SUMMARYPurpose: To investigate whether striatal enriched protein tyrosine phosphatase (STEP) influences ictogenesis. Methods: STEP knockout mice were compared to wildtype (WT) mice in pilocarpine-induced seizures. Hippocampal slices were also prepared from these two mouse populations, allowing the examination of ictal-like stimulation in these slices using calcium imaging and electrophysiologic recordings. Key Findings: To examine seizure thresholds, increasing doses of pilocarpine were administered to adult mice and seizures were scored behaviorally. Significantly fewer STEP knockout mice developed seizures that progressed to the stage of status epilepticus compared to WT mice.To examine potential differences in neural circuits that might account for this finding, seizure-like activity was induced in hippocampal slices. Electrical stimulation of the hippocampal-entorhinal cortex pathway in STEP knockout mice resulted in less activation of the dentate gyrus granule cell layer (GCL), but greater activation of the hilus in STEP knockouts, compared with heterozygous slices. Significance: STEP deficiency is associated with higher seizure thresholds. The locus of these effects appears to include the dentate gyrus granule cell layer and hilus.

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The avian brain is a valuable model for exploring adult neurogenesis. Here we use immunohistochemical methods to detect cell division and the incorporation of new neurons in the adult zebra finch brain. The nonradioactive, relatively inexpensive thymidine analog bromodeoxyuridine (BrdU) is used to label replicating DNA in dividing cells. The brain is harvested, fixed, and dehydrated before being embedded in polyethylene glycol (PEG), which results in superior histology compared to frozen specimens. After the PEG-embedded brain tissue is sectioned and mounted on slides, standard immunohistochemical procedures are used to detect both BrdU and the neuron-specific marker Hu. MATERIALS

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The recipe entitled "Phosphate-Buffered Saline (PBS; 0.1 M, pH 7.4)" was incorrect when this protocol was first published. The correct version of the recipe is below. In addition, the HTML version of the recipe and the PDF version of the protocol have been amended accordingly. The authors apologize for any confusion that arose from this error. Phosphate-Buffered Saline (PBS; 0.1 M, pH 7.4) 80 g NaCl 2.0 g KCl 21.7 g Na 2 HPO 4 • 7H 2 O 2.59 g KH 2 PO 4 Prepare in 1 L of ddH 2 O.