory.

Genetic enhancement of behavioral itch responses in mice lacking phosphoinositide 3-kinase-γ (PI3Kγ).

Phosphoinositide 3-kinases (PI3Ks) are important for synaptic plasticity and various brain functions. The only class IB isoform of PI3K, PI3Kγ, has received the most attention due to its unique roles in synaptic plasticity and cognition. However, the potential role of PI3Kγ in sensory transmission, such as pain and itch has not been examined.