Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions.

Purpose: Diagnostic exome sequencing was immediately successful in diagnosing patients in whom traditional technologies were uninformative. Herein, we provide the results from the first 500 probands referred to a clinical laboratory for diagnostic exome sequencing.

Methods: Family-based exome sequencing included whole-exome sequencing followed by family inheritance-based model filtering, comprehensive medical review, familial cosegregation analysis, and analysis of novel genes.

Activity-dependent inhibitory gating in molecular signaling cascades induces a novel form of intermediate-term synaptic facilitation in Aplysia californica.

Mechanistically distinct forms of long-lasting plasticity and memory can be induced by a variety of different training patterns. Although several studies have identified distinct molecular pathways that are engaged during these different training patterns, relatively little work has explored potential interactions between pathways when they are simultaneously engaged in the same neurons and circuits during memory formation. Aplysia californica exhibits two forms of intermediate-term synaptic facilitation (ITF) in response to two different training patterns: (1) repeated trial (RT) ITF (induced by repeated tail nerve shocks [TNSs] or repeated serotonin [5HT] application) and (2) activity-dependent (AD) ITF (induced by sensory neuron activation paired with a single TNS or 5HT pulse).

MicroRNAs in memory processing.

MicroRNAs are a class of small RNA molecules that regulate the expression of a wide variety of genes. In this issue of Neuron, Rajasethupathy and colleagues identify 170 distinct microRNAs in Aplysia, including one, miR-124, that plays a critical role in the regulation of signaling molecules underlying synaptic plasticity and memory.