We are interested in understanding the molecular mechanisms underlying behavioral plasticity on three major time scales:

1. Evolutionary time scale: we use genetic and genomic approaches to understand mechanisms that underlie behavioral variations between individuals as well as between species. These studies will help understand the role of behavioral phenotypes in driving evolution, and the role of behavior in speciation.

2. Developmental time scale: we study mechanisms underlying changes in specific behaviors expressed by single individuals over their lifetime, with specific emphasis on processes that affect neuronal plasticity at the sensory and central levels.

3. Physiological time scale: we study mechanisms underlying changes in behavior in response to acute changes in the physical and social environements of individuals. Here we focus on understanding how behaviorally specific stimuli activate specific neuronal circuits, which results in the release of a specific behavior.

The Ben-Shahar lab studies various projects that are related to one or more of the above processes using insect models. Although we are currently focusing on the powerful genetic model Drosophila melanogaster (the fruit fly), we are also developing projects that will utilize the emerging model for complex social behaviors, the European honey bee, Apis mellifera. Work in our lab is at the interface of behavior, genetics, genomics, molecular and cellular biology, and neurophysiology. We hope these studies will result in an integrative understanding of the mechanisms for behavioral plasticity. Some of the projects currently investigated in the lab are described below.

Sensory functions in the mammalian airway epithelium

In recent years several studies from our lab and others indicate that canonical sensory signaling pathways are also found outside the canonical sensory organs. These findings significantly expand our field of view in terms of what constitutes a sensory cell, and suggest that cell-autonomous reception, independent of the nervous system, is also likely playing an important role in health and disease. Our lab is currently focusing on several projects that use human and rodent airway epithelium to investigate the roles of pulmonary taste and olfactory receptors in diverse physiological systems.

Neuronal functions of Degenerin/ epithelial sodium channels

Degenerin/ epithelial sodium channels (DEG/ENaC) form non-voltage-gated, amiloride-sensitive cation channels. The active Deg/ENaC channel is comprised of three to nine independent subunits. Each subunit has two transmembrane domains, two short intracellular domains and a large extracellular loop, which is a characteristic of the family. The Deg/ENaC family seems to be animal specific and members have been identified in diverse species. Different subunits are enriched in peripheral and central neurons, and several members of the family contribute to mechanosensation, pH sensing, or are activated by peptides, but for most, the physiological function is still unknown. The Drosophila genome encodes for 30 members of the family, which are named pickpocket genes 1-30 (ppk). We use the fly as a model to understand the central and peripheral neuronal roles of these Deg/ENaC subunits with genetic, behavioral, and physiological tools. We are currently investigating the role of multiple family members in processes such as chemosensation, mechanosensation and proprioception, as well as the possible role of some subunits in synaptic plasticity.

FUNDING: (NIH-NIDCD) National Institute on Deafness and other Communication Disorders

The role of brain divalent cation homeostasis in behavioral plasticity

Homeostasis of divalent cations plays an important role in various physiological systems. Evidence suggests that disruptions in this homeostasis can result in neuronal and behavioral phenotypes. We are using Drosophila genetics, physiological tools, and molecular neurobiology to decipher the mechanisms by which metal ion homeostasis is regulated in the nervous system, and the roles metal ions are playing in neuronal physiology and behavior.

FUNDING: The Children Discovery Institute

Post-transcriptional, mRNA dependent regulation of neuronal excitability

Neuronal excitability and physiological homeostasis are tightly regulated processes, which involve the function of diverse ion channels. We investigate the hypothesis that some neuronal properties are regulated via mRNA dependent interactions that specifically regulate the mRNA stability and/or translation efficiency of specific sodium and potassium channels in the nervous system of the fruit fly, Drosophila melanogster.

FUNDING: The Esther A. & Joseph Klingenstein Fund