Homeostatic regulation of extracellular signal-regulated kinase 1/2 activity and axonal K7.3 expression by prolonged blockade of hippocampal neuronal activity.

Homeostatic plasticity encompasses the mechanisms by which neurons stabilize their synaptic strength and excitability in response to prolonged and destabilizing changes in their network activity. Prolonged activity blockade leads to homeostatic scaling of action potential (AP) firing rate in hippocampal neurons in part by decreased activity of N-Methyl-D-Aspartate receptors and subsequent transcriptional down-regulation of potassium channel genes including which encodes K7.3.

Pharmacological inhibition of STriatal-Enriched protein tyrosine Phosphatase by TC-2153 reduces hippocampal excitability and seizure propensity.

Objective: STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific tyrosine phosphatase. Membrane-bound STEP is the only isoform expressed in hippocampus and cortex. Genetic deletion of STEP enhances excitatory synaptic currents and long-term potentiation in the hippocampus.

The Role of K7 Channels in Neural Plasticity and Behavior.

Activity-dependent persistent changes in neuronal intrinsic excitability and synaptic strength are widely thought to underlie learning and memory. Voltage-gated KCNQ/K7 potassium channels have been of great interest as the potential targets for memory disorders due to the beneficial effects of their antagonists in cognition. Importantly, dominant mutations in their neuronal subunits /K7.

Counting growth factors in single cells with infrared quantum dots to measure discrete stimulation distributions.

The distribution of single-cell properties across a population of cells can be measured using diverse tools, but no technology directly quantifies the biochemical stimulation events regulating these properties. Here we report digital counting of growth factors in single cells using fluorescent quantum dots and calibrated three-dimensional deconvolution microscopy (QDC-3DM) to reveal physiologically relevant cell stimulation distributions. We calibrate the fluorescence intensities of individual compact quantum dots labeled with epidermal growth factor (EGF) and demonstrate the necessity of near-infrared emission to overcome intrinsic cellular autofluoresence at the single-molecule level.

The brain-derived neurotrophic factor VAL68MET polymorphism modulates how developmental ethanol exposure impacts the hippocampus.

Prenatal exposure to alcohol causes a wide range of deficits known as fetal alcohol spectrum disorders (FASDs). Many factors determine vulnerability to developmental alcohol exposure including timing and pattern of exposure, nutrition and genetics. Here, we characterized how a prevalent single nucleotide polymorphism in the human brain-derived neurotrophic factor (BDNF) gene (val66met) modulates FASDs severity.