Every moment, organisms must make behavioral decisions that optimize survival and fitness based on internal state cues and external environmental cues. The Barber Lab focuses on key survival behaviors driven by a protohypothalamic region in the fly brain called the pars intercerebralis. How do neurons within the pars intercerebralis sense internal state cues like hunger, tiredness, and time of day? How do neurons within the pars intercerebralis sense environmental cues like food availability and taste? And finally, when multiple conflicting cues arrive in the brain, how are signals integrated to allow the fly to select from mutually exclusive behaviors?
If you’re interested in understanding the biological basis of complex behaviors at the molecular, cellular, and circuit levels - join us!
High throughput behavioral assays
Closed Cortical Crush Injury
Untangling neuropeptide and fast neurotransmitter signaling in a defined circuit
Neural circuits use a combination of classical fast neurotransmitters and modulatory peptide neurotransmitters to communicate. The clock circuit uses both types of signals to influence the circadian timing of sleep, feeding, and locomotion. This project will use a combination of behavioral genetics and classical biochemical methods to understand how the circadian clock uses signals to output brain regions that drive locomotor and feeding behavior.
Integration of internal state and external environmental cues at the circuit level
Organisms must make behavioral decisions based on an array of both internal state cues (like hunger or time of day) and external environmental cues (like availability of food or temperature). The Drosophila pars intercerebralis is a “hub” brain region that receives information about both state and environmental cues, and then releases an array of neuropeptides that influence fly behavior. This project will investigate how diverse signals integrate within the PI at the molecular and electrophysiological levels to influence behavioral choice.
Now recruiting graduate and postdocs.
If you’re interested in understanding the biological basis of complex behaviors at the molecular, cellular and circuit levels - join us! Email email@example.com for details.
Waksman Institute of Microbiology
190 Frelinghuysen Road
Piscataway, NJ 08854
Drosophila clock cells use multiple mechanisms to transmit time-of-day signals in the brain.
Barber AF, Fong SY, Kolesnik A, Fetchko M, Sehgal A. (2021) Drosophila clock cells use multiple mechanisms to transmit time-of-day signals in the brain. Proc Nat Acad Sci USA 118: e2019826118.
Regulation of circadian behavior and physiology by the Drosophila brain clock requires communication from central clock neurons to downstream output regions, but the mechanism by which clock cells regulate downstream targets is not known. We show here that the pars intercerebralis (PI), previously identified as a target of the morning cells in the clock network, also receives input from evening cells. We determined that morning and evening clock neurons have time-of-day–dependent connectivity to the PI, which is regulated by specific peptides as well as by fast neurotransmitters. Interestingly, PI cells that secrete the peptide DH44, and control rest:activity rhythms, are inhibited by clock inputs while insulin-producing cells (IPCs) are activated, indicating that the same clock cells can use different mechanisms to drive cycling in output neurons. Inputs of morning cells to IPCs are relevant for the circadian rhythm of feeding, reinforcing the role of the PI as a circadian relay that controls multiple behavioral outputs. Our findings provide mechanisms by which clock neurons signal to nonclock cells to drive rhythms of behavior.
Hugin+ neurons provide a link between sleep homeostat and circadian clock neurons.
Schwarz JE, King AN, Hsu CT, Barber AF and Sehgal A. (2021) Hugin+ neurons provide a link between sleep homeostat and circadian clock neurons. Proc Nat Acad Sci USA 118: e2111183118. DOI: 10.1073/pnas.2111183118
Sleep is controlled by homeostatic mechanisms, which drive sleep after wakefulness, and a circadian clock, which confers the 24-h rhythm of sleep. These processes interact with each other to control the timing of sleep in a daily cycle as well as following sleep deprivation. However, the mechanisms by which they interact are poorly understood. We show here that hugin+ neurons, previously identified as neurons that function downstream of the clock to regulate rhythms of locomotor activity, are also targets of the sleep homeostat. Sleep deprivation decreases activity of hugin+ neurons, likely to suppress circadian-driven activity during recovery sleep, and ablation of hugin+ neurons promotes sleep increases generated by activation of the homeostatic sleep locus, the dorsal fan-shaped body (dFB). Also, mutations in peptides produced by the hugin+ locus increase recovery sleep following deprivation. Transsynaptic mapping reveals that hugin+ neurons feed back onto central clock neurons, which also show decreased activity upon sleep loss, in a Hugin peptide–dependent fashion. We propose that hugin+ neurons integrate circadian and sleep signals to modulate circadian circuitry and regulate the timing of sleep.
Sleep signals are integrated into an output arm of the circadian clock.
King AN, Barber AF, Schwarz J and Sehgal A. Sleep signals are integrated into an output arm of the circadian clock. In Preparation.
