Neuroscience Program

Leslie Griffith

Nancy Lurie Marks Professor of Neuroscience
Director, Volen National Center for Complex Systems

Research Description

Biochemistry of Behavior

Survival requires that animals interact in appropriate and adaptive ways with their environment. My lab is interested in how the nervous system integrates information and generates behavioral outputs. We study behavior at the biochemical, cellular and organismal levels using Drosophila melanogaster as a model organism.

Flies, like humans, have basic behaviors (such as locomotion and reproductive behaviors) that can be altered by the animal’s internal state or by exposure to external cues. We use video and automated monitoring systems to assess locomotion, circadian rhythms, sleep and courtship. The ability to manipulate the activity and biochemistry of particular neurons with exquisite spatial and temporal control makes Drosophila a powerful system for this type of integrative approach.

At the cellular level we use both imaging and electrophysiology to understand how the activity of neurons is changed by experience and how these changes are translated into behaviors. Imaging of calcium responses in the adult brain in the sleep circuitry has allowed us to understand the effects of neuromodulators and sleep deprivation on neuronal activity. Direct recording from central neurons in larvae and adults allows us to investigate how cellular activity is regulated during ongoing behavior or as a result of learning. At the biochemical level, we are interested in how calcium, a ubiquitous and critical second messenger, transduces information and regulates plasticity. One of the main mechanisms by which calcium acts within the cell is through the activation of calcium-dependent protein kinases such as calcium/calmodulin-dependent protein kinase II (CaMKII). CaMKII homologs have been found in all multicellular organisms that have been examined and have also been found in yeast. In Drosophila, we have shown that CaMKII is required for both behavioral plasticity in courtship learning and for normal synaptic function at the neuromuscular junction. The long-term goal of this research is to understand the signal transduction pathways underlying changes in synaptic structure and function. By starting with a protein kinase, we have been able to identify both upstream (regulators such as CASK, a MAGUK scaffolding protein) and downstream (substrates such as Eag) elements of the pathway.