Potentiating KCC2 activity is sufficient to limit the onset and severity of seizures.

The type 2 K/Cl cotransporter (KCC2) allows neurons to maintain low intracellular levels of Cl, a prerequisite for efficient synaptic inhibition. Reductions in KCC2 activity are evident in epilepsy; however, whether these deficits directly contribute to the underlying pathophysiology remains controversial. To address this issue, we created knock-in mice in which threonines 906 and 1007 within KCC2 have been mutated to alanines (KCC2-T906A/T1007A), which prevents its phospho-dependent inactivation.

Restriction of dietary protein leads to conditioned protein preference and elevated palatability of protein-containing food in rats.

The mechanisms by which intake of dietary protein is regulated are poorly understood despite their potential involvement in determining food choice and appetite. In particular, it is unclear whether protein deficiency results in a specific appetite for protein and whether influences on diet are immediate or develop over time. To determine the effects of protein restriction on consumption, preference, and palatability for protein we assessed patterns of intake for casein (protein) and maltodextrin (carbohydrate) solutions in adult rats.

Characterization of a 32 μm diameter carbon fiber electrode for in vivo fast-scan cyclic voltammetry.

Carbon fiber electrodes (CFE) are commonly used for in vivo detection of catecholamines due to their excellent electrochemical properties and biocompatibility. Fast-scan cyclic voltammetry (FSCV) combined with CFEs permits the detection of catecholamines such as dopamine (DA) with high specificity and reliability. However, advances in neuroscience constantly demand sensors with greater sensitivities and selectivities.

Methylphenidate modifies overflow and presynaptic compartmentalization of dopamine via an α-synuclein-dependent mechanism.

Methylphenidate (MPD) modulates dopamine (DA) overflow in part by redistributing vesicle pools, a function shared by the presynaptic protein α-synuclein (α-syn). We suggest that α-syn modifies the effect of MPD on DA neurotransmission. The effect was studied in the dorsal striatum in wild-type mice and two mouse lines lacking α-syn by using in vivo voltammetry and microdialysis.

Sub-regional differences and mechanisms of the short-term plasticity of dopamine overflow in striatum in mice lacking alpha-synuclein.

Mice lacking the pre-synaptic protein alpha-synuclein (α-syn) demonstrate enhanced facilitation of dopamine (DA) overflow in dorsal striatum following repeated, high-frequency burst stimulation of the dopaminergic pathways. Dorsal striatum is most vulnerable to neurodegeneration in Parkinson's disease. The role of α-syn in facilitation of DA overflow in the ventral striatum, which is less vulnerable to neurodegeneration, is unknown.

Decreased reuptake of dopamine in the dorsal striatum in the absence of α-synuclein.

The presynaptic protein alpha-synuclein (α-syn) plays a role in dopaminergic neurotransmission in the nigrostriatal dopaminergic system. Mutations in this protein have been linked to pathogenesis of Parkinson's disease. However, the details of regulation of dopamine homeostasis by α-syn and its molecular targets are generally unknown.