Monitoring electrical activity in Drosophila circadian output neurons.
Barber AF and Sehgal A. Monitoring electrical activity in Drosophila circadian output neurons. Methods Mol Biol Invited review, in press. Cell Metabolism 27: 951-953
Preview: Cold temperatures fire up circadian neurons.
Barber AF and Sehgal A. (2018) Preview: Cold temperatures fire up circadian neurons.
A peptidergic circuit links the circadian clock to locomotor activity.
King AN, Barber AF, Smith AE, Dreyer AP, Sitaraman D, Nitabach MN, Cavanaugh DJ, & Sehgal A. (2017). A peptidergic circuit links the circadian clock to locomotor activity. Curr Biol 27: 1915-27
ircadian and feeding cues integrate to drive rhythms of physiology in Drosophila insulin producing cells.
Barber AF, Erion R, Holmes TC and Sehgal A. (2016). Circadian and feeding cues integrate to drive rhythms of physiology in Drosophila insulin producing cells. Genes Dev 30: 2596-2606
Mechanistic Insights into the Modulation of Voltage-Gated Ion Channels by Inhalational Anesthetics
Covarrubias M, Barber AF, Carnevale V, Treptow W, and Eckenhoff, RG. (2015) Mechanistic Insights into the Modulation of Voltage-Gated Ion Channels by Inhalational Anesthetics Biophys J 109: 2003-11
Modulation of a voltage-gated Na+ channel by sevoflurane involves multiple sites and distinct mechanisms.
Barber AF, Carnevale V, Klein ML, Eckenhoff RG, and Covarrubias M. (2014) Modulation of a voltage-gated Na+ channel by sevoflurane involves multiple sites and distinct mechanisms. Proc Natl Acad Sci USA 111: 6726-31
Exploring Volatile General Anesthetic Binding to a Closed Membrane-Bound Bacterial Voltage-Gated Sodium Channel via Computation
Raju SG, Barber AF, Lebard DN, Klein ML and Carnevale V. (2013) Exploring Volatile General Anesthetic Binding to a Closed Membrane-Bound Bacterial Voltage-Gated Sodium Channel via Computation. PLOS Comput Biol 9: e1003090
Hinge-bending motions in the pore domain of a bacterial voltage-gated sodium channel.
Barber AF, Carnevale V, Raju SG, Amaral C, Treptow W and Klein ML (2012) Hinge-bending motions in the pore domain of a bacterial voltage-gated sodium channel. BBA Biomembranes 1818: 2120-25.
Novel activation of voltage gated K+ channels by sevoflurane.
Barber AF, Liang Q, Covarrubias M. (2012) Novel activation of voltage gated K+ channels by sevoflurane. J Biol Chem 287: 40425-32
Molecular mapping of general anesthetic sites in a voltage-gated ion channel.
Barber AF, Liang Q, Amaral C, Treptow W and Covarrubias M. (2011) Molecular mapping of general anesthetic sites in a voltage-gated ion channel. Biophys J 101:1613-22
Dr. Annika Barber
Dr. Annika Barber is an Assistant Professor in the Department of Molecular Biology and Biochemistry and a laboratory director at the Waksman Institute beginning January 2020. Dr. Barber uses the fruit fly, Drosophila melanogaster, to investigate how neuropeptide signaling is involved in integrating a myriad of sensory cues to select behavioral programs. Her work integrates genetics, behavior and neurophysiology.
Dr. Barber got her Bachelor of Science at Bryn Athyn College. She did her doctoral work at Thomas Jefferson University with Manuel Covarrubias, mapping binding sites for inhaled anesthetics in voltage gated ion channels and developing Markov models of how anesthetics impair channel gating. Dr. Barber moved from single cell patch clamp electrophysiology to Drosophila behavior when she started her Postdoctoral Fellowship with Amita Sehgal at the University of Pennsylvania. In her postdoc, Dr. Barber investigated how a circadian output region regulates sleep, feeding and metabolic function. This piqued her interest in understanding the complex interplay of neuropeptides in Drosophila behavioral circuitry.
Former Lab Researchers
Patrick received his BS in Biology from The College of New Jersey, where he worked in the lab of Dr. Wendy Clement on the molecular systematics of the plant genus Viburnum. He has spent the past four years in various laboratory roles, including rearing parasitoid wasps for the New Jersey Department of Agriculture's Beneficial Insects Lab, environmental water testing, and as a technician in the biotech industry. On top of being a research technician in the Barber lab, he is working on his MS in Statistics at Rutgers University, with the intent of combining his research experience and statistical expertise to perform quantitative work in the life sciences.